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NCT00467428
|
Efficacy and Safety of NS2359 in Adults With Attention Deficit Hyperactivity Disorder
|
The purpose of the study is to investigate if NS2359 is effective in the treatment of ADHD in adult patients.
|
Efficacy and Safety of NS2359 in Adults With Attention Deficit Hyperactivity Disorder. A Randomised, Double-Blind, Placebo-Controlled Study
|
Attention Deficit Hyperactivity Disorder
|
* Drug: NS2359
* Drug: Placebo
|
Inclusion Criteria:~Patients with the diagnosis of Attention Deficit Hyperactivity Disorder (ADHD), by DSM-IV, as manifested in clinical evaluation and confirmed by structured interview using the K-SADS-E adult ADHD module~Patients with a CGI Global Severity (GS) score ≥4 (moderate impairment)~The Patient provided written informed consent.~Non-lactating women of childbearing potential that used adequate contraception (i.e. the use of oral contraceptives and practising a double-barrier form of birth control) and had a negative pregnancy test at screening. Women of no childbearing potential who had been postmenopausal for less than 2 years must have a negative pregnancy test at screening.~Exclusion Criteria:~Any clinically unstable medical condition~Clinically significant abnormal baseline laboratory values~Mental retardation~Organic brain disorders~Non-febrile seizure disorder~Patients with a history of an eating disorder including anorexia or bulimia nervosa~Psychotic disorder of any type~Patients with a HAM-D (17 item) >15~Patients currently (within the past 6 months) known to abuse or to be dependent on any drug, including alcohol or a positive urine drug screen for cocaine, heroin, or marijuana~Treatment with stimulants was prohibited within 1 week prior to randomisation~Treatment with antipsychotics/neuroleptics was prohibited for 8 weeks prior to randomisation~Treatment with monoamine oxidase inhibitors was prohibited for 8 weeks prior to randomisation~Treatment with tricyclic antidepressants, histamines and selective serotonin reuptake inhibitors was prohibited for 4 weeks (fluoxetine for 6 weeks) prior to randomisation~Treatment with benzodiazepines, anticonvulsants (for behaviour) and lithium for 2 weeks prior to randomisation~Patients with a history of bipolar disorder~Patients using any concurrent medication for the treatment of ADHD~Patients that had previously participated in a NS2359 study~Patients treated with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication~Patients with a history of positive human immunodeficiency virus (HIV) test.
|
18 Years
|
55 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To investigate the efficacy of NS2359 in adult patients diagnosed with ADHD (predominantly inattentive, predominantly hyperactive/impulsive or combined) according to DSM-IV criteria. | | |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To investigate the safety and tolerability of NS2359 in adult ADHD patients. | | |
|
ADHD
|
Hyperkinesis, Attention Deficit Disorder with Hyperactivity, Attention Deficit and Disruptive Behavior Disorders, Neurodevelopmental Disorders, Mental Disorders, Dyskinesias, Neurologic Manifestations, Nervous System Diseases
|
| Intervention/Treatment |
| --- |
|Drug: NS2359|nan|
|Drug: Placebo|nan|
|
Efficacy and Safety of NS2359 in Adults With Attention Deficit Hyperactivity Disorder
Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to investigate if NS2359 is effective in the treatment of ADHD in adult patients.
Official Title
-----------------
Efficacy and Safety of NS2359 in Adults With Attention Deficit Hyperactivity Disorder. A Randomised, Double-Blind, Placebo-Controlled Study
Conditions
-----------------
Attention Deficit Hyperactivity Disorder
Intervention / Treatment
-----------------
* Drug: NS2359
* Drug: Placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with the diagnosis of Attention Deficit Hyperactivity Disorder (ADHD), by DSM-IV, as manifested in clinical evaluation and confirmed by structured interview using the K-SADS-E adult ADHD module Patients with a CGI Global Severity (GS) score ≥4 (moderate impairment) The Patient provided written informed consent. Non-lactating women of childbearing potential that used adequate contraception (i.e. the use of oral contraceptives and practising a double-barrier form of birth control) and had a negative pregnancy test at screening. Women of no childbearing potential who had been postmenopausal for less than 2 years must have a negative pregnancy test at screening. Exclusion Criteria: Any clinically unstable medical condition Clinically significant abnormal baseline laboratory values Mental retardation Organic brain disorders Non-febrile seizure disorder Patients with a history of an eating disorder including anorexia or bulimia nervosa Psychotic disorder of any type Patients with a HAM-D (17 item) >15 Patients currently (within the past 6 months) known to abuse or to be dependent on any drug, including alcohol or a positive urine drug screen for cocaine, heroin, or marijuana Treatment with stimulants was prohibited within 1 week prior to randomisation Treatment with antipsychotics/neuroleptics was prohibited for 8 weeks prior to randomisation Treatment with monoamine oxidase inhibitors was prohibited for 8 weeks prior to randomisation Treatment with tricyclic antidepressants, histamines and selective serotonin reuptake inhibitors was prohibited for 4 weeks (fluoxetine for 6 weeks) prior to randomisation Treatment with benzodiazepines, anticonvulsants (for behaviour) and lithium for 2 weeks prior to randomisation Patients with a history of bipolar disorder Patients using any concurrent medication for the treatment of ADHD Patients that had previously participated in a NS2359 study Patients treated with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication Patients with a history of positive human immunodeficiency virus (HIV) test.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Arms and Interventions
| Intervention/Treatment |
| --- |
|Drug: NS2359|nan|
|Drug: Placebo|nan|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To investigate the efficacy of NS2359 in adult patients diagnosed with ADHD (predominantly inattentive, predominantly hyperactive/impulsive or combined) according to DSM-IV criteria. | | |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To investigate the safety and tolerability of NS2359 in adult ADHD patients. | | |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ADHD
|
|
NCT03035981
|
Gastric Emptying of Rice With Different Starch Properties
|
Glycemic carbohydrates are associated with metabolic disturbances, such as type II diabetes, due to rapid digestion of starch into glucose. The specific properties of starch within these foods has been studied for the purpose of slowing their digestion rate and improving related physiological outcomes, such as gastric emptying rate. The current study investigated the relationship among starch digestion, gastric emptying rate and satiety in white and brown rice.
|
Studies have indicated that starch-based foods with somewhat high amylose content have slower in vitro starch digestion rates, which relate to a low glycemic response. Low glycemic response is associated with delayed gastric emptying rate as well. Therefore, we hypothesized that rice with a slow starch digesting property would delay gastric emptying. White and brown rice with varying amylose contents were used in this study. A 13C-labeled octanoic acid breath test method was used to measure gastric emptying rate, and questionnaires were used to assess hunger and fullness during the testing sessions. Twelve healthy volunteers were recruited to participate in a crossover design study with six rice treatments and outcome measurements were gastric emptying and satiety assessments. One fermentable carbohydrate (fructooligosaccharide, FOS) solution was used to validate the production of breath hydrogen.
|
Assessment of Gastric Emptying and Fullness of Rice With Different Starch Properties
|
Appetitive Behavior
|
* Other: White rice, low amylose
* Other: White rice, high amylose
* Other: White rice, slow
* Other: White rice, resistant
* Other: Brown rice, low amylose
* Other: Brown rice, high amylose
* Other: Fructooligosaccharide (FOS)
|
Inclusion Criteria:~Normal body mass index (18 kg/m2 ≤ BMI ≤ 25 kg/m2)~Exclusion Criteria:~Under any medication~History of any gastrointestinal disease or surgery~Diabetes~Smoker
|
18 Years
|
50 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gastric emptying | Breath test was performed using 13C-octanoic acid mixed into test meals | Acute study, 4 hours after consumption of test food |
| Appetitive response | Fullness and hunger questionnaire was given at various time points after consumption of test foods | Acute study, 4 hours after consumption of test food |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Breath hydrogen | Hydrogen breath test was performed following ingestion of test meals | Acute study, 4 hours after consumption of test food |
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: White rice, low amylose<br>Cooked white rice with low amylose content | Other: White rice, low amylose<br>* White and brown rice were tested for differences in gastric emptying rate and appetitive response<br>|
| Experimental: White rice, high amylose<br>Cooked white rice with high amylose content | Other: White rice, high amylose<br>* White and brown rice were tested for differences in gastric emptying rate and appetitive response<br>|
| Experimental: White rice, slow<br>Cooked white rice with slow digesting starch | Other: White rice, slow<br>* White and brown rice were tested for differences in gastric emptying rate and appetitive response<br>|
| Experimental: White rice, resistant<br>Cooked white rice with resistant starch | Other: White rice, resistant<br>* White and brown rice were tested for differences in gastric emptying rate and appetitive response<br>|
| Experimental: Brown rice, low amylose<br>Cooked brown rice with low amylose content | Other: Brown rice, low amylose<br>* White and brown rice were tested for differences in gastric emptying rate and appetitive response<br>|
| Experimental: Brown rice, high amylose<br>Cooked brown rice with high amylose content | Other: Brown rice, high amylose<br>* White and brown rice were tested for differences in gastric emptying rate and appetitive response<br>|
| Experimental: Fructooligosaccharide (FOS)<br>Fermentable carbohydrate solution | Other: Fructooligosaccharide (FOS)<br>* White and brown rice were tested for differences in gastric emptying rate and appetitive response<br>|
|
Gastric Emptying of Rice With Different Starch Properties
Study Overview
=================
Brief Summary
-----------------
Glycemic carbohydrates are associated with metabolic disturbances, such as type II diabetes, due to rapid digestion of starch into glucose. The specific properties of starch within these foods has been studied for the purpose of slowing their digestion rate and improving related physiological outcomes, such as gastric emptying rate. The current study investigated the relationship among starch digestion, gastric emptying rate and satiety in white and brown rice.
Detailed Description
-----------------
Studies have indicated that starch-based foods with somewhat high amylose content have slower in vitro starch digestion rates, which relate to a low glycemic response. Low glycemic response is associated with delayed gastric emptying rate as well. Therefore, we hypothesized that rice with a slow starch digesting property would delay gastric emptying. White and brown rice with varying amylose contents were used in this study. A 13C-labeled octanoic acid breath test method was used to measure gastric emptying rate, and questionnaires were used to assess hunger and fullness during the testing sessions. Twelve healthy volunteers were recruited to participate in a crossover design study with six rice treatments and outcome measurements were gastric emptying and satiety assessments. One fermentable carbohydrate (fructooligosaccharide, FOS) solution was used to validate the production of breath hydrogen.
Official Title
-----------------
Assessment of Gastric Emptying and Fullness of Rice With Different Starch Properties
Conditions
-----------------
Appetitive Behavior
Intervention / Treatment
-----------------
* Other: White rice, low amylose
* Other: White rice, high amylose
* Other: White rice, slow
* Other: White rice, resistant
* Other: Brown rice, low amylose
* Other: Brown rice, high amylose
* Other: Fructooligosaccharide (FOS)
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Normal body mass index (18 kg/m2 ≤ BMI ≤ 25 kg/m2) Exclusion Criteria: Under any medication History of any gastrointestinal disease or surgery Diabetes Smoker
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: White rice, low amylose<br>Cooked white rice with low amylose content | Other: White rice, low amylose<br>* White and brown rice were tested for differences in gastric emptying rate and appetitive response<br>|
| Experimental: White rice, high amylose<br>Cooked white rice with high amylose content | Other: White rice, high amylose<br>* White and brown rice were tested for differences in gastric emptying rate and appetitive response<br>|
| Experimental: White rice, slow<br>Cooked white rice with slow digesting starch | Other: White rice, slow<br>* White and brown rice were tested for differences in gastric emptying rate and appetitive response<br>|
| Experimental: White rice, resistant<br>Cooked white rice with resistant starch | Other: White rice, resistant<br>* White and brown rice were tested for differences in gastric emptying rate and appetitive response<br>|
| Experimental: Brown rice, low amylose<br>Cooked brown rice with low amylose content | Other: Brown rice, low amylose<br>* White and brown rice were tested for differences in gastric emptying rate and appetitive response<br>|
| Experimental: Brown rice, high amylose<br>Cooked brown rice with high amylose content | Other: Brown rice, high amylose<br>* White and brown rice were tested for differences in gastric emptying rate and appetitive response<br>|
| Experimental: Fructooligosaccharide (FOS)<br>Fermentable carbohydrate solution | Other: Fructooligosaccharide (FOS)<br>* White and brown rice were tested for differences in gastric emptying rate and appetitive response<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gastric emptying | Breath test was performed using 13C-octanoic acid mixed into test meals | Acute study, 4 hours after consumption of test food |
| Appetitive response | Fullness and hunger questionnaire was given at various time points after consumption of test foods | Acute study, 4 hours after consumption of test food |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Breath hydrogen | Hydrogen breath test was performed following ingestion of test meals | Acute study, 4 hours after consumption of test food |
|
||
NCT05588466
|
Practice Facilitation to Scale up a CDS for Hypertension Management
|
Hypertension (HTN) is the most prevalent modifiable risk factor for cardiovascular disease among U.S. adults. Despite a long history of established guidelines to support clinical management, only half of U.S. adults diagnosed with HTN have poorly controlled blood pressure (BP) and medication adherence to proven effective treatment remains suboptimal. Clinical decision support (CDS) has the potential to overcome barriers to delivering guideline-recommended care and improve HTN management. Practice facilitation is a well-demonstrated implementation strategy to support process changes and has the potential to facilitate CDS implementation. Our objective is to rigorously evaluate whether practice facilitation provided in concert with a HTN-focused CDS that incorporates medication adherence results is an effective strategy for scaling and implementing CDS. The investigators will update an existing CDS to incorporate alerts and tools to address medication adherence then randomize 40 small independent primary care practices in New York City to receive either practice facilitation in addition to the CDS or the CDS alone. After a twelve-month intervention period, The investigators will examine the differences in blood pressure control achieved by practices in the CDS plus practice facilitation group versus practices that received the CDS alone
|
Hypertension (HTN) is the most prevalent modifiable risk factor for cardiovascular disease among U.S. adults. Despite a long history of established guidelines to support clinical management, only half of U.S. adults diagnosed with HTN have poorly controlled blood pressure (BP) and medication adherence to proven effective treatment remains suboptimal. Clinical decision support (CDS) has the potential to overcome barriers to delivering guideline-recommended care and improve HTN management. However, optimal strategies for scaling CDS have not been well established, particularly in small independent primary care practices which often lack the resources to effectively change practice routines in order to effectively utilize CDS. Further, CDS is used in relatively few components of the medication management process, despite indications that CDS alerts are likely to impact patient care. Practice facilitation is a well-demonstrated implementation strategy to support process changes and has the potential to facilitate CDS implementation. Our objective is to rigorously evaluate whether practice facilitation provided in concert with a HTN-focused CDS that incorporates medication adherence results is an effective strategy for scaling and implementing CDS. The investigators will initially update and incorporate an evidence-based hypertension-focused CDS shown to be effective in Federally Qualified Health Centers (FQHCs) into an existing commercial electronic health record (EHR) system used by a large network of independent primary care practices. This CDS will employ several features shown to be effective in the FQHCs, including passive alerts, order sets, documentation templates, standardized medication adherence questionnaires, and clinical reminders. Additionally, the CDS will incorporate a new feature, a medication adherence alert based on prescription claims data. The investigators will then randomize 40 small independent primary care practices in New York City to receive either practice facilitation in addition to the CDS or the CDS alone. The PF intervention will include an initial training in the CDS and review of current guidelines along with follow-up in-person and remote meetings for coaching and supporting integration into the workflow. After a twelve-month intervention period, The investigators will examine the differences in blood pressure control achieved by practices in the CDS plus practice facilitation group versus practices that received the CDS alone. The investigators will also assess the implementation process for scaling the CDS using the RE-AIM framework. The results of this study will inform future efforts to implement and scale CDS into small primary care practices, where much of care delivery occurs in the U.S.
|
Assessing the Use of Practice Facilitation to Optimize Scale up of CDS for Hypertension
|
Hypertension
|
* Other: CDS Alone
* Other: CDS plus practice facilitation
|
Inclusion Criteria:~18-85 years old~an outpatient clinic visit with an HTN diagnosis based on the ICD-10 code in the prior 12 months~must have received care at the clinic for at least 12 months~Exclusion Criteria:~not pregnant~not have end-stage kidney disease as defined by an ICD-10 code for dialysis or transplantation
|
18 Years
|
85 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients who had a diagnosis of hypertension (HTN) and whose blood pressure (BP) was adequately controlled using BP documented in the electronic health record | The primary outcome will be a measure of clinical effectiveness, or the percentage of patients who have achieved BP control, defined as BP <140/90 mmHg in the mean of the last two EHR-recorded measurements during each of the pre-intervention and post-intervention study periods. | 12-months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in average systolic and diastolic blood pressure (mmHg) of patients who had a diagnosis of hypertension (HTN) using BP documented in the electronic health record | A secondary measure will be the average change in systolic and diastolic BP (mmHg) of patients who had a diagnosis of HTN between the pre- and post-intervention period. | 12-months |
| Percentage of patients who had a diagnosis of hypertension (HTN) and a documented blood pressure (BP)-lowering medication and whose calculated medication adherence rate is considered adherent using pharmacy claims data | A secondary outcome will be percentage of patients who had a diagnosis of HTN and a documented BP-lowering medication and whose calculated medication adherence rate is considered adherent pre- and post-intervention period. Adherence is measured as proportion of days covered (PDC) where a PDC >80% is considered adherent. PDC is calculated using prescription fill data from pharmacy claims. | 12-months |
|
Clinical Decision Support System, Practice Facilitation, Small Independent Practices
|
Hypertension, Vascular Diseases, Cardiovascular Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CDS alone<br>This arm will only receive the CDS. | Other: CDS Alone<br>* The practices in the 'CDS alone' arm will receive an updated CDS for HTN management.<br>|
| Active Comparator: CDS plus practice facilitation<br>This arm will receive the CDS and practice facilitation. | Other: CDS plus practice facilitation<br>* The practices in the 'CDS plus practice facilitation' arm will receive an updated CDS for HTN management plus practice facilitation to support the adoption of the CDS.<br>|
|
Practice Facilitation to Scale up a CDS for Hypertension Management
Study Overview
=================
Brief Summary
-----------------
Hypertension (HTN) is the most prevalent modifiable risk factor for cardiovascular disease among U.S. adults. Despite a long history of established guidelines to support clinical management, only half of U.S. adults diagnosed with HTN have poorly controlled blood pressure (BP) and medication adherence to proven effective treatment remains suboptimal. Clinical decision support (CDS) has the potential to overcome barriers to delivering guideline-recommended care and improve HTN management. Practice facilitation is a well-demonstrated implementation strategy to support process changes and has the potential to facilitate CDS implementation. Our objective is to rigorously evaluate whether practice facilitation provided in concert with a HTN-focused CDS that incorporates medication adherence results is an effective strategy for scaling and implementing CDS. The investigators will update an existing CDS to incorporate alerts and tools to address medication adherence then randomize 40 small independent primary care practices in New York City to receive either practice facilitation in addition to the CDS or the CDS alone. After a twelve-month intervention period, The investigators will examine the differences in blood pressure control achieved by practices in the CDS plus practice facilitation group versus practices that received the CDS alone
Detailed Description
-----------------
Hypertension (HTN) is the most prevalent modifiable risk factor for cardiovascular disease among U.S. adults. Despite a long history of established guidelines to support clinical management, only half of U.S. adults diagnosed with HTN have poorly controlled blood pressure (BP) and medication adherence to proven effective treatment remains suboptimal. Clinical decision support (CDS) has the potential to overcome barriers to delivering guideline-recommended care and improve HTN management. However, optimal strategies for scaling CDS have not been well established, particularly in small independent primary care practices which often lack the resources to effectively change practice routines in order to effectively utilize CDS. Further, CDS is used in relatively few components of the medication management process, despite indications that CDS alerts are likely to impact patient care. Practice facilitation is a well-demonstrated implementation strategy to support process changes and has the potential to facilitate CDS implementation. Our objective is to rigorously evaluate whether practice facilitation provided in concert with a HTN-focused CDS that incorporates medication adherence results is an effective strategy for scaling and implementing CDS. The investigators will initially update and incorporate an evidence-based hypertension-focused CDS shown to be effective in Federally Qualified Health Centers (FQHCs) into an existing commercial electronic health record (EHR) system used by a large network of independent primary care practices. This CDS will employ several features shown to be effective in the FQHCs, including passive alerts, order sets, documentation templates, standardized medication adherence questionnaires, and clinical reminders. Additionally, the CDS will incorporate a new feature, a medication adherence alert based on prescription claims data. The investigators will then randomize 40 small independent primary care practices in New York City to receive either practice facilitation in addition to the CDS or the CDS alone. The PF intervention will include an initial training in the CDS and review of current guidelines along with follow-up in-person and remote meetings for coaching and supporting integration into the workflow. After a twelve-month intervention period, The investigators will examine the differences in blood pressure control achieved by practices in the CDS plus practice facilitation group versus practices that received the CDS alone. The investigators will also assess the implementation process for scaling the CDS using the RE-AIM framework. The results of this study will inform future efforts to implement and scale CDS into small primary care practices, where much of care delivery occurs in the U.S.
Official Title
-----------------
Assessing the Use of Practice Facilitation to Optimize Scale up of CDS for Hypertension
Conditions
-----------------
Hypertension
Intervention / Treatment
-----------------
* Other: CDS Alone
* Other: CDS plus practice facilitation
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18-85 years old an outpatient clinic visit with an HTN diagnosis based on the ICD-10 code in the prior 12 months must have received care at the clinic for at least 12 months Exclusion Criteria: not pregnant not have end-stage kidney disease as defined by an ICD-10 code for dialysis or transplantation
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CDS alone<br>This arm will only receive the CDS. | Other: CDS Alone<br>* The practices in the 'CDS alone' arm will receive an updated CDS for HTN management.<br>|
| Active Comparator: CDS plus practice facilitation<br>This arm will receive the CDS and practice facilitation. | Other: CDS plus practice facilitation<br>* The practices in the 'CDS plus practice facilitation' arm will receive an updated CDS for HTN management plus practice facilitation to support the adoption of the CDS.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients who had a diagnosis of hypertension (HTN) and whose blood pressure (BP) was adequately controlled using BP documented in the electronic health record | The primary outcome will be a measure of clinical effectiveness, or the percentage of patients who have achieved BP control, defined as BP <140/90 mmHg in the mean of the last two EHR-recorded measurements during each of the pre-intervention and post-intervention study periods. | 12-months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in average systolic and diastolic blood pressure (mmHg) of patients who had a diagnosis of hypertension (HTN) using BP documented in the electronic health record | A secondary measure will be the average change in systolic and diastolic BP (mmHg) of patients who had a diagnosis of HTN between the pre- and post-intervention period. | 12-months |
| Percentage of patients who had a diagnosis of hypertension (HTN) and a documented blood pressure (BP)-lowering medication and whose calculated medication adherence rate is considered adherent using pharmacy claims data | A secondary outcome will be percentage of patients who had a diagnosis of HTN and a documented BP-lowering medication and whose calculated medication adherence rate is considered adherent pre- and post-intervention period. Adherence is measured as proportion of days covered (PDC) where a PDC >80% is considered adherent. PDC is calculated using prescription fill data from pharmacy claims. | 12-months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Clinical Decision Support System, Practice Facilitation, Small Independent Practices
|
NCT02731885
|
Food Effect on Pharmacokinetic Parameters of ABX464
|
The goal of this study is to determine the impact of the food on the absorption of the ABX464.
|
This is a phase I, single-center, open-label, two-treatment, food-effect, randomized study in 40 healthy Caucasian male subjects in order to determine the impact of the food on the absorption of the ABX464.~The two different treatments are the followings:~Treatment A = 50mg of ABX464 (two 25mg capsules) /Fasted~Treatment B = 50mg of ABX464 (two 25mg capsules) / Fed~This study consists of two groups:~Group 1 - single dose assessments, two-period, two-treatment, cross-over: 20 subjects will receive a single dose of 50mg of ABX464 in fed and fasted condition, separated by a wash-out period of at least 45 days.~Group 2 - multiple dose assessments: 20 subjects will receive 50mg of ABX464 every 3 days during 10 days in fasted or fed condition.
|
An Open, Randomized Study, to Investigate the Potential Food Effect on Pharmacokinetic Parameters of ABX464 Administered Orally to Healthy Male Subjects
|
Healthy Volunteers
|
* Drug: ABX464 Single dose
* Drug: ABX464 Repeated dose
|
Inclusion Criteria:~Healthy Caucasian male subjects, 18-55 years of age~Body Mass Index (BMI) of 17-28 kg/m².~Certified as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination)~Normal vital signs after 10 minutes resting in supine position:~90 mmHg < systolic blood pressure < 140 mmHg, 50 mmHg < diastolic blood pressure < 90 mmHg, 40 bpm < heart rate < 100 bpm.~Normal automatic 12-lead ECG (incomplete right bundle branch block can be accepted) or judged as non clinically significant.~Clinical laboratory tests (hematology, blood chemistry, and urinalysis) must be within normal limits or clinically acceptable to Investigator and Sponsor.~Subjects must be willing to give written informed consent prior to study enrollment and be able to adhere to restrictions and examination schedules.~Exclusion Criteria:~Individuals with a history of any significant medical disorder which requires a physician's care (cardiovascular, pulmonary, gastro-intestinal, hepatic, renal, metabolic, hematological, neurologic, psychiatric, systemic, or infectious disease; any acute infectious disease or signs of acute illness)~Frequent headaches and / or migraine, recurrent nausea and / or vomiting (more than twice a month).~Presence or history of drug allergy, or allergic disease diagnosed and treated by a physician.~Individuals who have a history of any clinically significant local or systemic infectious disease within 4 weeks prior to drug administration.~Any individual who does not comply with the requirement that he should not have used any drugs other than paracetamol for at least 2 weeks prior to the study nor alcohol within 48 hours prior to drug administration.~Individuals who are positive for hepatitis B virus, hepatitis C virus or HIV.~History or presence of drug or alcohol abuse (positive urine drug screen, positive alcohol breath test).~Smoking more than 5 cigarettes or equivalent / day, unable to stop smoking during the study.~Excessive consumption of beverages with xanthine bases (> 4 cups or glasses / day).~Subject who will likely be unable to eat entirely the standard high fat breakfast within the allocated time.~Individuals who have donated blood within the preceding 3 months.~Individuals who refuse to use an effective method of contraception from the beginning of the study and until 3 months after dosing.~Individuals with forfeiture of freedom by an administrative or legal obligation or under guardianship
|
18 Years
|
55 Years
|
Male
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration versus time curve (AUC) of single oral dose of 50mg of ABX464 in fed or fasted condition. | | 45 days |
| Peak Plasma Concentration (Cmax) of single oral dose of 50mg of ABX464 in fed or fasted condition. | | 45 days |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration versus time curve (AUC) of repeated doses of 50 mg of ABX464 in fed or fasted conditions | | 10 days |
| Peak Plasma Concentration (Cmax) of repeated doses of 50 mg of ABX464 in fed or fasted conditions | | 10 days |
| Number of Subjects with treatment-related adverse events as assessed by CTCAE v4.0 | | Up to 45 days |
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fasted Conditions<br>50mg of ABX464 (two 25mg capsules) /Fasted | Drug: ABX464 Single dose<br>* Two-periods, subjects received a single dose of 50mg of ABX464 in fed and fasted condition, separated by a wash-out period of at least 45 days.<br>Drug: ABX464 Repeated dose<br>* Subjects received 50mg of ABX464 every 3 days during 10 days in fasted or fed condition.<br>|
| Experimental: Fed Conditions<br>50mg of ABX464 (two 25mg capsules) /Fed | Drug: ABX464 Single dose<br>* Two-periods, subjects received a single dose of 50mg of ABX464 in fed and fasted condition, separated by a wash-out period of at least 45 days.<br>Drug: ABX464 Repeated dose<br>* Subjects received 50mg of ABX464 every 3 days during 10 days in fasted or fed condition.<br>|
|
Food Effect on Pharmacokinetic Parameters of ABX464
Study Overview
=================
Brief Summary
-----------------
The goal of this study is to determine the impact of the food on the absorption of the ABX464.
Detailed Description
-----------------
This is a phase I, single-center, open-label, two-treatment, food-effect, randomized study in 40 healthy Caucasian male subjects in order to determine the impact of the food on the absorption of the ABX464. The two different treatments are the followings: Treatment A = 50mg of ABX464 (two 25mg capsules) /Fasted Treatment B = 50mg of ABX464 (two 25mg capsules) / Fed This study consists of two groups: Group 1 - single dose assessments, two-period, two-treatment, cross-over: 20 subjects will receive a single dose of 50mg of ABX464 in fed and fasted condition, separated by a wash-out period of at least 45 days. Group 2 - multiple dose assessments: 20 subjects will receive 50mg of ABX464 every 3 days during 10 days in fasted or fed condition.
Official Title
-----------------
An Open, Randomized Study, to Investigate the Potential Food Effect on Pharmacokinetic Parameters of ABX464 Administered Orally to Healthy Male Subjects
Conditions
-----------------
Healthy Volunteers
Intervention / Treatment
-----------------
* Drug: ABX464 Single dose
* Drug: ABX464 Repeated dose
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy Caucasian male subjects, 18-55 years of age Body Mass Index (BMI) of 17-28 kg/m². Certified as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination) Normal vital signs after 10 minutes resting in supine position: 90 mmHg < systolic blood pressure < 140 mmHg, 50 mmHg < diastolic blood pressure < 90 mmHg, 40 bpm < heart rate < 100 bpm. Normal automatic 12-lead ECG (incomplete right bundle branch block can be accepted) or judged as non clinically significant. Clinical laboratory tests (hematology, blood chemistry, and urinalysis) must be within normal limits or clinically acceptable to Investigator and Sponsor. Subjects must be willing to give written informed consent prior to study enrollment and be able to adhere to restrictions and examination schedules. Exclusion Criteria: Individuals with a history of any significant medical disorder which requires a physician's care (cardiovascular, pulmonary, gastro-intestinal, hepatic, renal, metabolic, hematological, neurologic, psychiatric, systemic, or infectious disease; any acute infectious disease or signs of acute illness) Frequent headaches and / or migraine, recurrent nausea and / or vomiting (more than twice a month). Presence or history of drug allergy, or allergic disease diagnosed and treated by a physician. Individuals who have a history of any clinically significant local or systemic infectious disease within 4 weeks prior to drug administration. Any individual who does not comply with the requirement that he should not have used any drugs other than paracetamol for at least 2 weeks prior to the study nor alcohol within 48 hours prior to drug administration. Individuals who are positive for hepatitis B virus, hepatitis C virus or HIV. History or presence of drug or alcohol abuse (positive urine drug screen, positive alcohol breath test). Smoking more than 5 cigarettes or equivalent / day, unable to stop smoking during the study. Excessive consumption of beverages with xanthine bases (> 4 cups or glasses / day). Subject who will likely be unable to eat entirely the standard high fat breakfast within the allocated time. Individuals who have donated blood within the preceding 3 months. Individuals who refuse to use an effective method of contraception from the beginning of the study and until 3 months after dosing. Individuals with forfeiture of freedom by an administrative or legal obligation or under guardianship
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years
Sexes Eligible for Study
-----------------
Male
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fasted Conditions<br>50mg of ABX464 (two 25mg capsules) /Fasted | Drug: ABX464 Single dose<br>* Two-periods, subjects received a single dose of 50mg of ABX464 in fed and fasted condition, separated by a wash-out period of at least 45 days.<br>Drug: ABX464 Repeated dose<br>* Subjects received 50mg of ABX464 every 3 days during 10 days in fasted or fed condition.<br>|
| Experimental: Fed Conditions<br>50mg of ABX464 (two 25mg capsules) /Fed | Drug: ABX464 Single dose<br>* Two-periods, subjects received a single dose of 50mg of ABX464 in fed and fasted condition, separated by a wash-out period of at least 45 days.<br>Drug: ABX464 Repeated dose<br>* Subjects received 50mg of ABX464 every 3 days during 10 days in fasted or fed condition.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration versus time curve (AUC) of single oral dose of 50mg of ABX464 in fed or fasted condition. | | 45 days |
| Peak Plasma Concentration (Cmax) of single oral dose of 50mg of ABX464 in fed or fasted condition. | | 45 days |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration versus time curve (AUC) of repeated doses of 50 mg of ABX464 in fed or fasted conditions | | 10 days |
| Peak Plasma Concentration (Cmax) of repeated doses of 50 mg of ABX464 in fed or fasted conditions | | 10 days |
| Number of Subjects with treatment-related adverse events as assessed by CTCAE v4.0 | | Up to 45 days |
|
||
NCT05138926
|
Effect of Spinal Manipulation on Electromyography of the Masseter Muscle
|
Research Problem: To know the immediate effects of high speed and low amplitude cervical manipulation on the electromyographic activity of the masseter muscles of physiotherapy students at the University of the Americas Course objective: To compare the immediate effects of high-speed, low-amplitude cervical manipulation on the electromyographic activity of the masseter muscles versus a placebo intervention in kinesiology students at the University of the Americas.~Specific objectives: To describe the changes in the electromyographic activity of the masseter muscles of the high-speed cervical manipulation group in students of the physiotherapy school of the University of the Americas of the Santiago Centro campus.~To describe the changes in the electromyographic activity of the masseter muscles of the placebo group in students of the physiotherapy school of the University of the Americas of the Santiago Centro campus.~Methodology: Single-blind, randomized clinical trial. Expected results: Significant differences are expected between the intervention group and the control group. This is reflected in a decrease in electromyographic activity in the masseter muscles after high-speed cervical manipulation.
|
Immediate Effect of High Speed and Low Amplitude Cervical Manipulation on the Electromyographic Activity of the Masseter Muscle, in a Physiotherapy Students at the University of the Americas. a Clinical Trial, Single Blind
|
Bruxism, Muscle Disorder
|
* Other: Cervical Manipulation
* Other: Sham Cervical Manipulation
|
Inclusion Criteria:~Male and female physiotherapy students over 18 years of age who regularly attend face-to-face classes who have a mobility pass and a health declaration.~Students who read and sign the informed consent.~Exclusion Criteria:~Orthognathic surgery.~Recent head and neck injury or fracture (equal to or less than 3 months)~Dental or medical diagnosis of mandibular disorder or manifest facial pain.~Contraindication (red flag) to perform high speed and low amplitude cervical manipulation (bone cancer, osteoporosis, vertebral artery injury, etc.)
|
18 Years
| null |
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Electromyography of the masseter muscle before intervention | surface electromyography of the masseter muscle, measured in millivolts (mV) | baseline |
| Electromyography of the masseter muscle after the intervention | surface electromyography of the masseter muscle, measured in millivolts (mV) | 5 minute after intervention |
|
Muscular Diseases, Bruxism, Tooth Diseases, Stomatognathic Diseases, Musculoskeletal Diseases, Neuromuscular Diseases, Nervous System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cervical manipulation group<br>high speed, low amplitude cervical manipulation | Other: Cervical Manipulation<br>* high speed, low amplitude cervical manipulation<br>|
| Sham Comparator: Control group<br>placebo mobilization without manipulation | Other: Sham Cervical Manipulation<br>* Cervical mobilization without performing spinal manipulation<br>|
|
Effect of Spinal Manipulation on Electromyography of the Masseter Muscle
Study Overview
=================
Brief Summary
-----------------
Research Problem: To know the immediate effects of high speed and low amplitude cervical manipulation on the electromyographic activity of the masseter muscles of physiotherapy students at the University of the Americas Course objective: To compare the immediate effects of high-speed, low-amplitude cervical manipulation on the electromyographic activity of the masseter muscles versus a placebo intervention in kinesiology students at the University of the Americas. Specific objectives: To describe the changes in the electromyographic activity of the masseter muscles of the high-speed cervical manipulation group in students of the physiotherapy school of the University of the Americas of the Santiago Centro campus. To describe the changes in the electromyographic activity of the masseter muscles of the placebo group in students of the physiotherapy school of the University of the Americas of the Santiago Centro campus. Methodology: Single-blind, randomized clinical trial. Expected results: Significant differences are expected between the intervention group and the control group. This is reflected in a decrease in electromyographic activity in the masseter muscles after high-speed cervical manipulation.
Official Title
-----------------
Immediate Effect of High Speed and Low Amplitude Cervical Manipulation on the Electromyographic Activity of the Masseter Muscle, in a Physiotherapy Students at the University of the Americas. a Clinical Trial, Single Blind
Conditions
-----------------
Bruxism, Muscle Disorder
Intervention / Treatment
-----------------
* Other: Cervical Manipulation
* Other: Sham Cervical Manipulation
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male and female physiotherapy students over 18 years of age who regularly attend face-to-face classes who have a mobility pass and a health declaration. Students who read and sign the informed consent. Exclusion Criteria: Orthognathic surgery. Recent head and neck injury or fracture (equal to or less than 3 months) Dental or medical diagnosis of mandibular disorder or manifest facial pain. Contraindication (red flag) to perform high speed and low amplitude cervical manipulation (bone cancer, osteoporosis, vertebral artery injury, etc.)
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cervical manipulation group<br>high speed, low amplitude cervical manipulation | Other: Cervical Manipulation<br>* high speed, low amplitude cervical manipulation<br>|
| Sham Comparator: Control group<br>placebo mobilization without manipulation | Other: Sham Cervical Manipulation<br>* Cervical mobilization without performing spinal manipulation<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Electromyography of the masseter muscle before intervention | surface electromyography of the masseter muscle, measured in millivolts (mV) | baseline |
| Electromyography of the masseter muscle after the intervention | surface electromyography of the masseter muscle, measured in millivolts (mV) | 5 minute after intervention |
|
|||
NCT04644744
|
Hypothermic Oxygenated (HOPE) Versus Normothermic Machine Perfusion (NMP) in Human Liver Transplantation
|
The common practice of conventional cold storage (CCS) organ preservation has changed little since the initial introduction of the original University of Wisconsin (UW) organ preservation solution in the late 1980s. CCS relies on hypothermia to decelerate metabolism and reduce oxygen demand in order to prolong the time of ischemia without rapid functional graft impairment, therefore merely delaying graft damage. While CCS only prolongs storage time and limits the damage sustained during the period of cold ischemia, ex-vivo machine perfusion (MP) appears to be capable of reversing some of these effects. Currently, two main paradigms prevail in the clinical approach to liver allograft MP: hypothermic oxygenated MP (HOPE) may be seen as a dynamic alternative of the traditional organ preservation based on hypothermia-induced deceleration of metabolism, which aims to combine the positive effects of hypothermia observed in classical cold storage (e.g. technical simplicity, relative safety, decreased metabolism) with the positive effects of dynamic preservation (e.g. controlled sheer stress mediated gene activation, removal of metabolites, transport of oxygen and ATP recharging). Normothermic perfusion (NMP) aims at re-equilibration of cellular metabolism by preserving the organ at physiological temperatures whilst ensuring sufficient oxygen and nutrient supply. In both approaches, the perpetual circulation and moderate shear-stress sustain endothelial functionality. While past and current clinical trials were designed to compare different MP approaches with CCS as the clinical standard, a direct comparison between different end-ischemic MP techniques (HOPE versus NMP) is still lacking. The purpose of this study is to test the effects of end-ischemic NMP versus end-ischemic HOPE technique in a multicentre prospective randomized controlled clinical trial (RCT) on ECD liver grafts in DBD liver-transplantation (HOPE-NMP). Two-hundred-thirteen (n = 213) human whole organ liver grafts will be submitted to either 4-24 hours of NMP (n = 85) or 2-3 hours of HOPE (n = 85) directly before implantation and going to be compared to a control-group of patients (n = 43) transplanted with static cold storage preserved ECD-allografts. Primary (surgical complications as assessed by the comprehensive complication index [CCI]) and secondary (among others laboratory values, graft- and patient survival, hospital costs, hospital stay) endpoints are going to be analysed.)
|
Liver transplantation has evolved as the mainstay of treatment for end-stage liver disease. While the demand for organ transplantation has increased over time, Germany's organ donation rate is low compared to other countries. The main indications for listing are 'fibrosis and cirrhosis' (27%) followed by 'alcoholic liver disease' (23%) and 'hepatic malignancies' (17%).~With the advent of emerging waiting list mortality, several strategies for donor pool expansion are being pursued; these include the use of living donors, splitting of cadaveric livers for two recipients, and the use of extended criteria donor (ECD) allografts for OLT. These ECD-allografts, however, exhibit poor tolerance to ischemia-reperfusion (I/R) injury, an important cause of liver damage. As such, I/R-injury is the underlying cause of graft dysfunction in ECD-allografts and negatively affects the process of liver regeneration in surgical conditions including hepatic resections and OLT.~Machine perfusion with oxygenated blood was already implemented in the first series of 11 successful human OLTs in the 1960s. While the logistical simplicity and reliable performance of CCS led to its quick adoption as the standard solid organ preservation technique, the increased utilization of high-risk organs has unveiled the limitations of CCS, furthering the debate on the impact of different MP techniques. Today, perfusion conditions vary broadly, especially in preclinical research. Parameters under discussion include different temperatures, perfusate composition, the application of perfusion flow (continuous or pulsatile), the timing and duration of the perfusion, starting either at the donor site or applied only end-ischemic in the recipient centre. Two main principles have been translated into clinical practice today: hypothermic oxygenated perfusion (HOPE) and normothermic MP (NMP). The latter differs significantly from HOPE because the allograft is perfused with oxygenated red blood cells or oxygen carriers at physiological temperatures with the aim to reduce the ischemic graft injury by minimizing the duration of cold preservation and perfectly mimicking physiological conditions. A recently completed randomized controlled trial (RCT) by Nasralla et al. proved the feasibility of NMP for OLT and demonstrated a significant reduction in peak AST and subsequent early allograft dysfunction (EAD), however without a significant difference in graft and patient survival. Most recently, a development of the NMP technique that allowed a 7-day preservation of human livers with a sustained metabolic function and an intact liver structure was recently reported by Eshmuminov et al. Based on the sustained full hepatic metabolism during NMP, several groups are currently exploring the possibility of normothermic viability testing. The cellular mechanisms of organ protection by NMP do not center around IRI mitigation and reconditioning, but IRI prevention, and are altogether different from cold perfusion techniques. While normothermic machine perfusion is most effective when applied during the entire period of organ preservation, the end-ischemic application of this technique in the recipient hospital is becoming more popular.~There are two main hypotheses on the underlying mechanisms of HOPE induced organ protection; (I.) modulation of cellular metabolism (energy household, mitochondrial respiration), and (II.) stimulation of the sinusoidal endothelial layer. Although, tissue oxygen consumption is markedly decreased at 4-10 Celsius, it is not completely suspended. The shift of mitochondrial metabolism to anaerobic pathways leads to expressed mitochondrial metabolite accumulation during ischemia and subsequently to extreme radical oxygen species (ROS) generation through rapid re-oxidization by the early reperfusion respiratory burst. The delivery of oxygen during cold preservation can effectively upload cellular energy household via various mitochondrial pathways. Pre-implantation resuscitation of organs with machine perfusion and oxygen can increase tissue ATP levels and decrease the post-ischemic production of ROS and danger-associated molecular patterns (DAMPs), this subsequently leads to a mitigated immune response. This organ conditioning effect is attributed to a controlled re-oxygenation inducing moderate ROS release just before reperfusion. These low levels of ROS are not only responsible for the induction of antioxidant enzymes (heme-oxygenase, gluthathione-synthase, superoxide-dismutase), but are also responsible for the stimulation of protein mediators of innate pro-survival mechanisms. A further mechanism behind the protective effects of dynamic preservation approaches is the presence of shear stress and as such active perfusion during the preservation phase may induce specific shear stress-sensitive genes some of which include Kruppel-like factor 2 or endothelial nitric oxide synthase. Currently, three multicenter RCTs have completed their patient recruitment and clinical results are expected for the year 2021. The Zurich group initiated a multicentric RCT to assess the impact of HOPE on any DBD liver graft including retransplantations and marginal livers and is powered to assess major complications (Clavien grade ≥III) (NCT01317342). The Groningen team explores the dual HOPE (d-HOPE) technique in DCD grafts (NCT02584283) and our own group initiated a multicentric RCT on HOPE in ECD-DBD liver transplantation in 2017 (NCT03124641).~Viability assessment during MP can guide the clinical decision whether to accept a liver for transplantation and is therefore an important emerging tool in ECD OLT. The possibility of a reliable viability assessment is advocated as a considerable advantage of normothermic perfusion techniques. By sustaining full metabolism, NMP allows to analyse several makers of liver function and injury, including biliary parameters (e.g. bile flow, bile glucose, bicarbonate and pH), perfusate pH and base excess, portal venous- and hepatic artery flow and perfusate hepatocellular enzymes. Despite the reduced metabolic activity during cold storage and hypothermic liver perfusion, there is increasing evidence that a prediction of future graft performance after transplantation may be possible during HOPE, as well. Analysis of the cold perfusate during HOPE provides a unique opportunity to identity potential biomarkers which are associated with various post-OLT outcomes. A recent study involving 31 human ECD-DBD grafts initially rejected for transplantation, found that cold perfusion not only ameliorates reperfusion injury but also allows for graft viability assessment. Thus, the 2-hour perfusate AST and lactate dehydrogenase (LDH) correlated significantly with the peak AST after implantation. In two grafts with a significant postreperfusion transaminase release, a high portal perfusion pressure was noted.~The Zurich group has recently presented a new mitochondrial marker to assess viability of entire liver grafts during HOPE. Real-time fluorometric analysis of mitochondrial flavin mononucleotide (FMN) in the HOPE perfusate predicted human liver function, complications and graft loss prior to transplantation. The use of this surrogate parameter could facilitate proper clinical decision making whether to accept or decline allografts in the HOPE setting. This marker is currently validated in other solid organs and also in the RCT of Guarerras working group. Importantly, the quantification of FMN is possible in real time, requiring only a spectroscope to reliably predict graft survival within the first 30-45 minutes of HOPE. The clinical value and head-to-head comparison of various allograft viability parameters in the HOPE vs. NMP setting has yet to be explored in the setting of a large multicenter RCT. With the advent of clinical MP and the context of a dire donation situation in the western world, it will be of utmost clinical importance to identify the most effective dynamic preservation technique. While past and current clinical trials in DCD and DBD liver transplantation were designed to compare different MP approaches with CCS as the clinical standard, a direct comparison between different end-ischemic MP techniques (HOPE versus NMP) is still lacking.
|
End-ischemic Hypothermic Oxygenated (HOPE) vs. Normothermic Machine Perfusion (NMP) Compared to Conventional Cold Storage in Donation After Brain Death Liver Transplantation; a Prospective Multicentre Randomized Controlled Trial (HOPE-NMP)
|
Hepatocellular Injury, Liver Transplant Disorder
|
* Device: Hypothermic oxygenated perfusion (HOPE)
* Device: Normothermic machine perfusion (NMP)
|
Inclusion Criteria:~Signed informed consent~Patients 18 years or older~Patients suffering from end stage-liver disease and/or malignant liver tumours~Listed for OLT~Receiving ECD-allografts~Exclusion Criteria:~Recipients of split or living donor liver transplants~Previous liver transplantation~Combined transplantations (liver-kidney, liver-lung, etc.)~Participation in other liver related trials~The subject received an investigational drug within 30 days prior to inclusion~The subject is unwilling or unable to follow the procedures outlined in the protocol~The subject is mentally or legally incapacitated~Patient is not able to understand the procedures due to language barriers~Family members of the investigators or employees of the participating departments
|
18 Years
|
75 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized controlled trial
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative complications | Comprehensive Complication Index (CCI) (assessed after the first 90-days postoperatively) | After the first 90-days postoperatively |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak alanine aminotransferase (ALT) | Peak serum alanine aminotransferase-ALT | During the first week postoperatively |
| Peak aspartate aminotransferase (AST) | Peak serum aspartate aminotransferase-AST | During the first week postoperatively |
| Early allograft dysfunction (EAD) | Olthoff criteria (bilirubin 10mg/dL on day 7, international normalized ratio 1.6 on day 7, and alanine or aspartate aminotransferases >2000 IU/L) | During the first week postoperatively |
| Primary non-function (PNF) | Graft with poor function requiring re-transplantation or leading to death within 7 days after the primary procedure without any identifiable cause of graft failure | During the first week postoperatively |
| Biliary complications | as assessed by MRI / MRCP | at 6 months postoperatively |
| Organ utilization rate | Rate of donor-allograft offers that result in liver transplantation | During the first week postoperatively |
| Total organ preservation time | Organ logistics | Before preservation (HOPE or NPM or CCS), after liver implantation (0-3 hours) |
| Duration and costs of initial intensive care unit (ICU) stay | Length of initial Intensive care unit (ICU) stay is determined in days of admission following liver transplantation. | Subjects will be followed for 6 months postoperatively |
| Duration of hospital stay | Length of hospital stay is determined in days of hospital admission after discharge and up to six months after liver transplantation | Subjects will be followed for 6 months postoperatively |
| Costs of hospital stay | Costs of hospital stay is determined in days of hospital admission after discharge and up to six months after liver transplantation | Subjects will be followed for 6 months postoperatively |
| Postoperative complications | According to the Comprehensive complication index (CCI) | Subjects will be followed for one year postoperatively |
| Postoperative major complications | According to the Clavien-Dindo complication score | Subjects will be followed for one year postoperatively |
| One-year recipient- and graft survival | One year patient and graft survival | Subjects will be followed for one year postoperatively |
|
NMP, ex-vivo machine Perfusion, Hypothermic oxygenated machine perfusion, Normothermic machine perfusion, Orthotopic liver transplantation, Extended criteria donation, Donation after brain death, HOPE
|
Hypothermia, Body Temperature Changes
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hypothermic oxygenated perfusion (HOPE)<br>Application of end-ischemic Hypothermic machine perfusion (HOPE) for a minimum of 2 hours (until hepatectomy) | Device: Hypothermic oxygenated perfusion (HOPE)<br>* HOPE for 1 hour via the portal vein in a recirculating and pressure controlled system (2-3 mm Hg), 0.1 ml/g liver/min, perfusion volume 3-4 L, Belzer (UW) machine perfusion solution, perfusate temperature 10 °C, perfusate oxygenation pO2 of 60-80 kPa<br>* Other names: Hypothermic machine perfusion (HMP);|
| Experimental: Normothermic machine perfusion (NMP)<br>Application of end-ischemic normothermic machine perfusion (NMP) for a minimum of 4 hours (up to 24 hours) | Device: Normothermic machine perfusion (NMP)<br>* End-ischemic NMP will be continued throughout the recipient hepatectomy and until the transplanting team is ready to implant the liver. The minimum protocol-stipulated NMP duration is 4 hours, the time needed for ATP repletion in animal studies. Total NMP preservation time will be according to the official recommendations of the manufacturer (4-24 hours) and at the discretion of the local transplant centre. The liver allograft will be disconnected from the OrganOx metra® device immediately prior to transplantation and flushed with three litres of HTK via the hepatic artery and the portal vein.<br>|
| Active Comparator: Conventional cold storage (CCS)<br>Conventional cold storage | Device: Hypothermic oxygenated perfusion (HOPE)<br>* HOPE for 1 hour via the portal vein in a recirculating and pressure controlled system (2-3 mm Hg), 0.1 ml/g liver/min, perfusion volume 3-4 L, Belzer (UW) machine perfusion solution, perfusate temperature 10 °C, perfusate oxygenation pO2 of 60-80 kPa<br>* Other names: Hypothermic machine perfusion (HMP);Device: Normothermic machine perfusion (NMP)<br>* End-ischemic NMP will be continued throughout the recipient hepatectomy and until the transplanting team is ready to implant the liver. The minimum protocol-stipulated NMP duration is 4 hours, the time needed for ATP repletion in animal studies. Total NMP preservation time will be according to the official recommendations of the manufacturer (4-24 hours) and at the discretion of the local transplant centre. The liver allograft will be disconnected from the OrganOx metra® device immediately prior to transplantation and flushed with three litres of HTK via the hepatic artery and the portal vein.<br>|
|
Hypothermic Oxygenated (HOPE) Versus Normothermic Machine Perfusion (NMP) in Human Liver Transplantation
Study Overview
=================
Brief Summary
-----------------
The common practice of conventional cold storage (CCS) organ preservation has changed little since the initial introduction of the original University of Wisconsin (UW) organ preservation solution in the late 1980s. CCS relies on hypothermia to decelerate metabolism and reduce oxygen demand in order to prolong the time of ischemia without rapid functional graft impairment, therefore merely delaying graft damage. While CCS only prolongs storage time and limits the damage sustained during the period of cold ischemia, ex-vivo machine perfusion (MP) appears to be capable of reversing some of these effects. Currently, two main paradigms prevail in the clinical approach to liver allograft MP: hypothermic oxygenated MP (HOPE) may be seen as a dynamic alternative of the traditional organ preservation based on hypothermia-induced deceleration of metabolism, which aims to combine the positive effects of hypothermia observed in classical cold storage (e.g. technical simplicity, relative safety, decreased metabolism) with the positive effects of dynamic preservation (e.g. controlled sheer stress mediated gene activation, removal of metabolites, transport of oxygen and ATP recharging). Normothermic perfusion (NMP) aims at re-equilibration of cellular metabolism by preserving the organ at physiological temperatures whilst ensuring sufficient oxygen and nutrient supply. In both approaches, the perpetual circulation and moderate shear-stress sustain endothelial functionality. While past and current clinical trials were designed to compare different MP approaches with CCS as the clinical standard, a direct comparison between different end-ischemic MP techniques (HOPE versus NMP) is still lacking. The purpose of this study is to test the effects of end-ischemic NMP versus end-ischemic HOPE technique in a multicentre prospective randomized controlled clinical trial (RCT) on ECD liver grafts in DBD liver-transplantation (HOPE-NMP). Two-hundred-thirteen (n = 213) human whole organ liver grafts will be submitted to either 4-24 hours of NMP (n = 85) or 2-3 hours of HOPE (n = 85) directly before implantation and going to be compared to a control-group of patients (n = 43) transplanted with static cold storage preserved ECD-allografts. Primary (surgical complications as assessed by the comprehensive complication index [CCI]) and secondary (among others laboratory values, graft- and patient survival, hospital costs, hospital stay) endpoints are going to be analysed.)
Detailed Description
-----------------
Liver transplantation has evolved as the mainstay of treatment for end-stage liver disease. While the demand for organ transplantation has increased over time, Germany's organ donation rate is low compared to other countries. The main indications for listing are 'fibrosis and cirrhosis' (27%) followed by 'alcoholic liver disease' (23%) and 'hepatic malignancies' (17%). With the advent of emerging waiting list mortality, several strategies for donor pool expansion are being pursued; these include the use of living donors, splitting of cadaveric livers for two recipients, and the use of extended criteria donor (ECD) allografts for OLT. These ECD-allografts, however, exhibit poor tolerance to ischemia-reperfusion (I/R) injury, an important cause of liver damage. As such, I/R-injury is the underlying cause of graft dysfunction in ECD-allografts and negatively affects the process of liver regeneration in surgical conditions including hepatic resections and OLT. Machine perfusion with oxygenated blood was already implemented in the first series of 11 successful human OLTs in the 1960s. While the logistical simplicity and reliable performance of CCS led to its quick adoption as the standard solid organ preservation technique, the increased utilization of high-risk organs has unveiled the limitations of CCS, furthering the debate on the impact of different MP techniques. Today, perfusion conditions vary broadly, especially in preclinical research. Parameters under discussion include different temperatures, perfusate composition, the application of perfusion flow (continuous or pulsatile), the timing and duration of the perfusion, starting either at the donor site or applied only end-ischemic in the recipient centre. Two main principles have been translated into clinical practice today: hypothermic oxygenated perfusion (HOPE) and normothermic MP (NMP). The latter differs significantly from HOPE because the allograft is perfused with oxygenated red blood cells or oxygen carriers at physiological temperatures with the aim to reduce the ischemic graft injury by minimizing the duration of cold preservation and perfectly mimicking physiological conditions. A recently completed randomized controlled trial (RCT) by Nasralla et al. proved the feasibility of NMP for OLT and demonstrated a significant reduction in peak AST and subsequent early allograft dysfunction (EAD), however without a significant difference in graft and patient survival. Most recently, a development of the NMP technique that allowed a 7-day preservation of human livers with a sustained metabolic function and an intact liver structure was recently reported by Eshmuminov et al. Based on the sustained full hepatic metabolism during NMP, several groups are currently exploring the possibility of normothermic viability testing. The cellular mechanisms of organ protection by NMP do not center around IRI mitigation and reconditioning, but IRI prevention, and are altogether different from cold perfusion techniques. While normothermic machine perfusion is most effective when applied during the entire period of organ preservation, the end-ischemic application of this technique in the recipient hospital is becoming more popular. There are two main hypotheses on the underlying mechanisms of HOPE induced organ protection; (I.) modulation of cellular metabolism (energy household, mitochondrial respiration), and (II.) stimulation of the sinusoidal endothelial layer. Although, tissue oxygen consumption is markedly decreased at 4-10 Celsius, it is not completely suspended. The shift of mitochondrial metabolism to anaerobic pathways leads to expressed mitochondrial metabolite accumulation during ischemia and subsequently to extreme radical oxygen species (ROS) generation through rapid re-oxidization by the early reperfusion respiratory burst. The delivery of oxygen during cold preservation can effectively upload cellular energy household via various mitochondrial pathways. Pre-implantation resuscitation of organs with machine perfusion and oxygen can increase tissue ATP levels and decrease the post-ischemic production of ROS and danger-associated molecular patterns (DAMPs), this subsequently leads to a mitigated immune response. This organ conditioning effect is attributed to a controlled re-oxygenation inducing moderate ROS release just before reperfusion. These low levels of ROS are not only responsible for the induction of antioxidant enzymes (heme-oxygenase, gluthathione-synthase, superoxide-dismutase), but are also responsible for the stimulation of protein mediators of innate pro-survival mechanisms. A further mechanism behind the protective effects of dynamic preservation approaches is the presence of shear stress and as such active perfusion during the preservation phase may induce specific shear stress-sensitive genes some of which include Kruppel-like factor 2 or endothelial nitric oxide synthase. Currently, three multicenter RCTs have completed their patient recruitment and clinical results are expected for the year 2021. The Zurich group initiated a multicentric RCT to assess the impact of HOPE on any DBD liver graft including retransplantations and marginal livers and is powered to assess major complications (Clavien grade ≥III) (NCT01317342). The Groningen team explores the dual HOPE (d-HOPE) technique in DCD grafts (NCT02584283) and our own group initiated a multicentric RCT on HOPE in ECD-DBD liver transplantation in 2017 (NCT03124641). Viability assessment during MP can guide the clinical decision whether to accept a liver for transplantation and is therefore an important emerging tool in ECD OLT. The possibility of a reliable viability assessment is advocated as a considerable advantage of normothermic perfusion techniques. By sustaining full metabolism, NMP allows to analyse several makers of liver function and injury, including biliary parameters (e.g. bile flow, bile glucose, bicarbonate and pH), perfusate pH and base excess, portal venous- and hepatic artery flow and perfusate hepatocellular enzymes. Despite the reduced metabolic activity during cold storage and hypothermic liver perfusion, there is increasing evidence that a prediction of future graft performance after transplantation may be possible during HOPE, as well. Analysis of the cold perfusate during HOPE provides a unique opportunity to identity potential biomarkers which are associated with various post-OLT outcomes. A recent study involving 31 human ECD-DBD grafts initially rejected for transplantation, found that cold perfusion not only ameliorates reperfusion injury but also allows for graft viability assessment. Thus, the 2-hour perfusate AST and lactate dehydrogenase (LDH) correlated significantly with the peak AST after implantation. In two grafts with a significant postreperfusion transaminase release, a high portal perfusion pressure was noted. The Zurich group has recently presented a new mitochondrial marker to assess viability of entire liver grafts during HOPE. Real-time fluorometric analysis of mitochondrial flavin mononucleotide (FMN) in the HOPE perfusate predicted human liver function, complications and graft loss prior to transplantation. The use of this surrogate parameter could facilitate proper clinical decision making whether to accept or decline allografts in the HOPE setting. This marker is currently validated in other solid organs and also in the RCT of Guarerras working group. Importantly, the quantification of FMN is possible in real time, requiring only a spectroscope to reliably predict graft survival within the first 30-45 minutes of HOPE. The clinical value and head-to-head comparison of various allograft viability parameters in the HOPE vs. NMP setting has yet to be explored in the setting of a large multicenter RCT. With the advent of clinical MP and the context of a dire donation situation in the western world, it will be of utmost clinical importance to identify the most effective dynamic preservation technique. While past and current clinical trials in DCD and DBD liver transplantation were designed to compare different MP approaches with CCS as the clinical standard, a direct comparison between different end-ischemic MP techniques (HOPE versus NMP) is still lacking.
Official Title
-----------------
End-ischemic Hypothermic Oxygenated (HOPE) vs. Normothermic Machine Perfusion (NMP) Compared to Conventional Cold Storage in Donation After Brain Death Liver Transplantation; a Prospective Multicentre Randomized Controlled Trial (HOPE-NMP)
Conditions
-----------------
Hepatocellular Injury, Liver Transplant Disorder
Intervention / Treatment
-----------------
* Device: Hypothermic oxygenated perfusion (HOPE)
* Device: Normothermic machine perfusion (NMP)
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed informed consent Patients 18 years or older Patients suffering from end stage-liver disease and/or malignant liver tumours Listed for OLT Receiving ECD-allografts Exclusion Criteria: Recipients of split or living donor liver transplants Previous liver transplantation Combined transplantations (liver-kidney, liver-lung, etc.) Participation in other liver related trials The subject received an investigational drug within 30 days prior to inclusion The subject is unwilling or unable to follow the procedures outlined in the protocol The subject is mentally or legally incapacitated Patient is not able to understand the procedures due to language barriers Family members of the investigators or employees of the participating departments
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized controlled trial
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hypothermic oxygenated perfusion (HOPE)<br>Application of end-ischemic Hypothermic machine perfusion (HOPE) for a minimum of 2 hours (until hepatectomy) | Device: Hypothermic oxygenated perfusion (HOPE)<br>* HOPE for 1 hour via the portal vein in a recirculating and pressure controlled system (2-3 mm Hg), 0.1 ml/g liver/min, perfusion volume 3-4 L, Belzer (UW) machine perfusion solution, perfusate temperature 10 °C, perfusate oxygenation pO2 of 60-80 kPa<br>* Other names: Hypothermic machine perfusion (HMP);|
| Experimental: Normothermic machine perfusion (NMP)<br>Application of end-ischemic normothermic machine perfusion (NMP) for a minimum of 4 hours (up to 24 hours) | Device: Normothermic machine perfusion (NMP)<br>* End-ischemic NMP will be continued throughout the recipient hepatectomy and until the transplanting team is ready to implant the liver. The minimum protocol-stipulated NMP duration is 4 hours, the time needed for ATP repletion in animal studies. Total NMP preservation time will be according to the official recommendations of the manufacturer (4-24 hours) and at the discretion of the local transplant centre. The liver allograft will be disconnected from the OrganOx metra® device immediately prior to transplantation and flushed with three litres of HTK via the hepatic artery and the portal vein.<br>|
| Active Comparator: Conventional cold storage (CCS)<br>Conventional cold storage | Device: Hypothermic oxygenated perfusion (HOPE)<br>* HOPE for 1 hour via the portal vein in a recirculating and pressure controlled system (2-3 mm Hg), 0.1 ml/g liver/min, perfusion volume 3-4 L, Belzer (UW) machine perfusion solution, perfusate temperature 10 °C, perfusate oxygenation pO2 of 60-80 kPa<br>* Other names: Hypothermic machine perfusion (HMP);Device: Normothermic machine perfusion (NMP)<br>* End-ischemic NMP will be continued throughout the recipient hepatectomy and until the transplanting team is ready to implant the liver. The minimum protocol-stipulated NMP duration is 4 hours, the time needed for ATP repletion in animal studies. Total NMP preservation time will be according to the official recommendations of the manufacturer (4-24 hours) and at the discretion of the local transplant centre. The liver allograft will be disconnected from the OrganOx metra® device immediately prior to transplantation and flushed with three litres of HTK via the hepatic artery and the portal vein.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative complications | Comprehensive Complication Index (CCI) (assessed after the first 90-days postoperatively) | After the first 90-days postoperatively |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak alanine aminotransferase (ALT) | Peak serum alanine aminotransferase-ALT | During the first week postoperatively |
| Peak aspartate aminotransferase (AST) | Peak serum aspartate aminotransferase-AST | During the first week postoperatively |
| Early allograft dysfunction (EAD) | Olthoff criteria (bilirubin 10mg/dL on day 7, international normalized ratio 1.6 on day 7, and alanine or aspartate aminotransferases >2000 IU/L) | During the first week postoperatively |
| Primary non-function (PNF) | Graft with poor function requiring re-transplantation or leading to death within 7 days after the primary procedure without any identifiable cause of graft failure | During the first week postoperatively |
| Biliary complications | as assessed by MRI / MRCP | at 6 months postoperatively |
| Organ utilization rate | Rate of donor-allograft offers that result in liver transplantation | During the first week postoperatively |
| Total organ preservation time | Organ logistics | Before preservation (HOPE or NPM or CCS), after liver implantation (0-3 hours) |
| Duration and costs of initial intensive care unit (ICU) stay | Length of initial Intensive care unit (ICU) stay is determined in days of admission following liver transplantation. | Subjects will be followed for 6 months postoperatively |
| Duration of hospital stay | Length of hospital stay is determined in days of hospital admission after discharge and up to six months after liver transplantation | Subjects will be followed for 6 months postoperatively |
| Costs of hospital stay | Costs of hospital stay is determined in days of hospital admission after discharge and up to six months after liver transplantation | Subjects will be followed for 6 months postoperatively |
| Postoperative complications | According to the Comprehensive complication index (CCI) | Subjects will be followed for one year postoperatively |
| Postoperative major complications | According to the Clavien-Dindo complication score | Subjects will be followed for one year postoperatively |
| One-year recipient- and graft survival | One year patient and graft survival | Subjects will be followed for one year postoperatively |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
NMP, ex-vivo machine Perfusion, Hypothermic oxygenated machine perfusion, Normothermic machine perfusion, Orthotopic liver transplantation, Extended criteria donation, Donation after brain death, HOPE
|
NCT02147327
|
Effects of Cord Blood 25-hydroxy-vitamin D Level on Early Neonatal Morbidities
|
Cholecalciferol (vitamin D3) is a prohormone and its active form is 1,25 dihydroxycholecalciferol. This hormone has effect on both calcium, phosphorus and bone metabolism and also bone morrow, muscle, heart and immune system. For a long time, maternal low vitamin D level is a well known problem for our country and the level was reported as <10 ng/ml for 46-80% of mothers.The most prominent risk factor was determined as low socioeconomic status. Therefore, the level of 25-hydroxy-vitamin D is supposed to be in relation with several neonatal morbidities and maternal complications of pregnancy.
| null |
Neonatal Hypocalcemia, Neonatal Sepsis
|
Inclusion Criteria:~Term or preterm newborns which are hospitalized in the Neonatal Intensive Care Unit of our hospital~Exclusion Criteria:~Preterm babies born before the 24. gestational week~Babies with complex cardiac anomalies and/or dysmorphic features
| null |
30 Minutes
|
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| sepsis | | 3 months but patients will be followed until discharge |
| feeding intolerance | | 3 months but patients will be followed until discharge |
| hypocalcemia | | 3 months but patients will be followed until discharge |
| bronchopulmonary dysplasia | | 3 months but patients will be followed until discharge |
| patent ductus arteriosis | | 3 months but patients will be followed until discharge |
| retinopathy of prematurity | | 3 months but patients will be followed until discharge |
| maternal complications of pregnancy | | from the beginning of gestation until birth process |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rachitism | | 4 months but patients will be followed until discharge |
|
vitamin D, cord blood, neonatal sepsis, neonatal morbidity
|
Neonatal Sepsis, Hypocalcemia, Sepsis, Infections, Systemic Inflammatory Response Syndrome, Inflammation, Pathologic Processes, Infant, Newborn, Diseases, Calcium Metabolism Disorders, Metabolic Diseases, Water-Electrolyte Imbalance
|
Effects of Cord Blood 25-hydroxy-vitamin D Level on Early Neonatal Morbidities
Study Overview
=================
Brief Summary
-----------------
Cholecalciferol (vitamin D3) is a prohormone and its active form is 1,25 dihydroxycholecalciferol. This hormone has effect on both calcium, phosphorus and bone metabolism and also bone morrow, muscle, heart and immune system. For a long time, maternal low vitamin D level is a well known problem for our country and the level was reported as <10 ng/ml for 46-80% of mothers.The most prominent risk factor was determined as low socioeconomic status. Therefore, the level of 25-hydroxy-vitamin D is supposed to be in relation with several neonatal morbidities and maternal complications of pregnancy.
Conditions
-----------------
Neonatal Hypocalcemia, Neonatal Sepsis
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Term or preterm newborns which are hospitalized in the Neonatal Intensive Care Unit of our hospital Exclusion Criteria: Preterm babies born before the 24. gestational week Babies with complex cardiac anomalies and/or dysmorphic features
Ages Eligible for Study
-----------------
Maximum Age: 30 Minutes
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| sepsis | | 3 months but patients will be followed until discharge |
| feeding intolerance | | 3 months but patients will be followed until discharge |
| hypocalcemia | | 3 months but patients will be followed until discharge |
| bronchopulmonary dysplasia | | 3 months but patients will be followed until discharge |
| patent ductus arteriosis | | 3 months but patients will be followed until discharge |
| retinopathy of prematurity | | 3 months but patients will be followed until discharge |
| maternal complications of pregnancy | | from the beginning of gestation until birth process |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rachitism | | 4 months but patients will be followed until discharge |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
vitamin D, cord blood, neonatal sepsis, neonatal morbidity
|
||||
NCT05055453
|
MyPhonak App Junior Pediatric Usability and Benefit Investigation
|
ESolutions functions for children and young people with the myPhonak app is a prospective study to investigate whether the myPhonak app can improve speech understanding in children with hearing aids. The study is linked to randomized patient and test allocation carried out.
|
ESolutions Functions for Children and Young People With the myPhonak App
|
Hearing Loss
|
* Device: MyPhonak Junior App
|
Inclusion Criteria:~Children and adolescents between the ages of 7 and 17 years old.~With normal middle ear characteristics~With a hearing impairment in the mild to severe range~With adequate speech development~Exclusion Criteria:~Unreliability and lack of cooperation exists,~An effusion in the middle ear or local inflammation in the ear canal or middle ear with/without a running ear,~Mental limitations,~If the patient is unable to operate a smartphone,~Other objections to study participation in the opinion of the study director exist.
|
7 Years
|
17 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in OLSA score after subjects adjust hearing aid with MyPhonak Junior App | At the first face-to-face the subject will be trained on the app, and complete the OLSA. After 2 week home trial, the OLSA will be re-administered to see if the adjustments the subjects made using the MyPhonak Junior app impacted speech intelligibility, which would be shown by the OLSA score at the second face-to-face visit. | 4 weeks for each subject (2 face-to-face visits + 2 weeks home trial), 12 months in total for study to be completed |
|
Hearing Loss, Hearing Disorders, Ear Diseases, Otorhinolaryngologic Diseases, Sensation Disorders, Neurologic Manifestations, Nervous System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Study Group<br>It is a prospective study to investigate whether the MyPhonak Junior app can improve speech understanding in children with hearing aids, by evaluating the use of the volume, noise reduction and directional microphone using the MyPhonak Junior App.. The study is linked to randomized patient and test allocation carried out.~Introduction to the MyPhonak Junior app. There are measurements of speech understanding of sentences Carried out in background noise with the Oldenburg sentence test (OLSA). The language test is hard of hearing children and adolescents known from routine clinical practice. Various everyday situations / noise scenarios are played out. Questionnaire (E-HAK, also known from routine) and interview of the children regarding the use of the app in everyday life. | Device: MyPhonak Junior App<br>* The primary objective is to evaluate the effects on speech intelligibility of resulting from the changes that children and adolescents (aged 7 to 17 years) make to the volume control, directionality and noise reduction of the hearing of the hearing aids using the myPhonak app. First, in a controlled laboratory environment under the guidance of the principal investigator is tested. Then, using sound scenarios, the child is allowed to try out two programs with the aid of using the app and the volume control, respectively. After this, the speech comprehension of sentences in noise is tested in the individual programs using the Oldenburg Sentence Test (OLSA).<br>|
|
MyPhonak App Junior Pediatric Usability and Benefit Investigation
Study Overview
=================
Brief Summary
-----------------
ESolutions functions for children and young people with the myPhonak app is a prospective study to investigate whether the myPhonak app can improve speech understanding in children with hearing aids. The study is linked to randomized patient and test allocation carried out.
Official Title
-----------------
ESolutions Functions for Children and Young People With the myPhonak App
Conditions
-----------------
Hearing Loss
Intervention / Treatment
-----------------
* Device: MyPhonak Junior App
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Children and adolescents between the ages of 7 and 17 years old. With normal middle ear characteristics With a hearing impairment in the mild to severe range With adequate speech development Exclusion Criteria: Unreliability and lack of cooperation exists, An effusion in the middle ear or local inflammation in the ear canal or middle ear with/without a running ear, Mental limitations, If the patient is unable to operate a smartphone, Other objections to study participation in the opinion of the study director exist.
Ages Eligible for Study
-----------------
Minimum Age: 7 Years
Maximum Age: 17 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Study Group<br>It is a prospective study to investigate whether the MyPhonak Junior app can improve speech understanding in children with hearing aids, by evaluating the use of the volume, noise reduction and directional microphone using the MyPhonak Junior App.. The study is linked to randomized patient and test allocation carried out. Introduction to the MyPhonak Junior app. There are measurements of speech understanding of sentences Carried out in background noise with the Oldenburg sentence test (OLSA). The language test is hard of hearing children and adolescents known from routine clinical practice. Various everyday situations / noise scenarios are played out. Questionnaire (E-HAK, also known from routine) and interview of the children regarding the use of the app in everyday life. | Device: MyPhonak Junior App<br>* The primary objective is to evaluate the effects on speech intelligibility of resulting from the changes that children and adolescents (aged 7 to 17 years) make to the volume control, directionality and noise reduction of the hearing of the hearing aids using the myPhonak app. First, in a controlled laboratory environment under the guidance of the principal investigator is tested. Then, using sound scenarios, the child is allowed to try out two programs with the aid of using the app and the volume control, respectively. After this, the speech comprehension of sentences in noise is tested in the individual programs using the Oldenburg Sentence Test (OLSA).<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in OLSA score after subjects adjust hearing aid with MyPhonak Junior App | At the first face-to-face the subject will be trained on the app, and complete the OLSA. After 2 week home trial, the OLSA will be re-administered to see if the adjustments the subjects made using the MyPhonak Junior app impacted speech intelligibility, which would be shown by the OLSA score at the second face-to-face visit. | 4 weeks for each subject (2 face-to-face visits + 2 weeks home trial), 12 months in total for study to be completed |
|
|||
NCT03112577
|
Study of REGN3500 and Dupilumab in Patients With Asthma
|
To assess the effects of REGN3500, dupilumab, and REGN3500 plus dupilumab, compared with placebo, on changes in inflammatory gene expression signatures in sputum induced after a bronchial allergen challenge (BAC) in adults with mild allergic asthma, at week 4 after treatment initiation compared with those at screening.
|
A Randomized, Placebo-controlled, Parallel Panel Study to Assess the Effects of REGN3500, Dupilumab, and Combination of REGN3500 Plus Dupilumab on Markers of Inflammation After Bronchial Allergen Challenge in Patients With Allergic Asthma
|
Asthma, Allergic
|
* Drug: REGN3500
* Drug: Dupilumab
* Drug: Placebo
* Drug: Fluticasone propionate
|
KEY Inclusion Criteria:~Male or female aged between 18 and 60 years~Has a Body Mass Index {BMI) of 17 to 33 kg/m2 at pre-study screening~Has a history of mild allergic asthma for at least 6 months~Is a non-smoker or ex-smoker for at least 12 months~KEY Exclusion Criteria:~Has a history of life-threatening asthma~Has been hospitalized or has attended the emergency room for asthma in the 12 months prior to screening~Has a history of severe allergies or history of an anaphylactic reaction~Has a history of drug or alcohol abuse within a year prior to the screening visit~Note: other protocol defined inclusion/exclusion criteria apply
|
18 Years
|
60 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in bronchial allergen challenge (BAC)-induced changes in sputum inflammatory markers in individuals treated with REGN3500, dupilumab and the combination of REGN3500 plus dupilumab or placebo | | Screening (pre-treatment) to week 4 after treatment initiation |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment Emergent Adverse Events (TEAEs) | | Baseline to week 42 |
| Severity of TEAEs | | Baseline to week 42 |
| Serum concentration-time profile of REGN3500 | Assessed by maximum plasma concentration [Cmax] | Baseline to week 42 |
| Serum concentration-time profile of REGN3500: Tmax (time at Cmax) | | Baseline to week 42 |
| Serum concentration-time profile of REGN3500: AUClast (area under the curve to the last measurable concentration) | | Baseline to week 42 |
| Immunogenicity of REGN3500 and dupilumab | Assessed by measurement of anti-drug antibodies (ADAs) | Baseline to week 42 |
| Serum concentration of total IL-33 after single IV dose | | Up to Week 42 |
| Difference in the BAC-induced changes in sputum inflammatory mRNA signature in individual patients treated with fluticasone | | Screening (pre-treatment) to day 4 after treatment initiation |
|
Xhance, Fluticasone, Anti-Inflammatory Agents, Bronchodilator Agents, Autonomic Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Anti-Asthmatic Agents, Respiratory System Agents, Dermatologic Agents, Anti-Allergic Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: REGN3500<br>REGN3500: masked and randomized dosing regimen per protocol (part 1 only) | Drug: REGN3500<br>* Intravenous (IV) use<br>|
| Experimental: Dupilumab<br>Dupilumab: masked and randomized dosing regimen per protocol (part 1 only) | Drug: Dupilumab<br>* Subcutaneous (SC) use<br>* Other names: Dupixent;|
| Experimental: REGN3500 plus dupilumab<br>REGN3500 plus dupilumab: masked and randomized dosing regimen per protocol (part 1 only) | Drug: REGN3500<br>* Intravenous (IV) use<br>Drug: Dupilumab<br>* Subcutaneous (SC) use<br>* Other names: Dupixent;|
| Experimental: Placebo<br>Placebo: masked and randomized dosing regimen per protocol (part 1 only) | Drug: Placebo<br>* Matching placebo<br>|
| Active Comparator: Fluticasone propionate<br>Fluticasone propionate: open label dosing regimen per protocol (part 2 only) | Drug: Fluticasone propionate<br>* Inhalation use<br>|
|
Study of REGN3500 and Dupilumab in Patients With Asthma
Study Overview
=================
Brief Summary
-----------------
To assess the effects of REGN3500, dupilumab, and REGN3500 plus dupilumab, compared with placebo, on changes in inflammatory gene expression signatures in sputum induced after a bronchial allergen challenge (BAC) in adults with mild allergic asthma, at week 4 after treatment initiation compared with those at screening.
Official Title
-----------------
A Randomized, Placebo-controlled, Parallel Panel Study to Assess the Effects of REGN3500, Dupilumab, and Combination of REGN3500 Plus Dupilumab on Markers of Inflammation After Bronchial Allergen Challenge in Patients With Allergic Asthma
Conditions
-----------------
Asthma, Allergic
Intervention / Treatment
-----------------
* Drug: REGN3500
* Drug: Dupilumab
* Drug: Placebo
* Drug: Fluticasone propionate
Participation Criteria
=================
Eligibility Criteria
-----------------
KEY Inclusion Criteria: Male or female aged between 18 and 60 years Has a Body Mass Index {BMI) of 17 to 33 kg/m2 at pre-study screening Has a history of mild allergic asthma for at least 6 months Is a non-smoker or ex-smoker for at least 12 months KEY Exclusion Criteria: Has a history of life-threatening asthma Has been hospitalized or has attended the emergency room for asthma in the 12 months prior to screening Has a history of severe allergies or history of an anaphylactic reaction Has a history of drug or alcohol abuse within a year prior to the screening visit Note: other protocol defined inclusion/exclusion criteria apply
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: REGN3500<br>REGN3500: masked and randomized dosing regimen per protocol (part 1 only) | Drug: REGN3500<br>* Intravenous (IV) use<br>|
| Experimental: Dupilumab<br>Dupilumab: masked and randomized dosing regimen per protocol (part 1 only) | Drug: Dupilumab<br>* Subcutaneous (SC) use<br>* Other names: Dupixent;|
| Experimental: REGN3500 plus dupilumab<br>REGN3500 plus dupilumab: masked and randomized dosing regimen per protocol (part 1 only) | Drug: REGN3500<br>* Intravenous (IV) use<br>Drug: Dupilumab<br>* Subcutaneous (SC) use<br>* Other names: Dupixent;|
| Experimental: Placebo<br>Placebo: masked and randomized dosing regimen per protocol (part 1 only) | Drug: Placebo<br>* Matching placebo<br>|
| Active Comparator: Fluticasone propionate<br>Fluticasone propionate: open label dosing regimen per protocol (part 2 only) | Drug: Fluticasone propionate<br>* Inhalation use<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in bronchial allergen challenge (BAC)-induced changes in sputum inflammatory markers in individuals treated with REGN3500, dupilumab and the combination of REGN3500 plus dupilumab or placebo | | Screening (pre-treatment) to week 4 after treatment initiation |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment Emergent Adverse Events (TEAEs) | | Baseline to week 42 |
| Severity of TEAEs | | Baseline to week 42 |
| Serum concentration-time profile of REGN3500 | Assessed by maximum plasma concentration [Cmax] | Baseline to week 42 |
| Serum concentration-time profile of REGN3500: Tmax (time at Cmax) | | Baseline to week 42 |
| Serum concentration-time profile of REGN3500: AUClast (area under the curve to the last measurable concentration) | | Baseline to week 42 |
| Immunogenicity of REGN3500 and dupilumab | Assessed by measurement of anti-drug antibodies (ADAs) | Baseline to week 42 |
| Serum concentration of total IL-33 after single IV dose | | Up to Week 42 |
| Difference in the BAC-induced changes in sputum inflammatory mRNA signature in individual patients treated with fluticasone | | Screening (pre-treatment) to day 4 after treatment initiation |
|
||
NCT01667289
|
Radiotherapy Alone Versus Concurrent Chemoradiation in Low Risk NK/T-cell Lymphoma
|
The purpose of this study is to prove the superiority of concurrent chemoradiation compared with radiotherapy alone in patients with low risk NK/T-cell lymphoma.
|
Radiotherapy alone is commonly used in NK/T-cell lymphoma without adverse risk including lymph node involvement, local invasion, B symptoms and high LDH level. Recently, methotrexate was prove to be a radiosensitizer in NK/T-cell lymphoma cells. Therefore, the investigators aim to verify the superiority and safety of weekly methotrexate in combination with radiotherapy in a randomized phase II study.
|
A Randomized Phase II Study of Comparing Radiotherapy Alone With Concurrent Chemoradiation in Patients With Low Risk NK/T-cell Lymphoma
|
Extranodal NK/T-cell Lymphoma, Nasal Type
|
* Radiation: Radiotherapy alone
* Drug: Concurrent chemoradiation
|
Inclusion Criteria:~Age range 18-75 years old~Histological confirmed, previously untreated stage IE nasal NK/T cell lymphoma without following risk factors including local invasion, B symptoms and high LDH level~ECOG performance status 0-1~Life expectancy of more than 3 months~Adequate bone marrow and organ functions~Exclusion Criteria:~non-nasal NK/T-cell lymphoma~Prior exposure of methotrexate~With third space effusion~Pregnant or lactating women~Serious uncontrolled diseases and intercurrent infection~History of other malignancies except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix
|
18 Years
|
75 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year Progression-free survival | | 3 years |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate | | 3 years |
| 3-year overall survival | | 3 years |
|
NK/T-cell lymphoma, Methotrexate, Radiotherapy, Concurrent chemoradiation
|
Lymphoma, Lymphoma, T-Cell, Lymphoma, T-Cell, Peripheral, Lymphoma, Extranodal NK-T-Cell, Neoplasms by Histologic Type, Neoplasms, Lymphoproliferative Disorders, Lymphatic Diseases, Immunoproliferative Disorders, Immune System Diseases, Lymphoma, Non-Hodgkin
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Radiotherapy alone<br>Radiotherapy alone Technique: IMRT Total Dose: 50 Gy Per fraction: 2 Gy | Radiation: Radiotherapy alone<br>* Radiotherapy alone Technique: IMRT Total Dose: 50 Gy Per fraction: 2 Gy<br>|
| Experimental: Concurrent chemoradiation<br>Concurrent chemoradiation~Chemotherapy:~Methotrexate 40 mg/m2 weekly X 5 Radiotherapy Technique: IMRT Total dose: 50 Gy Per Fraction: 2 Gy | Radiation: Radiotherapy alone<br>* Radiotherapy alone Technique: IMRT Total Dose: 50 Gy Per fraction: 2 Gy<br>Drug: Concurrent chemoradiation<br>* Concurrent chemoradiation~Chemotherapy:~Methotrexate 40 mg/m2 weekly X 5 Radiotherapy Technique: IMRT Total dose: 50 Gy Per Fraction: 2 Gy<br>* Other names: MTX;|
|
Radiotherapy Alone Versus Concurrent Chemoradiation in Low Risk NK/T-cell Lymphoma
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to prove the superiority of concurrent chemoradiation compared with radiotherapy alone in patients with low risk NK/T-cell lymphoma.
Detailed Description
-----------------
Radiotherapy alone is commonly used in NK/T-cell lymphoma without adverse risk including lymph node involvement, local invasion, B symptoms and high LDH level. Recently, methotrexate was prove to be a radiosensitizer in NK/T-cell lymphoma cells. Therefore, the investigators aim to verify the superiority and safety of weekly methotrexate in combination with radiotherapy in a randomized phase II study.
Official Title
-----------------
A Randomized Phase II Study of Comparing Radiotherapy Alone With Concurrent Chemoradiation in Patients With Low Risk NK/T-cell Lymphoma
Conditions
-----------------
Extranodal NK/T-cell Lymphoma, Nasal Type
Intervention / Treatment
-----------------
* Radiation: Radiotherapy alone
* Drug: Concurrent chemoradiation
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age range 18-75 years old Histological confirmed, previously untreated stage IE nasal NK/T cell lymphoma without following risk factors including local invasion, B symptoms and high LDH level ECOG performance status 0-1 Life expectancy of more than 3 months Adequate bone marrow and organ functions Exclusion Criteria: non-nasal NK/T-cell lymphoma Prior exposure of methotrexate With third space effusion Pregnant or lactating women Serious uncontrolled diseases and intercurrent infection History of other malignancies except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Radiotherapy alone<br>Radiotherapy alone Technique: IMRT Total Dose: 50 Gy Per fraction: 2 Gy | Radiation: Radiotherapy alone<br>* Radiotherapy alone Technique: IMRT Total Dose: 50 Gy Per fraction: 2 Gy<br>|
| Experimental: Concurrent chemoradiation<br>Concurrent chemoradiation Chemotherapy: Methotrexate 40 mg/m2 weekly X 5 Radiotherapy Technique: IMRT Total dose: 50 Gy Per Fraction: 2 Gy | Radiation: Radiotherapy alone<br>* Radiotherapy alone Technique: IMRT Total Dose: 50 Gy Per fraction: 2 Gy<br>Drug: Concurrent chemoradiation<br>* Concurrent chemoradiation Chemotherapy: Methotrexate 40 mg/m2 weekly X 5 Radiotherapy Technique: IMRT Total dose: 50 Gy Per Fraction: 2 Gy<br>* Other names: MTX;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year Progression-free survival | | 3 years |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate | | 3 years |
| 3-year overall survival | | 3 years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
NK/T-cell lymphoma, Methotrexate, Radiotherapy, Concurrent chemoradiation
|
NCT05613595
|
Effectiveness of Positive Psychotherapy on Mental Wellbeing Among Caregivers of Cerebral Palsy Children
|
The Central idea of the proposed research proposal is first to translate adapt and validate the Caregiver Difficulties Scale & Positive Psychotherapy sessions based manual into Urdu language then secondly, assessment of burnout, burden, depression, mental wellbeing, sense of coherence and social support among caregivers of Cerebral palsy children and finally measuring the effectiveness of Positive Psychotherapy for treating mental health issues of caregivers of Cerebral Palsy children. This research proposal will provide an Urdu language based standardized positive psycho therapeutic based intervention to mental health practitioners for treating mental health issues of caregivers of cerebral palsy children in sociocultural context of Pakistan. In Pakistan earlier conducted researches mainly focused on assessment of mental health issues of caregivers of cerebral palsy children, however present research will not only assess the sample regarding their mental health issues, but in addition it will also contribute in provision of psychometrically sound Urdu language based positive Psychotherapy. Positive Psychotherapy focuses on positive emotions and personal strengths instead of ruminating over weaknesses.
|
Cerebral palsy (CP) is a congenital neurodevelopmental disorder, due to non-progressive disability it prolongs throughout ages. Mental health of the caregivers of CP children is affected due to prolong treatment of the child. Keeping in mind the long term multiple disability in cerebral palsy much focus in earlier researches were given to the rehabilitation of the child and less attention is given to address the mental health issues of caregivers of cerebral palsy children. The current study is based on identifying the mental health issues like depression, caregiver burden and burnout among caregivers of CP children and how sense of coherence and social support have impact on the mental wellbeing of caregivers of CP children. After measuring the level of mental health issues of care givers of cerebral palsy children, the present study also aimed at rehabilitation of the caregivers of cerebral palsy children with the help of positive psychotherapy in rehabilitation unit. The positive psychotherapy based interventions will be translated and adapted in Urdu language for the present study. According to the literature review no such positive psychotherapy based techniques used on caregivers of CP Children in Pakistan. Positive Psychotherapy is selected as an interventional therapy in the present study and for the first time it has been planned for this sample in Pakistan. Core focus of positive psychotherapy is to move away the client from negative aspect of life and focus them towards the positive aspects of life. If positive psychotherapy treatment is effective as compared to traditional treatment approach it will be cost effective and will reduce caregiver burden, depression and burnout.
|
Effectiveness of Positive Psychotherapy on Mental Wellbeing, Sense of Coherence, Social Support and Difficulties Among Caregivers of Cerebral Palsy Children
|
Caregiver Burden, Mental Health Issue, Cerebral Palsy
|
* Behavioral: Positive Psychotherapy
* Behavioral: Counseling Group
|
Inclusion Criteria:~Only those participants will be included who would have moderate to high score on caregiver burden, depression & burnout and lower score in wellbeing, social support & sense of coherence.~Interventions will be given to the caregivers having moderate level of burnout & depression.~Inclusion Criteria~Caregiver will be someone who takes the primary responsibility for caregiving a child with CP.~Only caregivers of Diagnosed CP child~Caregivers having only 1 CP child in the family~Educational status of the care giver will be matric and above.~Age of CP child under 10 years Exclusion Criteria:• Caregivers with any severe diagnosed Psychiatric illness (psychosis & depressive Illness) will not be added in the present study.~More than 1 CP child in the family~Caregivers who are Uneducated will not be added in the present study.
|
25 Years
|
50 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Present study will be conducted on caregivers of Cerebral palsy children. It will be conducted in four phases. In phase I, Urdu translation & adaptation of Caregiver Difficulties Scale (CDS) and Positive Psychotherapy (PPT) manual will be done. .
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Parental Burnout Assessment | a 23- item self-report questionnaire for assessment of Burn Out | baseline and 8th week |
| Change in Depression Anxiety Stress Scale | DASS is a self-report 21 items based questionnaire designed to measure depression, anxiety and stress | baseline and 8th week |
| Change in Caregiver Difficulties Scale | a self-administered questionnaire measure the caregiver burden | baseline and 8th week |
| Change in Sense of Coherence | Measured by the orientation of life scale, It contains 13 items | baseline and 8th week |
| Change in wellbeing Positive Psychotherapy Inventory | self-report inventory having 25 items.it assess level of mental wellbeing, | baseline and 8th week |
| Change Multidimensional Scale of Perceived Social Support | Social support is measured across three domains; friends, family and significant others. The responses reflect participant's perception of support from each of these three sources | baseline and 8th week |
|
Positive psychotherapy, Sense of Coherence, Social support
|
Cerebral Palsy, Caregiver Burden, Nervous System Diseases, Brain Damage, Chronic, Brain Diseases, Central Nervous System Diseases, Stress, Psychological, Behavioral Symptoms
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Positive Psychotherapy Group<br>In this phase of the study, the caregivers of CP having moderate to high scores on mental health issues on three scales (Depression, Burnout & Caregiver burden) will receive positive Psychotherapy sessions for a period of four months, divided over different weekly sessions. For Psychotherapy treatment group participants will be given both counseling as well as Positive psychotherapy based interventions. . Each session will be based upon individual session and duration of the session will be 40 minutes. Before starting every session feedback will be taken about the previous session and home based assignments will also be discussed | Behavioral: Positive Psychotherapy<br>* Positive Psychotherapy is an effective treatment for many mental disorders and depression is primary empirical target. Its primary goal is to build positive emotion, engagement, and meaning in life that will alleviate depression and other mental health disorders. Thus PPT may offer a new way to treat and prevent mental health issues.~Interventions sessions included, Session Records Session One: Positive Introduction and Gratitude Journal Session Two: Character Strengths and Signature Strengths Session Three: Practical Wisdom , Session Four: A Better Version of Me , Session Five: Open and Closed Memories, Session Six: Forgiveness Session Seven: Maximizing versus Satisficing, Session Eight: Gratitude ,Session Nine: Hope and Optimism, Session Ten: Posttraumatic Growth, Session Eleven: Slowness and Savoring, Session Twelve: Positive Relationships, Session Thirteen: Positive Communication, Session Fourteen: Altruism , Session Fifteen: Meaning and Purpose<br>|
| Active Comparator: Counseling Group<br>10 participants will be included in in control group (N=10), for control group caregivers will be given regular counseling as a part of treatment of their child (psychoeducation). Each session will be based upon individual session and duration of the session will be 40 minutes. | Behavioral: Counseling Group<br>* Caregivers in control group only regular counseling will be provided (psychoeducation). it will be based upon the insight of cerebral palsy and training based on Adaptive skill functioning of the CP child of the caregivers<br>|
|
Effectiveness of Positive Psychotherapy on Mental Wellbeing Among Caregivers of Cerebral Palsy Children
Study Overview
=================
Brief Summary
-----------------
The Central idea of the proposed research proposal is first to translate adapt and validate the Caregiver Difficulties Scale & Positive Psychotherapy sessions based manual into Urdu language then secondly, assessment of burnout, burden, depression, mental wellbeing, sense of coherence and social support among caregivers of Cerebral palsy children and finally measuring the effectiveness of Positive Psychotherapy for treating mental health issues of caregivers of Cerebral Palsy children. This research proposal will provide an Urdu language based standardized positive psycho therapeutic based intervention to mental health practitioners for treating mental health issues of caregivers of cerebral palsy children in sociocultural context of Pakistan. In Pakistan earlier conducted researches mainly focused on assessment of mental health issues of caregivers of cerebral palsy children, however present research will not only assess the sample regarding their mental health issues, but in addition it will also contribute in provision of psychometrically sound Urdu language based positive Psychotherapy. Positive Psychotherapy focuses on positive emotions and personal strengths instead of ruminating over weaknesses.
Detailed Description
-----------------
Cerebral palsy (CP) is a congenital neurodevelopmental disorder, due to non-progressive disability it prolongs throughout ages. Mental health of the caregivers of CP children is affected due to prolong treatment of the child. Keeping in mind the long term multiple disability in cerebral palsy much focus in earlier researches were given to the rehabilitation of the child and less attention is given to address the mental health issues of caregivers of cerebral palsy children. The current study is based on identifying the mental health issues like depression, caregiver burden and burnout among caregivers of CP children and how sense of coherence and social support have impact on the mental wellbeing of caregivers of CP children. After measuring the level of mental health issues of care givers of cerebral palsy children, the present study also aimed at rehabilitation of the caregivers of cerebral palsy children with the help of positive psychotherapy in rehabilitation unit. The positive psychotherapy based interventions will be translated and adapted in Urdu language for the present study. According to the literature review no such positive psychotherapy based techniques used on caregivers of CP Children in Pakistan. Positive Psychotherapy is selected as an interventional therapy in the present study and for the first time it has been planned for this sample in Pakistan. Core focus of positive psychotherapy is to move away the client from negative aspect of life and focus them towards the positive aspects of life. If positive psychotherapy treatment is effective as compared to traditional treatment approach it will be cost effective and will reduce caregiver burden, depression and burnout.
Official Title
-----------------
Effectiveness of Positive Psychotherapy on Mental Wellbeing, Sense of Coherence, Social Support and Difficulties Among Caregivers of Cerebral Palsy Children
Conditions
-----------------
Caregiver Burden, Mental Health Issue, Cerebral Palsy
Intervention / Treatment
-----------------
* Behavioral: Positive Psychotherapy
* Behavioral: Counseling Group
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Only those participants will be included who would have moderate to high score on caregiver burden, depression & burnout and lower score in wellbeing, social support & sense of coherence. Interventions will be given to the caregivers having moderate level of burnout & depression. Inclusion Criteria Caregiver will be someone who takes the primary responsibility for caregiving a child with CP. Only caregivers of Diagnosed CP child Caregivers having only 1 CP child in the family Educational status of the care giver will be matric and above. Age of CP child under 10 years Exclusion Criteria:• Caregivers with any severe diagnosed Psychiatric illness (psychosis & depressive Illness) will not be added in the present study. More than 1 CP child in the family Caregivers who are Uneducated will not be added in the present study.
Ages Eligible for Study
-----------------
Minimum Age: 25 Years
Maximum Age: 50 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Present study will be conducted on caregivers of Cerebral palsy children. It will be conducted in four phases. In phase I, Urdu translation & adaptation of Caregiver Difficulties Scale (CDS) and Positive Psychotherapy (PPT) manual will be done. .
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Positive Psychotherapy Group<br>In this phase of the study, the caregivers of CP having moderate to high scores on mental health issues on three scales (Depression, Burnout & Caregiver burden) will receive positive Psychotherapy sessions for a period of four months, divided over different weekly sessions. For Psychotherapy treatment group participants will be given both counseling as well as Positive psychotherapy based interventions. . Each session will be based upon individual session and duration of the session will be 40 minutes. Before starting every session feedback will be taken about the previous session and home based assignments will also be discussed | Behavioral: Positive Psychotherapy<br>* Positive Psychotherapy is an effective treatment for many mental disorders and depression is primary empirical target. Its primary goal is to build positive emotion, engagement, and meaning in life that will alleviate depression and other mental health disorders. Thus PPT may offer a new way to treat and prevent mental health issues. Interventions sessions included, Session Records Session One: Positive Introduction and Gratitude Journal Session Two: Character Strengths and Signature Strengths Session Three: Practical Wisdom , Session Four: A Better Version of Me , Session Five: Open and Closed Memories, Session Six: Forgiveness Session Seven: Maximizing versus Satisficing, Session Eight: Gratitude ,Session Nine: Hope and Optimism, Session Ten: Posttraumatic Growth, Session Eleven: Slowness and Savoring, Session Twelve: Positive Relationships, Session Thirteen: Positive Communication, Session Fourteen: Altruism , Session Fifteen: Meaning and Purpose<br>|
| Active Comparator: Counseling Group<br>10 participants will be included in in control group (N=10), for control group caregivers will be given regular counseling as a part of treatment of their child (psychoeducation). Each session will be based upon individual session and duration of the session will be 40 minutes. | Behavioral: Counseling Group<br>* Caregivers in control group only regular counseling will be provided (psychoeducation). it will be based upon the insight of cerebral palsy and training based on Adaptive skill functioning of the CP child of the caregivers<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Parental Burnout Assessment | a 23- item self-report questionnaire for assessment of Burn Out | baseline and 8th week |
| Change in Depression Anxiety Stress Scale | DASS is a self-report 21 items based questionnaire designed to measure depression, anxiety and stress | baseline and 8th week |
| Change in Caregiver Difficulties Scale | a self-administered questionnaire measure the caregiver burden | baseline and 8th week |
| Change in Sense of Coherence | Measured by the orientation of life scale, It contains 13 items | baseline and 8th week |
| Change in wellbeing Positive Psychotherapy Inventory | self-report inventory having 25 items.it assess level of mental wellbeing, | baseline and 8th week |
| Change Multidimensional Scale of Perceived Social Support | Social support is measured across three domains; friends, family and significant others. The responses reflect participant's perception of support from each of these three sources | baseline and 8th week |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Positive psychotherapy, Sense of Coherence, Social support
|
|
NCT05487482
|
Model for Safety Culture by Empowering the Family at Home: a Mixed-methods Study Protocol
|
Background: The elderly are a vulnerable group for health problems as they age. Safe care is essential when caring for the elderly at home because adverse events can happen there, such as falls, pressure ulcers, injuries, or dangers caused by medication errors. Safety culture for the elderly at home needs to be developed so that they can avoid unexpected events. This study aimed to develop the model for safety culture among the elderly called Aging Safe from the Risk (ASRi) to improve the safety culture in elderly care at home.~Methods: This exploratory sequential mixed methods study will consist of three stages. Stage 1, a qualitative descriptive study, will be conducted to explore the perceptions of families, nurses, and school administrators for the elderly regarding the safety of the elderly at home. Data will be collected by interviews and focus group discussions. Stage II will involve developing The ASRi model using the modified Delphi method. The list of elderly safety culture indicators will be assessed by experts and then further developed into a model. In stage III, a model test will be conducted with a non-equivalent control group using a quasi-experimental design. The investigators will provide interventions in the form of education and training to families regarding the safety culture for the elderly at home.~Findings: There is a crucial need for studies assessing the safety culture in elderly care by empowering families at home to improve safety for the elderly. The results of this study will help fill the knowledge gap in this research and can aid in developing public health policy and programs for the elderly.~.
|
This study aims to obtain a model of elderly safety culture by involving families in self-care at home to increase perceptions of safety culture and reduce adverse events at home. The specific aims are:~Exploring the perceptions of families, healthcare providers, and elderly school administrators regarding the safety of the elderly at home;~Develop the Ageing Safe from the Risk (ASRi) model of safety culture; and~Conducting trials of applying the ASRi model to improve the perception of the elderly safety culture and reduce adverse events at home.~This protocol have been approval from the Medical and Health Research Ethics Committee of the Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada-Dr. Sardjito General Hospital with the number KE/FK/0632/EC/2021 on the date in 10 June 2021.~Study design This exploratory sequential mixed methods will include three stages, and the quantitative design will be the most dominant in this research. Setting This study will be conducted in Bandung, the capital city of West Java, Indonesia. Bandung has 30 subdistricts, and there are 4 subdistricts that have elderly schools. Elderly schools in Bandung have 275 members and are managed by Elderly Friends. The elderly school model was established in 2019 developed by Indonesia Ramah Lansia (IRL) West Java. Activities at the Bandung Elderly School include education about elderly health concerns and home visits by Elderly Friends to monitor the health of the elderly at home.~Study stages and data collection Stage I (Qualitative Study) In the first stage, the descriptive exploratory will be used to explore the perceptions of families, the elderly, healthcare providers, and school administrators regarding the safety of the elderly at home.~Data collection will be conducted with in-depth interviews with the elderly and families and focus group discussions (FGD) among the healthcare providers and elderly school managers In-depth interviews will be conducted to obtain complete information about perceptions of families and elderly about their safety, especially in four dimensions: the personal dimensions including family values/beliefs about the safety of the elderly, understanding, attitudes and family motivations towards the safety of the elderly; behavioral dimensions including communication patterns, cooperation, family stress and burden; and environmental dimensions including family efforts in creating a safe environment for the elderly. The interview guides (shown in Appendix 1) which contain open-ended questions and probes to explore the perceptions about safety in elderly care will be tested in pilot study. To increase credibility, researchers will use data triangulation by also observing the conditions of the elderly home. Furthermore, will also conduct interviews about the hopes and needs of families related to the safety of the elderly at home. Data collection also will be done among the elderly to obtain information about the experiences related to safety and security and their expectations regarding their safety at home.~Interviews will be conducted face-to-face at participants' homes. Each in-depth interview and FGD will take between 60-90 minutes. In-depth interviews will be terminated when there is no additional information needed anymore (data saturation). In this pandemic period, the invesitagors will apply health protocols when conducting interviews, by using masks, maintaining safe distance, and ensuring the conditions of researchers and participants are in good health. The FGDs will be conducted in two groups: with healthcare providers and with administrators of elderly schools in four sub-district areas. FGDs will be held by the agreements of the participants, whether offline or online.~Before the interviews, participants will provide their sociodemographic and related information such as age, education, occupation and race. Information about this research will be explained to all participants before they are required to sign an informed consent form. All interviews will be conducted in Indonesian or Sundanese language and audio-recorded. All data in Sundanese language will be translated into Indonesian.~Stage 2 (Quantitative Study) In the second stage, the investigators will conduct Delphi methods with some modification (30) to find out indicator drafts that can be used to develop the ASRi Model. Modifications from the implementation of Delphi will be in stage 1 when researchers directly provide a list of indicators based on the results of the phase 1 study. In addition, in stage two the panel discussions will be conducted online or offline depending on the willingness of the experts. The Delphi methods modification will be done in two rounds. In the first round of Delphi, the investigators will compile a list of statement items that are indicators of the elderly safety culture at home based on the results of the first stage. Informed consent will be obtained from all participants at the first round. The investigators will contact the experts individually by phone or email to explain the purpose of research and implementation of Delphi. Then, the experts will be asked to provide an assessment of indicators in the safety culture of the elderly at home. The investigators will allocate two weeks for Delphi experts to respond in the first round. Reminders will be sent to participants one week before each round begins in order to maximize their participation. Then, we will process and refine the findings according to the assessment of the Delphi first round.~Next, the Delphi second round will do by conducting expert panel discussions. The investigators will invite experts for discussions regarding the results of the first round of Delphi. Discussions will be conducted both online and offline (hybrid). All indicators resulting from the first round will be discussed in this expert panel. The results of the second round of Delphi will be developed into the ASRi model of safety culture in the elderly.~Stage 3 (Quantitative Study) The third stage, testing the model will be done by conducting a quasi-experimental study with a non-equivalent control group using a pre-posttest design. The intervention Ageing Safe from the Risk (ASRi) will consist of about 16 weeks. First, the investigators will conduct training of trainers to nurses and elderly friends. They will be given modules. At this stage, the investigators will also prepare for the control groups and intervention groups. Selection of control and intervention groups based on geographical locations.~Two research assistants, with minimum education of bachelor nursing, will conduct a survey for pre-test measurements and make home visits in each groups. Previously, the investigators will explain about filling out the questionnaire to the research assistants.~For the intervention groups, planning will be done to provide education and training. Families will be given modules on Safety Culture in the Elderly. Materials provided about the safety of the elderly include changes in the elderly, the concept of safety in the elderly, the type of danger to the elderly, how to prevent harm in the elderly, the first handling in case of accidents, and the role of the family in the efforts of elderly safety. The material will be delivered by experts in elderly health and patient safety (professionals from health centers, social services, and academics). In addition to education and training, families will also receive home visits to check and monitoring the condition of the elderly at home related to adverse events and the home environment. Measuring will be done every 2 weeks by using a monitoring book.~In the control groups, activities as usual will be carried out by the elderly friends. After 16 weeks, researchers will evaluate perceptions of the elderly's safety culture at home and adverse events at home.~STUDY POPULATION Participants Stage I (Qualitative study) The qualitative study aims to explore the perceptions of family, elderly, healthcare providers, and administrators of elderly schools about safety in the elderly. This study will conduct individual interviews for family and the elderly, and FGD for healthcare providers and administrators of elderly schools.~This study will include the elderly and their families who are members of the elderly schools in Bandung, healthcare providers from the Public Health Centers, and administrators of elderly schools in Bandung. The sampling technique will use purposive sampling and maximum variation. Inclusion criteria for elderly are: living with family; level of independence are independent, mild and moderate based on Barthel Index [31], no impaired cognitive function, and communication.~Inclusion criteria for the family are: family members who live with the elderly and age at least 18 years old or more. Inclusion criteria for healthcare providers are: minimum education background of diploma with one year of work experience in caring for elderly. Inclusion criteria for elderly school administrators are: manager of The Indonesia Ramah Lansia (IRL) West Java who manages elderly schools in Bandung, and administrators of elderly schools and active in managing elderly schools. There are four elderly schools in Bandung, and each elderly school will involve two administrators.~Stage II (Quantitative study with Delphi method) Purpose of study is to develop the Ageing Safe from the Risk (ASRi) model of safety culture. The subjects in this stage II study are experts in elderly nursing, family nursing, patient safety, and stakeholders related to elderly health programs. Criteria of experts in this study are: geriatric doctors with experience caring for elderly at home; healthcare providers in elderly programs; elderly school managers; managers of IRL West Java; lecturers in family nursing, gerontics and patient safety; families who have experience caring for the elderly, and stakeholders from social services and National Population and Family Planning Board.~Stage III (Quantitative study) The purpose of the study is to test the ASRi model in improving perceptions of safety culture and decreasing adverse events in the elderly at home. At this stage of the study, the population is the elderly and family members of the Bandung City Elderly School in 2020. The sample in this study are the elderly and families who are members of elderly schools in Bandung. Purposive sampling will be used to recruit the samples. Inclusion criteria for the elderly are: living with family; have a history of adverse events over the past one year such as falls, pressure ulcers, injuries, and problems due to treatment; can communicate effectively, and have a level of dependence: independent, mild, and moderate. Inclusion criteria for family are: taking care of the elderly directly, can communicate effectively, and have a minimum age of 18 years. Withdrawal criteria: family did not continue the study, elderly were hospitalized, and died during the study.~Sampling methods and sample size Stage I (Qualitative study) The sampling technique will use purposive sampling. The investigators (AHS) will recruit participants for individual interviewing in subdistrict Central Antapani, Sukajadi, Ujung Berung and Cinambo based on the inclusion criteria. First, investigators will contact the Elderly Friends in each elderly school to recruit for the participants. Then, the investigaot will contact the participants and make an appointment. The number of participants suggested in qualitative studies is 4-10 participants for individual interviews. The number of participants will depend on the saturation of data to be agreed upon by the team.~Meanwhile, the participants for FGDs will be recruited based on inclusion criteria. The investigators will divide the two groups, namely the group of healthcare providers and elderly school managers. For the healthcare providers group, investigators will visit four Public Health Centers, then contact the nurses and managers in the elderly programs. Meanwhile, for the elderly school administrators, the investigators will contact them by WhatsApp chat group and make appointments. Each group consists of 4-12 participants.~Stage II (Quantitative study: Delphi methods modified) The sampling technique will use purposive sampling based on inclusion criteria. There are no standards regarding the sample size in Delphi studies. The sample size varies in many studies from 4 to 171 experts. A minimum of 20 experts will be recruited to this Delphi study. Experts will be invited to participate by the research team. They will be invited by email with a formal invitation to become a part of the panel.~Stage III (Quantitative study: Quasi experiment) The sampling technique will use purposive sampling. The sample count will be calculated based on previous studies, with the proportion of adverse events in the control group as 31.43% and the intervention group as 53.33%. Based on the proportions of previous studies, the researchers will calculate the number of samples needed. Researchers will use a sample calculator, Sample Size Version 2.0, from the World Health Organization (WHO) with Zα= 1,96 and Zβ = 0,84 and obtain 62 results for each group. In anticipation of the possibility of respondents dropping out, 10% of the sample number to 62 + 10% = 68 family members. Furthermore, the researchers will divide the control and intervention groups based on geographical locations so they are far apart from each other. The control group and the intervention will not be allowed to have communication. The control group is an elderly school in Ujung Berung and Cinambo sub-district, and the intervention group is in Central Antapani and Sukajadi sub-districts.~Data analysis Stage I (Qualitative) The investigators will analyze the data with content analysis guided by the total safety culture model. The investigators will read each transcript and then determine the coding. Coding will be done by AHS and discussed with the coauthor CE. Codes will be applied to raw data, and then grouped into categories to generate themes. Consensus concerning the codes and themes among at least three investigators (AHS, CE and PS) needs to be reached. Peer debriefing will be used to increase the credibility and the reliability of the data. Confirmability will be enhanced by keeping an audit trail of the documents.~Stage II (Quantitative study with Delphi method) Advance validity tests are conducted through readability tests by experts based on the ratings given by experts. In the first round of Delphi, the experts will be given a list of indicators that shape the dimensions of elderly safety culture at home. The investigators will provide the essential indicators that are developed for the model. Researchers will include a questionnaire to assess them by giving a score of 1-9. A score of 1-3 means it does not matter, 4-6 means less important, and 7-9 means very important. This scoring will be done individually where the researchers will meet the experts and explain the purpose of the study and provide a list of statements of indicators of elderly safety culture. The experts can revise or add to the indicator by filling in the response columns.~After obtaining the results of the first round Delphi, it will be continued with Delphi's second round. Items which do not achieve consensus in Round 1, with items that need to be revised and additional items will be discussed in Round 2.~The investigators will use median, minimum and maximum scores to analyze the data and will be reported to panel members as feedback after each round. The assessment of Delphi Round 1 and Round 2 will indicate if the item scored <7 it is considered not valid and > 7 the item is valid.~Stage III (Quantitative) Data analysis will be conducted with univariate, bivariate and multivariate analyses. The investigators will also perform normality and homogeneity tests before determining parametric or non-parametric statistical tests. Tests of normality and homogeneity are conducted to determine the equivalence between intervention and control groups. Homogeneity tests will be performed by the Levene test. When the p-value is more significant than alpha, the intervention and control groups can be inferred as equivalent or homogeneous. The normality test will use Kolmogorov Smirnov tests.~Data security All individual data will be kept in privacy and all members of team will be assured to data secrecy. The data collected from all work study will be anonymized and kept in accordance with the appropriate data protection guidelines.~Outcomes Stage I (Qualitative) The outcome of qualitative research will describe the themes about the safety in elderly related to the culture of safety in the elderly at home. The emerging themes will be adapted to the theory of Total Safety Culture which consists of three dimensions, including the personal, behavior and environmental dimensions.~Stage II (Quantitative) Based on the results of stage I, and the literature review, the investigators will formulate potential indicators to rate by the experts using the Delphi methods in stage II. The results of stage II, will be stated as indicators of elderly safety cultures. The list of indicators then will be organized into models.~Stage III (Quantitative study) The assessment of the culture of the safety of the elderly at home was developed from the results of a literature study on the instrumented assessment of safety culture. Based on the results of the study, there is no instrument that assesses the culture of elderly safety in the family, so we will make some modifications to the Nursing Home Survey of Patient Safety Culture (NHSOPSC) issued by AHRQ . The NHSOPSC consists of 42 questions plus two outcome questions, using answers in the form of Likert scales ranging from strongly agree, agree, neither agree or disagree, disagree, and strongly disagree. All items with positive statements are given a score of 5 (Strongly agree), 4 (agree), 3 (neither agree or disagree), 2 (disagree) and 1 (strongly disagree). Negative statements are scored as follows: If there is an answer they do not know, then it is considered missing (not answered) and will not be counted. Furthermore, the percentage score of 1-2 will be combined into a negative response, a score of 3 is neutral and a score of 4-5 is a positive response. Each dimension of the safety culture will be calculated on the average of the percentage of each item in that dimension and only calculated for a positive response.~Adverse events will be measured by the type and frequency (no events, 1-2 events, >3 events) experienced by the elderly at home before and after the model trial. Sociodemographic information will be collected in the baseline assessment, including age, sex, educational level, occupational, and relation with elderly.~Data management plans Interviews will be recorded, and all data will be transcribed verbatim and managed using Opencode software 4.03 version. Data in the Sundanese language will be translated into Bahasa Indonesian. Data will be entered into data collection sheets and confidentially stored in ongoing computer database. For quantitative data, th einvestigators will use SPSS release 22 (IBM Corp., Armonk, NY) administered by UGM. For qualitative study, the investigators will report the study by Consolidated Criteria for Reporting Qualitative Studies (COREQ) and the quantitative study will be reported by Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). For mixed methods study, the investigators will reported by Good Reporting of a Mixed Methods Study (GRAMMS) .~Ethical considerations Investigators will inform respondents either verbally and in writing about the objectives, methods, procedures and measurements during the study. They will also be informed about ethical issues such as confidentiality, their right to ask any questions during the study, and their right to withdraw at any time without consequence. To confirm that all respondents have received appropriate information about the study and have agreed to participate, all participants will be asked to sign a written consent form. This research will be conducted using the approval from the Medical and Health Research Ethics Committee of the Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada with the number KE/FK/0632/EC/2021.
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Development of the Ageing Safety From the Risk (ASRi) Model for Safety Culture by Empowering the Family at Home: a Mixed-methods Study Protocol
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Safety Issues
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* Other: Ageing Safe from the Risk (ASRi) Model of safety culture
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Inclusion Criteria:~Inclusion criteria for the elderly are: living with family; have a history of adverse events over the past one year such as falls, pressure ulcers, injuries, and problems due to treatment; can communicate effectively, and have a level of dependence: independent, mild, and moderate.~Inclusion criteria for family are: taking care of the elderly directly, can communicate effectively, and have a minimum age of 18 years.~Exclusion Criteria:~family did not continue the study, elderly were hospitalized, and died during the study.
|
18 Years
| null |
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: We will consist of two gorup. Control group and intervention group
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of safety culture | Rate of safety culture will be measured by instrument of safety culture that modified from the Nursing Home Patient Safety Culture and the results of Delphi at stage 2. | 16 weeks |
| Incidence of adverse events | Adverse events will be measured by the type and frequency (no events, 1-2 events, >3 events) experienced by the elderly at home before and after the model trial. | 16 weeks |
|
Safety culture, Elderly, Home care, Family, Indonesia
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention Group- Receiving intervention by educating, training and homevisit<br>For the intervention groups, planning will be done to provide education and training. Families will be given modules on Safety Culture in the Elderly and will also receive home visits to check and monitoring the condition of the elderly at home related to adverse events and the home environment. | Other: Ageing Safe from the Risk (ASRi) Model of safety culture<br>* For the intervention groups, planning will be done to provide education and training. Families will be given modules on Safety Culture in the Elderly. Materials provided about the safety of the elderly include changes in the elderly, the concept of safety in the elderly, the type of danger to the elderly, how to prevent harm in the elderly, the first handling in case of accidents, and the role of the family in the efforts of elderly safety. The material will be delivered by experts in elderly health and patient safety (professionals from health centers, social services, and academics). In addition to education and training, families will also receive home visits to check and monitoring the condition of the elderly at home related to adverse events and the home environment. Measuring will be done every 4 weeks by using a monitoring book.<br>|
| No Intervention: Control group<br>Thisi control group will only monitoring every 4 weeks by home visit. After 16 weeks, researchers will evaluate perceptions of the elderly's safety culture at home and adverse events at home | |
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Model for Safety Culture by Empowering the Family at Home: a Mixed-methods Study Protocol
Study Overview
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Brief Summary
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Background: The elderly are a vulnerable group for health problems as they age. Safe care is essential when caring for the elderly at home because adverse events can happen there, such as falls, pressure ulcers, injuries, or dangers caused by medication errors. Safety culture for the elderly at home needs to be developed so that they can avoid unexpected events. This study aimed to develop the model for safety culture among the elderly called Aging Safe from the Risk (ASRi) to improve the safety culture in elderly care at home. Methods: This exploratory sequential mixed methods study will consist of three stages. Stage 1, a qualitative descriptive study, will be conducted to explore the perceptions of families, nurses, and school administrators for the elderly regarding the safety of the elderly at home. Data will be collected by interviews and focus group discussions. Stage II will involve developing The ASRi model using the modified Delphi method. The list of elderly safety culture indicators will be assessed by experts and then further developed into a model. In stage III, a model test will be conducted with a non-equivalent control group using a quasi-experimental design. The investigators will provide interventions in the form of education and training to families regarding the safety culture for the elderly at home. Findings: There is a crucial need for studies assessing the safety culture in elderly care by empowering families at home to improve safety for the elderly. The results of this study will help fill the knowledge gap in this research and can aid in developing public health policy and programs for the elderly. .
Detailed Description
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This study aims to obtain a model of elderly safety culture by involving families in self-care at home to increase perceptions of safety culture and reduce adverse events at home. The specific aims are: Exploring the perceptions of families, healthcare providers, and elderly school administrators regarding the safety of the elderly at home; Develop the Ageing Safe from the Risk (ASRi) model of safety culture; and Conducting trials of applying the ASRi model to improve the perception of the elderly safety culture and reduce adverse events at home. This protocol have been approval from the Medical and Health Research Ethics Committee of the Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada-Dr. Sardjito General Hospital with the number KE/FK/0632/EC/2021 on the date in 10 June 2021. Study design This exploratory sequential mixed methods will include three stages, and the quantitative design will be the most dominant in this research. Setting This study will be conducted in Bandung, the capital city of West Java, Indonesia. Bandung has 30 subdistricts, and there are 4 subdistricts that have elderly schools. Elderly schools in Bandung have 275 members and are managed by Elderly Friends. The elderly school model was established in 2019 developed by Indonesia Ramah Lansia (IRL) West Java. Activities at the Bandung Elderly School include education about elderly health concerns and home visits by Elderly Friends to monitor the health of the elderly at home. Study stages and data collection Stage I (Qualitative Study) In the first stage, the descriptive exploratory will be used to explore the perceptions of families, the elderly, healthcare providers, and school administrators regarding the safety of the elderly at home. Data collection will be conducted with in-depth interviews with the elderly and families and focus group discussions (FGD) among the healthcare providers and elderly school managers In-depth interviews will be conducted to obtain complete information about perceptions of families and elderly about their safety, especially in four dimensions: the personal dimensions including family values/beliefs about the safety of the elderly, understanding, attitudes and family motivations towards the safety of the elderly; behavioral dimensions including communication patterns, cooperation, family stress and burden; and environmental dimensions including family efforts in creating a safe environment for the elderly. The interview guides (shown in Appendix 1) which contain open-ended questions and probes to explore the perceptions about safety in elderly care will be tested in pilot study. To increase credibility, researchers will use data triangulation by also observing the conditions of the elderly home. Furthermore, will also conduct interviews about the hopes and needs of families related to the safety of the elderly at home. Data collection also will be done among the elderly to obtain information about the experiences related to safety and security and their expectations regarding their safety at home. Interviews will be conducted face-to-face at participants' homes. Each in-depth interview and FGD will take between 60-90 minutes. In-depth interviews will be terminated when there is no additional information needed anymore (data saturation). In this pandemic period, the invesitagors will apply health protocols when conducting interviews, by using masks, maintaining safe distance, and ensuring the conditions of researchers and participants are in good health. The FGDs will be conducted in two groups: with healthcare providers and with administrators of elderly schools in four sub-district areas. FGDs will be held by the agreements of the participants, whether offline or online. Before the interviews, participants will provide their sociodemographic and related information such as age, education, occupation and race. Information about this research will be explained to all participants before they are required to sign an informed consent form. All interviews will be conducted in Indonesian or Sundanese language and audio-recorded. All data in Sundanese language will be translated into Indonesian. Stage 2 (Quantitative Study) In the second stage, the investigators will conduct Delphi methods with some modification (30) to find out indicator drafts that can be used to develop the ASRi Model. Modifications from the implementation of Delphi will be in stage 1 when researchers directly provide a list of indicators based on the results of the phase 1 study. In addition, in stage two the panel discussions will be conducted online or offline depending on the willingness of the experts. The Delphi methods modification will be done in two rounds. In the first round of Delphi, the investigators will compile a list of statement items that are indicators of the elderly safety culture at home based on the results of the first stage. Informed consent will be obtained from all participants at the first round. The investigators will contact the experts individually by phone or email to explain the purpose of research and implementation of Delphi. Then, the experts will be asked to provide an assessment of indicators in the safety culture of the elderly at home. The investigators will allocate two weeks for Delphi experts to respond in the first round. Reminders will be sent to participants one week before each round begins in order to maximize their participation. Then, we will process and refine the findings according to the assessment of the Delphi first round. Next, the Delphi second round will do by conducting expert panel discussions. The investigators will invite experts for discussions regarding the results of the first round of Delphi. Discussions will be conducted both online and offline (hybrid). All indicators resulting from the first round will be discussed in this expert panel. The results of the second round of Delphi will be developed into the ASRi model of safety culture in the elderly. Stage 3 (Quantitative Study) The third stage, testing the model will be done by conducting a quasi-experimental study with a non-equivalent control group using a pre-posttest design. The intervention Ageing Safe from the Risk (ASRi) will consist of about 16 weeks. First, the investigators will conduct training of trainers to nurses and elderly friends. They will be given modules. At this stage, the investigators will also prepare for the control groups and intervention groups. Selection of control and intervention groups based on geographical locations. Two research assistants, with minimum education of bachelor nursing, will conduct a survey for pre-test measurements and make home visits in each groups. Previously, the investigators will explain about filling out the questionnaire to the research assistants. For the intervention groups, planning will be done to provide education and training. Families will be given modules on Safety Culture in the Elderly. Materials provided about the safety of the elderly include changes in the elderly, the concept of safety in the elderly, the type of danger to the elderly, how to prevent harm in the elderly, the first handling in case of accidents, and the role of the family in the efforts of elderly safety. The material will be delivered by experts in elderly health and patient safety (professionals from health centers, social services, and academics). In addition to education and training, families will also receive home visits to check and monitoring the condition of the elderly at home related to adverse events and the home environment. Measuring will be done every 2 weeks by using a monitoring book. In the control groups, activities as usual will be carried out by the elderly friends. After 16 weeks, researchers will evaluate perceptions of the elderly's safety culture at home and adverse events at home. STUDY POPULATION Participants Stage I (Qualitative study) The qualitative study aims to explore the perceptions of family, elderly, healthcare providers, and administrators of elderly schools about safety in the elderly. This study will conduct individual interviews for family and the elderly, and FGD for healthcare providers and administrators of elderly schools. This study will include the elderly and their families who are members of the elderly schools in Bandung, healthcare providers from the Public Health Centers, and administrators of elderly schools in Bandung. The sampling technique will use purposive sampling and maximum variation. Inclusion criteria for elderly are: living with family; level of independence are independent, mild and moderate based on Barthel Index [31], no impaired cognitive function, and communication. Inclusion criteria for the family are: family members who live with the elderly and age at least 18 years old or more. Inclusion criteria for healthcare providers are: minimum education background of diploma with one year of work experience in caring for elderly. Inclusion criteria for elderly school administrators are: manager of The Indonesia Ramah Lansia (IRL) West Java who manages elderly schools in Bandung, and administrators of elderly schools and active in managing elderly schools. There are four elderly schools in Bandung, and each elderly school will involve two administrators. Stage II (Quantitative study with Delphi method) Purpose of study is to develop the Ageing Safe from the Risk (ASRi) model of safety culture. The subjects in this stage II study are experts in elderly nursing, family nursing, patient safety, and stakeholders related to elderly health programs. Criteria of experts in this study are: geriatric doctors with experience caring for elderly at home; healthcare providers in elderly programs; elderly school managers; managers of IRL West Java; lecturers in family nursing, gerontics and patient safety; families who have experience caring for the elderly, and stakeholders from social services and National Population and Family Planning Board. Stage III (Quantitative study) The purpose of the study is to test the ASRi model in improving perceptions of safety culture and decreasing adverse events in the elderly at home. At this stage of the study, the population is the elderly and family members of the Bandung City Elderly School in 2020. The sample in this study are the elderly and families who are members of elderly schools in Bandung. Purposive sampling will be used to recruit the samples. Inclusion criteria for the elderly are: living with family; have a history of adverse events over the past one year such as falls, pressure ulcers, injuries, and problems due to treatment; can communicate effectively, and have a level of dependence: independent, mild, and moderate. Inclusion criteria for family are: taking care of the elderly directly, can communicate effectively, and have a minimum age of 18 years. Withdrawal criteria: family did not continue the study, elderly were hospitalized, and died during the study. Sampling methods and sample size Stage I (Qualitative study) The sampling technique will use purposive sampling. The investigators (AHS) will recruit participants for individual interviewing in subdistrict Central Antapani, Sukajadi, Ujung Berung and Cinambo based on the inclusion criteria. First, investigators will contact the Elderly Friends in each elderly school to recruit for the participants. Then, the investigaot will contact the participants and make an appointment. The number of participants suggested in qualitative studies is 4-10 participants for individual interviews. The number of participants will depend on the saturation of data to be agreed upon by the team. Meanwhile, the participants for FGDs will be recruited based on inclusion criteria. The investigators will divide the two groups, namely the group of healthcare providers and elderly school managers. For the healthcare providers group, investigators will visit four Public Health Centers, then contact the nurses and managers in the elderly programs. Meanwhile, for the elderly school administrators, the investigators will contact them by WhatsApp chat group and make appointments. Each group consists of 4-12 participants. Stage II (Quantitative study: Delphi methods modified) The sampling technique will use purposive sampling based on inclusion criteria. There are no standards regarding the sample size in Delphi studies. The sample size varies in many studies from 4 to 171 experts. A minimum of 20 experts will be recruited to this Delphi study. Experts will be invited to participate by the research team. They will be invited by email with a formal invitation to become a part of the panel. Stage III (Quantitative study: Quasi experiment) The sampling technique will use purposive sampling. The sample count will be calculated based on previous studies, with the proportion of adverse events in the control group as 31.43% and the intervention group as 53.33%. Based on the proportions of previous studies, the researchers will calculate the number of samples needed. Researchers will use a sample calculator, Sample Size Version 2.0, from the World Health Organization (WHO) with Zα= 1,96 and Zβ = 0,84 and obtain 62 results for each group. In anticipation of the possibility of respondents dropping out, 10% of the sample number to 62 + 10% = 68 family members. Furthermore, the researchers will divide the control and intervention groups based on geographical locations so they are far apart from each other. The control group and the intervention will not be allowed to have communication. The control group is an elderly school in Ujung Berung and Cinambo sub-district, and the intervention group is in Central Antapani and Sukajadi sub-districts. Data analysis Stage I (Qualitative) The investigators will analyze the data with content analysis guided by the total safety culture model. The investigators will read each transcript and then determine the coding. Coding will be done by AHS and discussed with the coauthor CE. Codes will be applied to raw data, and then grouped into categories to generate themes. Consensus concerning the codes and themes among at least three investigators (AHS, CE and PS) needs to be reached. Peer debriefing will be used to increase the credibility and the reliability of the data. Confirmability will be enhanced by keeping an audit trail of the documents. Stage II (Quantitative study with Delphi method) Advance validity tests are conducted through readability tests by experts based on the ratings given by experts. In the first round of Delphi, the experts will be given a list of indicators that shape the dimensions of elderly safety culture at home. The investigators will provide the essential indicators that are developed for the model. Researchers will include a questionnaire to assess them by giving a score of 1-9. A score of 1-3 means it does not matter, 4-6 means less important, and 7-9 means very important. This scoring will be done individually where the researchers will meet the experts and explain the purpose of the study and provide a list of statements of indicators of elderly safety culture. The experts can revise or add to the indicator by filling in the response columns. After obtaining the results of the first round Delphi, it will be continued with Delphi's second round. Items which do not achieve consensus in Round 1, with items that need to be revised and additional items will be discussed in Round 2. The investigators will use median, minimum and maximum scores to analyze the data and will be reported to panel members as feedback after each round. The assessment of Delphi Round 1 and Round 2 will indicate if the item scored <7 it is considered not valid and > 7 the item is valid. Stage III (Quantitative) Data analysis will be conducted with univariate, bivariate and multivariate analyses. The investigators will also perform normality and homogeneity tests before determining parametric or non-parametric statistical tests. Tests of normality and homogeneity are conducted to determine the equivalence between intervention and control groups. Homogeneity tests will be performed by the Levene test. When the p-value is more significant than alpha, the intervention and control groups can be inferred as equivalent or homogeneous. The normality test will use Kolmogorov Smirnov tests. Data security All individual data will be kept in privacy and all members of team will be assured to data secrecy. The data collected from all work study will be anonymized and kept in accordance with the appropriate data protection guidelines. Outcomes Stage I (Qualitative) The outcome of qualitative research will describe the themes about the safety in elderly related to the culture of safety in the elderly at home. The emerging themes will be adapted to the theory of Total Safety Culture which consists of three dimensions, including the personal, behavior and environmental dimensions. Stage II (Quantitative) Based on the results of stage I, and the literature review, the investigators will formulate potential indicators to rate by the experts using the Delphi methods in stage II. The results of stage II, will be stated as indicators of elderly safety cultures. The list of indicators then will be organized into models. Stage III (Quantitative study) The assessment of the culture of the safety of the elderly at home was developed from the results of a literature study on the instrumented assessment of safety culture. Based on the results of the study, there is no instrument that assesses the culture of elderly safety in the family, so we will make some modifications to the Nursing Home Survey of Patient Safety Culture (NHSOPSC) issued by AHRQ . The NHSOPSC consists of 42 questions plus two outcome questions, using answers in the form of Likert scales ranging from strongly agree, agree, neither agree or disagree, disagree, and strongly disagree. All items with positive statements are given a score of 5 (Strongly agree), 4 (agree), 3 (neither agree or disagree), 2 (disagree) and 1 (strongly disagree). Negative statements are scored as follows: If there is an answer they do not know, then it is considered missing (not answered) and will not be counted. Furthermore, the percentage score of 1-2 will be combined into a negative response, a score of 3 is neutral and a score of 4-5 is a positive response. Each dimension of the safety culture will be calculated on the average of the percentage of each item in that dimension and only calculated for a positive response. Adverse events will be measured by the type and frequency (no events, 1-2 events, >3 events) experienced by the elderly at home before and after the model trial. Sociodemographic information will be collected in the baseline assessment, including age, sex, educational level, occupational, and relation with elderly. Data management plans Interviews will be recorded, and all data will be transcribed verbatim and managed using Opencode software 4.03 version. Data in the Sundanese language will be translated into Bahasa Indonesian. Data will be entered into data collection sheets and confidentially stored in ongoing computer database. For quantitative data, th einvestigators will use SPSS release 22 (IBM Corp., Armonk, NY) administered by UGM. For qualitative study, the investigators will report the study by Consolidated Criteria for Reporting Qualitative Studies (COREQ) and the quantitative study will be reported by Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). For mixed methods study, the investigators will reported by Good Reporting of a Mixed Methods Study (GRAMMS) . Ethical considerations Investigators will inform respondents either verbally and in writing about the objectives, methods, procedures and measurements during the study. They will also be informed about ethical issues such as confidentiality, their right to ask any questions during the study, and their right to withdraw at any time without consequence. To confirm that all respondents have received appropriate information about the study and have agreed to participate, all participants will be asked to sign a written consent form. This research will be conducted using the approval from the Medical and Health Research Ethics Committee of the Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada with the number KE/FK/0632/EC/2021.
Official Title
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Development of the Ageing Safety From the Risk (ASRi) Model for Safety Culture by Empowering the Family at Home: a Mixed-methods Study Protocol
Conditions
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Safety Issues
Intervention / Treatment
-----------------
* Other: Ageing Safe from the Risk (ASRi) Model of safety culture
Participation Criteria
=================
Eligibility Criteria
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Inclusion Criteria: Inclusion criteria for the elderly are: living with family; have a history of adverse events over the past one year such as falls, pressure ulcers, injuries, and problems due to treatment; can communicate effectively, and have a level of dependence: independent, mild, and moderate. Inclusion criteria for family are: taking care of the elderly directly, can communicate effectively, and have a minimum age of 18 years. Exclusion Criteria: family did not continue the study, elderly were hospitalized, and died during the study.
Ages Eligible for Study
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Minimum Age: 18 Years
Sexes Eligible for Study
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All
Accepts Healthy Volunteers
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Accepts Healthy Volunteers
Study Plan
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How is the study designed?
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Design Details
Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: We will consist of two gorup. Control group and intervention group
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention Group- Receiving intervention by educating, training and homevisit<br>For the intervention groups, planning will be done to provide education and training. Families will be given modules on Safety Culture in the Elderly and will also receive home visits to check and monitoring the condition of the elderly at home related to adverse events and the home environment. | Other: Ageing Safe from the Risk (ASRi) Model of safety culture<br>* For the intervention groups, planning will be done to provide education and training. Families will be given modules on Safety Culture in the Elderly. Materials provided about the safety of the elderly include changes in the elderly, the concept of safety in the elderly, the type of danger to the elderly, how to prevent harm in the elderly, the first handling in case of accidents, and the role of the family in the efforts of elderly safety. The material will be delivered by experts in elderly health and patient safety (professionals from health centers, social services, and academics). In addition to education and training, families will also receive home visits to check and monitoring the condition of the elderly at home related to adverse events and the home environment. Measuring will be done every 4 weeks by using a monitoring book.<br>|
| No Intervention: Control group<br>Thisi control group will only monitoring every 4 weeks by home visit. After 16 weeks, researchers will evaluate perceptions of the elderly's safety culture at home and adverse events at home | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of safety culture | Rate of safety culture will be measured by instrument of safety culture that modified from the Nursing Home Patient Safety Culture and the results of Delphi at stage 2. | 16 weeks |
| Incidence of adverse events | Adverse events will be measured by the type and frequency (no events, 1-2 events, >3 events) experienced by the elderly at home before and after the model trial. | 16 weeks |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Safety culture, Elderly, Home care, Family, Indonesia
|
||
NCT03313596
|
Multicenter RCT of ADV-TK Gene Therapy Improving the Outcome of Liver Transplantation for Advanced HCC
|
Compare the effect of liver transplantation (LT) plus ADV-TK gene therapy versus LT only in advanced primary hepatocellular carcinoma.
|
Multicenter Randomized Controlled Trial of Adenovirus-mediated Adjuvant Gene Therapy Improving Outcome of Liver Transplantation in Patients With Advanced Hepatocellular Carcinoma
|
Hepatocellular Carcinoma
|
* Drug: ADV-Tk
* Procedure: LT
|
Inclusion Criteria:~18 - 65 years of age (Male and Female).~Clinical diagnosis of advanced primary hepatocellular carcinoma who could accept liver transplantation.~Patients who had unresectable HCC with single tumor diameter > 5 cm and ≤ 10cm; or numbers of multiple tumors >3 and ≤ 5, and the total length of foci diameter ≤ 15 cm.~Serum AFP ≤ 10000 ng/ml before liver transplantation.~Child-pugh A-B.~No metastasis in extrahepatic main vescular and extrahepatic lymph node detected during the operation and no metastasis of other organs.~Provide written informed consent before screening.~Exclusion Criteria:~Metastasis in extrahepatic organs.~HCC with Invasion in extrahepatic main vescular and extrahepatic organs.~Contraindications of operation of other organ system.~Hypersensitivity to adenovirus, GCV or similar drugs.~Serious obstacle of the mechanism of coagulation, hemorrhagic tendency, and abnormal coagulation (≥50%).~Plan to accept clinical trials of other antitumor drugs.~Immunological deficit.~HBsAg(+) and HBcAb(+) donor.~Unsuitable participate assessed by investigator.
|
18 Years
|
65 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival, PFS | PFS was measured from the day of liver transplantation to objective recurrence (MRI or CT) or HCC-related death, whichever occurred first. | 2-year |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival, OS | OS was measured from the day of liver transplantation to death. | 1-year |
| Overall survival, OS | OS was measured from the day of liver transplantation to death. | 2-year |
| Time of the tumor progression,TTP | TTP was the median period from the day of liver transplantation to objective recurrence (MRI or CT). | 2-year |
| Median overall survival time | | 2-year |
|
Carcinoma, Carcinoma, Hepatocellular, Neoplasms, Glandular and Epithelial, Neoplasms by Histologic Type, Neoplasms, Adenocarcinoma, Liver Neoplasms, Digestive System Neoplasms, Neoplasms by Site, Digestive System Diseases, Liver Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: LT-only<br>patients received orthotopic LT and subsequent immunosuppression therapy | Procedure: LT<br>* Orthotopic LT and subsequent immunosuppression therapy<br>|
| Experimental: LT+ADV-TK<br>ADV-TK therapy was administered in addition to orthotopic LT and subsequent immunosuppression therapy | Drug: ADV-Tk<br>* The first ADV-TK dose was administered during the operation; 1.0×10(12) viral particles of ADV-TK in 100 mL of 0.9% saline were injected into peritoneum tissues around the liver. The second and third ADV-TK dose was administered 60 days and 90 days after LT; 1.0×10(12) viral particles of ADV-TK in 100 mL of 0.9% saline were injected into the celiac artery (60 mL) and the superior mesenteric artery (40 mL) via femoral-artery puncture.<br>Procedure: LT<br>* Orthotopic LT and subsequent immunosuppression therapy<br>|
|
Multicenter RCT of ADV-TK Gene Therapy Improving the Outcome of Liver Transplantation for Advanced HCC
Study Overview
=================
Brief Summary
-----------------
Compare the effect of liver transplantation (LT) plus ADV-TK gene therapy versus LT only in advanced primary hepatocellular carcinoma.
Official Title
-----------------
Multicenter Randomized Controlled Trial of Adenovirus-mediated Adjuvant Gene Therapy Improving Outcome of Liver Transplantation in Patients With Advanced Hepatocellular Carcinoma
Conditions
-----------------
Hepatocellular Carcinoma
Intervention / Treatment
-----------------
* Drug: ADV-Tk
* Procedure: LT
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18 - 65 years of age (Male and Female). Clinical diagnosis of advanced primary hepatocellular carcinoma who could accept liver transplantation. Patients who had unresectable HCC with single tumor diameter > 5 cm and ≤ 10cm; or numbers of multiple tumors >3 and ≤ 5, and the total length of foci diameter ≤ 15 cm. Serum AFP ≤ 10000 ng/ml before liver transplantation. Child-pugh A-B. No metastasis in extrahepatic main vescular and extrahepatic lymph node detected during the operation and no metastasis of other organs. Provide written informed consent before screening. Exclusion Criteria: Metastasis in extrahepatic organs. HCC with Invasion in extrahepatic main vescular and extrahepatic organs. Contraindications of operation of other organ system. Hypersensitivity to adenovirus, GCV or similar drugs. Serious obstacle of the mechanism of coagulation, hemorrhagic tendency, and abnormal coagulation (≥50%). Plan to accept clinical trials of other antitumor drugs. Immunological deficit. HBsAg(+) and HBcAb(+) donor. Unsuitable participate assessed by investigator.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: LT-only<br>patients received orthotopic LT and subsequent immunosuppression therapy | Procedure: LT<br>* Orthotopic LT and subsequent immunosuppression therapy<br>|
| Experimental: LT+ADV-TK<br>ADV-TK therapy was administered in addition to orthotopic LT and subsequent immunosuppression therapy | Drug: ADV-Tk<br>* The first ADV-TK dose was administered during the operation; 1.0×10(12) viral particles of ADV-TK in 100 mL of 0.9% saline were injected into peritoneum tissues around the liver. The second and third ADV-TK dose was administered 60 days and 90 days after LT; 1.0×10(12) viral particles of ADV-TK in 100 mL of 0.9% saline were injected into the celiac artery (60 mL) and the superior mesenteric artery (40 mL) via femoral-artery puncture.<br>Procedure: LT<br>* Orthotopic LT and subsequent immunosuppression therapy<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival, PFS | PFS was measured from the day of liver transplantation to objective recurrence (MRI or CT) or HCC-related death, whichever occurred first. | 2-year |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival, OS | OS was measured from the day of liver transplantation to death. | 1-year |
| Overall survival, OS | OS was measured from the day of liver transplantation to death. | 2-year |
| Time of the tumor progression,TTP | TTP was the median period from the day of liver transplantation to objective recurrence (MRI or CT). | 2-year |
| Median overall survival time | | 2-year |
|
||
NCT02336607
|
The Effects on Blood Pressure Control, Pulse Wave Velocity, as Well as Safety and Tolerability of Felodipine Sustained Release in Chinese Patients.
|
The purpose of this study is to evaluate the effects on blood pressure control, pulse wave velocity, as well as safety and tolerability of felodipine single or combine with other drugs in Chinese Hypertension patients.
|
In this study, investigators will choose male and female subjects aged between 35 and 79 years old with mild to moderate essential hypertension. At first 2 weeks, all patients will use felodipine 5mg daily. If the blood pressure dosen't meet the target (140/90mmHg), they will be randomized into metoprolol, lisinopril or hydrochlorothiazide combination groups for another 4 weeks therapy. After that, if the blood pressure has still not met the target, up-titrate the felodipine into 10mg, followed by a 4 weeks therapy. And if the blood pressure is still not met the target after that, up-titrate the combine drugs into maximum dosage. The whole treatment duration is 14 weeks.~The primary outcome is to evaluate the percentage of subjects reaching blood pressure target (defined as < 140 / 90 mmHg) after 14 weeks treatment with felodipine sustained release in combination with metoprolol, lisinopril or hydrochlorothiazide.
|
A Randomized, Open-label Study to Evaluate the Effects on Blood Pressure Control, Pulse Wave Velocity, as Well as Safety and Tolerability of Felodipine Sustained Release, Alone and in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide, in Chinese Patients With Mild to Moderate Essential Hypertension.
|
Hypertension
|
* Drug: Felodipine tablet (Plendil)+Hydrochlorothiazide
* Drug: Felodipine tablet (Plendil)+Metoprolol tablet (Betaloc ZOK)
* Drug: Felodipine tablets (Plendil)+Lisinopril (Zestril)
* Drug: Felodipine tablet (Plendil) alone
|
Inclusion Criteria:~Provision of written informed consent~Female or male aged between 35-79 years old~Mild to moderate essential hypertension patients who meet any of the following criterias:~Newly diagnosed, drug-naive, or without any antihypertension treatment for at least 3 months, moderate essential hypertension patients. (160mmHg mean SiSBP 180mmHg or 100mmHg mean SiDBP 110mmHg)~Newly diagnosed, drug-naive, or without any antihypertension treatment for at least 3 months, mild essential hypertension patients (140mmHg mean SiSBP 160mmHg or 90mmHg mean SiDBP 100mmHg) with high or extreme high cardiovascular risk (a)(having 3 or more than 3 risk factors and/or target organ lesion and/or diabetes mellitus).~(a) according to Chinese guideline for prevention and treatment of patients with hypertension 2004.~The patients have already received starting dosage of single anti-hypertension drug therapy (exclude the drugs containing felodipine component ), however the blood pressure is not well controlled (140mmHg mean SiSBP 160mmHg or 90mmHg mean SiDBP 100mmHg). After stopping the drug for 5 eliminating half life time, the patients meet any one of the following two:~160mmHg mean SiSBP 180mmHg or 100mmHg mean SiDBP 110mmHg.~140mmHg mean SiSBP 160mmHg or 90mmHg mean SiDBP 100mmHg) with high or extreme high cardiovascular risk* (having 3 or more than 3 risk factors and/or target organ lesion and/or diabetes mellitus).~Sitting blood pressure is taken after subjects take a seat to rest for 5 minutes before the next medication.~Exclusion Criteria:~Any of the following is regarded as a criterion for exclusion from the study:~Known or suspected secondary hypertension~Resting heart rate is < 55bpm.~Sick sinus syndrome~Atrioventricular block of first degree (with P-R>0.24seconds), or second or third degree~Other clinical significant arrhythmia~Unstable and/or decompensated congestive heart failure~Angina, acute myocardial infarction, percutaneous coronary intervention (PCI), or cardiac surgery~Asthma or moderate to severe chronic obstructive pulmonary disease~Type 1 diabetes mellitus~Gout history~Fasting serum glucose of greater than 200 mg/dl (11.1 mmol/L) or type 2 diabetes mellitus needs insulin therapy~ALT>3ULN~Cr>1.5mg/dl~Pregnancy or lactation.~Alcohol or drug abuse~Known need for other concomitant anti-hypertensive therapy during the study besides the study drug.~Known or suspected allergy to investigational drug or non-active ingredients of investigational drugs, known allergy to other blockers, calcium antagonist, diuretics, angiotensin converting enzyme inhibitor or with other contraindications.~Suspected white-coat hypertension based on investigator's judgement.
|
35 Years
|
79 Years
|
All
|
No
|
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Subjects Reaching Blood Pressure Target (Defined as < 140 / 90 mmHg) After 14 Weeks of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide. | | 14 weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Subjects Reaching Blood Pressure Target (Defined as < 140 / 90 mmHg) After 4 Weeks of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide. | The duration of the combination therapy was 4 weeks. Blood pressure was measured at week 6 of the trial. | 4 weeks |
| The Percentage of Subjects Reaching Blood Pressure Target (Defined as < 140 / 90 mmHg) After 8 Weeks of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide. | The duration of the combination therapy was 8 weeks. Blood pressure was measured at week 10 of the trial. | 8 weeks |
| The Magnitude of Systolic and Diastolic Blood Pressure Change From Baseline Among All Randomized Subjects After 4 Weeks of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide. | The duration of the combination therapy was 4 weeks. Blood pressure was measured at week 6 of the trial. | 4 weeks |
| The Magnitude of Systolic and Diastolic Blood Pressure Changes From Baseline Among All Randomized Subjects After 8 Weeks of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide. | The duration of the combination therapy was 8 weeks. Blood pressure was measured at week 10 of the trial. | 8 weeks |
| The Magnitude of Systolic and Diastolic Blood Pressure Changes From Baseline Among All Randomized Subjects After 12 Weeks of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide. | The duration of the combination therapy was 12 weeks. Blood pressure was measured at week 14 of the trial. | 12 weeks |
| The Magnitude of Systolic and Diastolic Blood Pressure Changes From Baseline Among the Subjects Who Reached Target at 4 Weeks of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide. | The duration of the combination therapy was 4 weeks. Blood pressure was measured at week 6 of the trial. | 4 weeks |
| The Magnitude of Systolic and Diastolic Blood Pressure Changes From Baseline Among the Subjects Who Reached Target After 8 Weeks of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide. | The duration of the combination therapy was 8 weeks. Blood pressure was measured at week 10 of the trial. | 8 weeks |
| The Magnitude of Systolic and Diastolic Blood Pressure Changes From Baseline Among the Subjects Who Reached Target at 12 Weeks of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide. | The duration of the combination therapy was 12 weeks. Blood pressure was measured at week 14 of the trial. | 12 weeks |
| The Change of Pulse Wave Velocity at 12 Weeks Compare With Baseline Data of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide. | The duration of the combination therapy was 12 weeks. The change of pulse wave velocity was measured at week 14 of the trial. | 12 weeks |
| The Change of Pulse Wave Velocity From Baseline at 2, 14 Weeks of Felodipine Sustained Release Alone. | The duration of the combination therapy was 12 weeks. The change of pulse wave velocity was measured at week 14 of the trial. | 12 weeks |
| The Magnitude of Systolic and Diastolic Blood Pressure Changes From Baseline Among the Subjects Who Reached Target at 2 Weeks of Felodipine Sustained Release, Alone | The duration of the combination therapy was 2 weeks. Blood pressure was measured at week 2 of the trial. | 2 weeks |
|
Metoprolol, Felodipine, Hydrochlorothiazide, Lisinopril, Antihypertensive Agents, Diuretics, Natriuretic Agents, Physiological Effects of Drugs, Sodium Chloride Symporter Inhibitors, Membrane Transport Modulators, Molecular Mechanisms of Pharmacological Action, Anti-Arrhythmia Agents, Peripheral Nervous System Agents, Adrenergic beta-1 Receptor Antagonists, Adrenergic beta-Antagonists, Adrenergic Antagonists, Adrenergic Agents, Neurotransmitter Agents, Angiotensin-Converting Enzyme Inhibitors, Protease Inhibitors, Enzyme Inhibitors, Cardiotonic Agents, Protective Agents, Calcium Channel Blockers, Calcium-Regulating Hormones and Agents, Vasodilator Agents, Sympatholytics, Autonomic Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Felodipine tablet (Plendil)<br> | Drug: Felodipine tablet (Plendil) alone<br>* Felodipine sustained release tablet single drug therapy (1st week- 2nd week) Eligible subjects will first take felodipine tablet 5mg, once daily, orally for 2 weeks. If blood pressure is controlled after 2 weeks, then the subjects will continue the treatment until the end of primary therapy stage (14th week).<br>|
| Active Comparator: Felodipine tablet (Plendil)+Metoprolol tablet (Betaloc ZOK)<br> | Drug: Felodipine tablet (Plendil)+Metoprolol tablet (Betaloc ZOK)<br>* Step 1: Eligible subjects will first take felodipine tablet 5mg, once daily, orally for 2 weeks.~If blood pressure is not controlled after 2 weeks, then the subjects will go to Step 2: Felodipine sustained release tablet 5mg once daily combined with metoprolol succinate prolonged-release tablet (Betaloc ZOK) 47.5mg , once daily. If blood pressure is not controlled after 4 weeks, then the subjects will go to Step 3: The dosage of felodipine sustained release tablet will be escalated to 10mg, once daily, while the dosage of the combined drug remains the same. If blood pressure is not controlled after 4 weeks, then the subjects will go to Step 4: The dosage of felodipine sustained release tablet keeps 10mg, once daily, while the dosage of different combined drug is doubled.<br>|
| Active Comparator: Felodipine tablets (Plendil)+Lisinopril (Zestril)<br> | Drug: Felodipine tablets (Plendil)+Lisinopril (Zestril)<br>* Step 1: Eligible subjects will first take felodipine tablet 5mg, once daily, orally for 2 weeks.~If blood pressure is not controlled after 2 weeks, then the subjects will go to Step 2: Felodipine sustained release tablet 5mg once daily combined with Lisinopril (Zestril) 10mg, once daily. If blood pressure is not controlled after 4 weeks, then the subjects will go to Step 3: The dosage of felodipine sustained release tablet will be escalated to 10mg, once daily, while the dosage of the combined drug remains the same. If blood pressure is not controlled after 4 weeks, then the subjects will go to Step 4: The dosage of felodipine sustained release tablet keeps 10mg, once daily, while the dosage of different combined drug is doubled.<br>|
| Active Comparator: Felodipine tablet (Plendil)+Hydrochlorothiazide<br> | Drug: Felodipine tablet (Plendil)+Hydrochlorothiazide<br>* Step 1: Eligible subjects will first take felodipine tablet 5mg, once daily, orally for 2 weeks.~If blood pressure is not controlled after 2 weeks, then the subjects will go to Step 2: Felodipine sustained release tablet 5mg once daily combined with hydrochlorothiazide 12.5mg, once daily. If blood pressure is not controlled after 4 weeks, then the subjects will go to Step 3: The dosage of felodipine sustained release tablet will be escalated to 10mg, once daily, while the dosage of the combined drug remains the same. If blood pressure is not controlled after 4 weeks, then the subjects will go to Step 4: The dosage of felodipine sustained release tablet keeps 10mg, once daily, while the dosage of different combined drug is doubled.<br>|
|
The Effects on Blood Pressure Control, Pulse Wave Velocity, as Well as Safety and Tolerability of Felodipine Sustained Release in Chinese Patients.
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the effects on blood pressure control, pulse wave velocity, as well as safety and tolerability of felodipine single or combine with other drugs in Chinese Hypertension patients.
Detailed Description
-----------------
In this study, investigators will choose male and female subjects aged between 35 and 79 years old with mild to moderate essential hypertension. At first 2 weeks, all patients will use felodipine 5mg daily. If the blood pressure dosen't meet the target (140/90mmHg), they will be randomized into metoprolol, lisinopril or hydrochlorothiazide combination groups for another 4 weeks therapy. After that, if the blood pressure has still not met the target, up-titrate the felodipine into 10mg, followed by a 4 weeks therapy. And if the blood pressure is still not met the target after that, up-titrate the combine drugs into maximum dosage. The whole treatment duration is 14 weeks. The primary outcome is to evaluate the percentage of subjects reaching blood pressure target (defined as < 140 / 90 mmHg) after 14 weeks treatment with felodipine sustained release in combination with metoprolol, lisinopril or hydrochlorothiazide.
Official Title
-----------------
A Randomized, Open-label Study to Evaluate the Effects on Blood Pressure Control, Pulse Wave Velocity, as Well as Safety and Tolerability of Felodipine Sustained Release, Alone and in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide, in Chinese Patients With Mild to Moderate Essential Hypertension.
Conditions
-----------------
Hypertension
Intervention / Treatment
-----------------
* Drug: Felodipine tablet (Plendil)+Hydrochlorothiazide
* Drug: Felodipine tablet (Plendil)+Metoprolol tablet (Betaloc ZOK)
* Drug: Felodipine tablets (Plendil)+Lisinopril (Zestril)
* Drug: Felodipine tablet (Plendil) alone
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Provision of written informed consent Female or male aged between 35-79 years old Mild to moderate essential hypertension patients who meet any of the following criterias: Newly diagnosed, drug-naive, or without any antihypertension treatment for at least 3 months, moderate essential hypertension patients. (160mmHg mean SiSBP 180mmHg or 100mmHg mean SiDBP 110mmHg) Newly diagnosed, drug-naive, or without any antihypertension treatment for at least 3 months, mild essential hypertension patients (140mmHg mean SiSBP 160mmHg or 90mmHg mean SiDBP 100mmHg) with high or extreme high cardiovascular risk (a)(having 3 or more than 3 risk factors and/or target organ lesion and/or diabetes mellitus). (a) according to Chinese guideline for prevention and treatment of patients with hypertension 2004. The patients have already received starting dosage of single anti-hypertension drug therapy (exclude the drugs containing felodipine component ), however the blood pressure is not well controlled (140mmHg mean SiSBP 160mmHg or 90mmHg mean SiDBP 100mmHg). After stopping the drug for 5 eliminating half life time, the patients meet any one of the following two: 160mmHg mean SiSBP 180mmHg or 100mmHg mean SiDBP 110mmHg. 140mmHg mean SiSBP 160mmHg or 90mmHg mean SiDBP 100mmHg) with high or extreme high cardiovascular risk* (having 3 or more than 3 risk factors and/or target organ lesion and/or diabetes mellitus). Sitting blood pressure is taken after subjects take a seat to rest for 5 minutes before the next medication. Exclusion Criteria: Any of the following is regarded as a criterion for exclusion from the study: Known or suspected secondary hypertension Resting heart rate is < 55bpm. Sick sinus syndrome Atrioventricular block of first degree (with P-R>0.24seconds), or second or third degree Other clinical significant arrhythmia Unstable and/or decompensated congestive heart failure Angina, acute myocardial infarction, percutaneous coronary intervention (PCI), or cardiac surgery Asthma or moderate to severe chronic obstructive pulmonary disease Type 1 diabetes mellitus Gout history Fasting serum glucose of greater than 200 mg/dl (11.1 mmol/L) or type 2 diabetes mellitus needs insulin therapy ALT>3ULN Cr>1.5mg/dl Pregnancy or lactation. Alcohol or drug abuse Known need for other concomitant anti-hypertensive therapy during the study besides the study drug. Known or suspected allergy to investigational drug or non-active ingredients of investigational drugs, known allergy to other blockers, calcium antagonist, diuretics, angiotensin converting enzyme inhibitor or with other contraindications. Suspected white-coat hypertension based on investigator's judgement.
Ages Eligible for Study
-----------------
Minimum Age: 35 Years
Maximum Age: 79 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Felodipine tablet (Plendil)<br> | Drug: Felodipine tablet (Plendil) alone<br>* Felodipine sustained release tablet single drug therapy (1st week- 2nd week) Eligible subjects will first take felodipine tablet 5mg, once daily, orally for 2 weeks. If blood pressure is controlled after 2 weeks, then the subjects will continue the treatment until the end of primary therapy stage (14th week).<br>|
| Active Comparator: Felodipine tablet (Plendil)+Metoprolol tablet (Betaloc ZOK)<br> | Drug: Felodipine tablet (Plendil)+Metoprolol tablet (Betaloc ZOK)<br>* Step 1: Eligible subjects will first take felodipine tablet 5mg, once daily, orally for 2 weeks. If blood pressure is not controlled after 2 weeks, then the subjects will go to Step 2: Felodipine sustained release tablet 5mg once daily combined with metoprolol succinate prolonged-release tablet (Betaloc ZOK) 47.5mg , once daily. If blood pressure is not controlled after 4 weeks, then the subjects will go to Step 3: The dosage of felodipine sustained release tablet will be escalated to 10mg, once daily, while the dosage of the combined drug remains the same. If blood pressure is not controlled after 4 weeks, then the subjects will go to Step 4: The dosage of felodipine sustained release tablet keeps 10mg, once daily, while the dosage of different combined drug is doubled.<br>|
| Active Comparator: Felodipine tablets (Plendil)+Lisinopril (Zestril)<br> | Drug: Felodipine tablets (Plendil)+Lisinopril (Zestril)<br>* Step 1: Eligible subjects will first take felodipine tablet 5mg, once daily, orally for 2 weeks. If blood pressure is not controlled after 2 weeks, then the subjects will go to Step 2: Felodipine sustained release tablet 5mg once daily combined with Lisinopril (Zestril) 10mg, once daily. If blood pressure is not controlled after 4 weeks, then the subjects will go to Step 3: The dosage of felodipine sustained release tablet will be escalated to 10mg, once daily, while the dosage of the combined drug remains the same. If blood pressure is not controlled after 4 weeks, then the subjects will go to Step 4: The dosage of felodipine sustained release tablet keeps 10mg, once daily, while the dosage of different combined drug is doubled.<br>|
| Active Comparator: Felodipine tablet (Plendil)+Hydrochlorothiazide<br> | Drug: Felodipine tablet (Plendil)+Hydrochlorothiazide<br>* Step 1: Eligible subjects will first take felodipine tablet 5mg, once daily, orally for 2 weeks. If blood pressure is not controlled after 2 weeks, then the subjects will go to Step 2: Felodipine sustained release tablet 5mg once daily combined with hydrochlorothiazide 12.5mg, once daily. If blood pressure is not controlled after 4 weeks, then the subjects will go to Step 3: The dosage of felodipine sustained release tablet will be escalated to 10mg, once daily, while the dosage of the combined drug remains the same. If blood pressure is not controlled after 4 weeks, then the subjects will go to Step 4: The dosage of felodipine sustained release tablet keeps 10mg, once daily, while the dosage of different combined drug is doubled.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Subjects Reaching Blood Pressure Target (Defined as < 140 / 90 mmHg) After 14 Weeks of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide. | | 14 weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Subjects Reaching Blood Pressure Target (Defined as < 140 / 90 mmHg) After 4 Weeks of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide. | The duration of the combination therapy was 4 weeks. Blood pressure was measured at week 6 of the trial. | 4 weeks |
| The Percentage of Subjects Reaching Blood Pressure Target (Defined as < 140 / 90 mmHg) After 8 Weeks of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide. | The duration of the combination therapy was 8 weeks. Blood pressure was measured at week 10 of the trial. | 8 weeks |
| The Magnitude of Systolic and Diastolic Blood Pressure Change From Baseline Among All Randomized Subjects After 4 Weeks of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide. | The duration of the combination therapy was 4 weeks. Blood pressure was measured at week 6 of the trial. | 4 weeks |
| The Magnitude of Systolic and Diastolic Blood Pressure Changes From Baseline Among All Randomized Subjects After 8 Weeks of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide. | The duration of the combination therapy was 8 weeks. Blood pressure was measured at week 10 of the trial. | 8 weeks |
| The Magnitude of Systolic and Diastolic Blood Pressure Changes From Baseline Among All Randomized Subjects After 12 Weeks of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide. | The duration of the combination therapy was 12 weeks. Blood pressure was measured at week 14 of the trial. | 12 weeks |
| The Magnitude of Systolic and Diastolic Blood Pressure Changes From Baseline Among the Subjects Who Reached Target at 4 Weeks of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide. | The duration of the combination therapy was 4 weeks. Blood pressure was measured at week 6 of the trial. | 4 weeks |
| The Magnitude of Systolic and Diastolic Blood Pressure Changes From Baseline Among the Subjects Who Reached Target After 8 Weeks of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide. | The duration of the combination therapy was 8 weeks. Blood pressure was measured at week 10 of the trial. | 8 weeks |
| The Magnitude of Systolic and Diastolic Blood Pressure Changes From Baseline Among the Subjects Who Reached Target at 12 Weeks of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide. | The duration of the combination therapy was 12 weeks. Blood pressure was measured at week 14 of the trial. | 12 weeks |
| The Change of Pulse Wave Velocity at 12 Weeks Compare With Baseline Data of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide. | The duration of the combination therapy was 12 weeks. The change of pulse wave velocity was measured at week 14 of the trial. | 12 weeks |
| The Change of Pulse Wave Velocity From Baseline at 2, 14 Weeks of Felodipine Sustained Release Alone. | The duration of the combination therapy was 12 weeks. The change of pulse wave velocity was measured at week 14 of the trial. | 12 weeks |
| The Magnitude of Systolic and Diastolic Blood Pressure Changes From Baseline Among the Subjects Who Reached Target at 2 Weeks of Felodipine Sustained Release, Alone | The duration of the combination therapy was 2 weeks. Blood pressure was measured at week 2 of the trial. | 2 weeks |
|
|
NCT02565342
|
Interscalene Brachial Plexus Block to Treat Pain After Clavicular Surgery
|
The sensory innervation of the clavicle remains an area of debate. Regional nerve blocks aimed at relieving pre- and post-operative pain include the superficial cervical plexus blocks, interscalene blocks and a combined version of the above. In this case study, the investigators aim to describe the protocol used in a university hospital: general anaesthesia with interscalene brachial plexus block, followed by optional iv morphine administration in phase 1 recovery and oral oxycodone on the ward.
|
Interscalene Brachial Plexus Block to Treat Pain After Clavicular Surgery
|
Acute Pain
|
* Procedure: Interscalene brachial plexus block
|
Inclusion Criteria:~clavicular fracture with internal reduction~physical status I - III~Exclusion Criteria:~contraindication to regional anaesthesia~history of neck radiotherapy~patient suffering from chronic pain~severe respiratory disease
|
18 Years
|
70 Years
|
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IV Morphine consumption in phase 1 recovery (mg) | morphine administered in postanaesthetic care unit by nursers if pains score > 3/10, per protocol | 0-2 hours after surgery |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain scores at rest and on movement (numeric rating scale, 0-10) | | Postoperative day 0 and 1 |
| Postoperative nausea and vomiting (yes/no) | | Postoperative day 0 and 1 |
| Itching (yes/no) | | Postoperative day 0 and 1 |
| Cumulative oxycodone consumption (mg) | | up to postoperative day 1 |
|
Clavicle
|
Acute Pain, Pain, Neurologic Manifestations
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Interscalene brachial plexus block<br> | Procedure: Interscalene brachial plexus block<br> <br> |
|
Interscalene Brachial Plexus Block to Treat Pain After Clavicular Surgery
Study Overview
=================
Brief Summary
-----------------
The sensory innervation of the clavicle remains an area of debate. Regional nerve blocks aimed at relieving pre- and post-operative pain include the superficial cervical plexus blocks, interscalene blocks and a combined version of the above. In this case study, the investigators aim to describe the protocol used in a university hospital: general anaesthesia with interscalene brachial plexus block, followed by optional iv morphine administration in phase 1 recovery and oral oxycodone on the ward.
Official Title
-----------------
Interscalene Brachial Plexus Block to Treat Pain After Clavicular Surgery
Conditions
-----------------
Acute Pain
Intervention / Treatment
-----------------
* Procedure: Interscalene brachial plexus block
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: clavicular fracture with internal reduction physical status I - III Exclusion Criteria: contraindication to regional anaesthesia history of neck radiotherapy patient suffering from chronic pain severe respiratory disease
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Interscalene brachial plexus block<br> | Procedure: Interscalene brachial plexus block<br> <br> |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IV Morphine consumption in phase 1 recovery (mg) | morphine administered in postanaesthetic care unit by nursers if pains score > 3/10, per protocol | 0-2 hours after surgery |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain scores at rest and on movement (numeric rating scale, 0-10) | | Postoperative day 0 and 1 |
| Postoperative nausea and vomiting (yes/no) | | Postoperative day 0 and 1 |
| Itching (yes/no) | | Postoperative day 0 and 1 |
| Cumulative oxycodone consumption (mg) | | up to postoperative day 1 |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Clavicle
|
|
NCT01322750
|
Circulating Tumor Cells (CTCs): A Potential Screening Test for Clinically Undetectable Breast Carcinoma
|
With an estimated > 2 million women with undetected breast cancer in the United States, the need for improved early detection is imperative. Early diagnosis for these women is key to minimizing quality life-years lost to disease and optimizing success of treatment. Evidence now exists supporting the finding that systemic spread is an early event in the natural history of breast cancer, manifested as a release of single cancer cells from the incident, clinically undetectable tumor, which circulate through the bloodstream and deposit within remote tissues. Reliable and accurate detection of these circulating tumor cells (CTCs) is now possible with a simple peripheral venous blood draw. This study hypothesizes that women with CTCs and no other signs of malignancy have clinically undetectable disease.~This study will attempt to validate this technology as a breast cancer screening test and acquire data to determine the clinical validity and utility of this proposed screening methodology on a relatively young, ethnically diverse population who are eligible military health care beneficiaries. Furthermore, this study will attempt to bank identified CTCs in order to perform additional molecular analyses in the future. The specific aims are to develop a simple, reliable, cost-effective, and clinically relevant breast cancer screening test in order to identify subclinical disease early in its natural history in subjects at risk of progression to clinically apparent disease over the ensuing decade. The ultimate goal is to decrease the treatment-related morbidity and cause-specific mortality of breast cancer. An experienced team devoted to the care of patients with breast disease has been assembled to achieve this goal.
|
Circulating Tumor Cells (CTCs): A Potential Screening Test for Clinically Undetectable Breast Carcinoma
|
Breast Abnormality
|
Inclusion Criteria:~Adults 18 years of age or older~Mentally competent and willing to provide written informed consent prior to entering the study~Military healthcare beneficiary~Undergoing a diagnostic or therapeutic procedure (biopsy, lumpectomy, mastectomy) in the breast clinic or operating room.~Present to the CBCP and willing to be followed at the CBCP during the course of treatment and follow-up~Exclusion Criteria:~Prior history of invasive carcinoma~Presence of clinically-apparent metastatic disease~Participants with known human immunodeficiency virus (HIV), any history of hepatitis, prion-mediated disease, drug resistant tuberculosis or other infectious disease presenting a significant risk to personnel handling tissue or blood-derived products shall be excluded from participation~Participants with pre-existing coagulopathies or all other conditions, for whom invasive biopsy or surgery is medically contraindicated
|
18 Years
| null |
All
|
Accepts Healthy Volunteers
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
|
Breast Neoplasms, Neoplastic Cells, Circulating, Neoplasms, Neoplasms by Site, Breast Diseases, Skin Diseases, Neoplasm Metastasis, Neoplastic Processes, Pathologic Processes
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| With CTCs<br>Those individuals whom are identified with CTCs | |
| Without CTCs<br>Those individuals whom present and did not have CTCs | |
|
Circulating Tumor Cells (CTCs): A Potential Screening Test for Clinically Undetectable Breast Carcinoma
Study Overview
=================
Brief Summary
-----------------
With an estimated > 2 million women with undetected breast cancer in the United States, the need for improved early detection is imperative. Early diagnosis for these women is key to minimizing quality life-years lost to disease and optimizing success of treatment. Evidence now exists supporting the finding that systemic spread is an early event in the natural history of breast cancer, manifested as a release of single cancer cells from the incident, clinically undetectable tumor, which circulate through the bloodstream and deposit within remote tissues. Reliable and accurate detection of these circulating tumor cells (CTCs) is now possible with a simple peripheral venous blood draw. This study hypothesizes that women with CTCs and no other signs of malignancy have clinically undetectable disease. This study will attempt to validate this technology as a breast cancer screening test and acquire data to determine the clinical validity and utility of this proposed screening methodology on a relatively young, ethnically diverse population who are eligible military health care beneficiaries. Furthermore, this study will attempt to bank identified CTCs in order to perform additional molecular analyses in the future. The specific aims are to develop a simple, reliable, cost-effective, and clinically relevant breast cancer screening test in order to identify subclinical disease early in its natural history in subjects at risk of progression to clinically apparent disease over the ensuing decade. The ultimate goal is to decrease the treatment-related morbidity and cause-specific mortality of breast cancer. An experienced team devoted to the care of patients with breast disease has been assembled to achieve this goal.
Official Title
-----------------
Circulating Tumor Cells (CTCs): A Potential Screening Test for Clinically Undetectable Breast Carcinoma
Conditions
-----------------
Breast Abnormality
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults 18 years of age or older Mentally competent and willing to provide written informed consent prior to entering the study Military healthcare beneficiary Undergoing a diagnostic or therapeutic procedure (biopsy, lumpectomy, mastectomy) in the breast clinic or operating room. Present to the CBCP and willing to be followed at the CBCP during the course of treatment and follow-up Exclusion Criteria: Prior history of invasive carcinoma Presence of clinically-apparent metastatic disease Participants with known human immunodeficiency virus (HIV), any history of hepatitis, prion-mediated disease, drug resistant tuberculosis or other infectious disease presenting a significant risk to personnel handling tissue or blood-derived products shall be excluded from participation Participants with pre-existing coagulopathies or all other conditions, for whom invasive biopsy or surgery is medically contraindicated
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| With CTCs<br>Those individuals whom are identified with CTCs | |
| Without CTCs<br>Those individuals whom present and did not have CTCs | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
|
|||||
NCT01633060
|
A Phase III Study of BKM120 With Fulvestrant in Patients With HR+,HER2-, AI Treated, Locally Advanced or Metastatic Breast Cancer Who Progressed on or After mTORi
|
This study was a multicenter, randomized, double-blind, placebo-controlled Phase III study to determine the efficacy and safety of treatment with Buparlisib plus Fulvestrant vs. Placebo plus Fulvestrant in postmenopausal women with hormone Receptor-positive (HR-positive), human epidermal growth factor receptor 2-negative (HER2-negative), aromatase inhibitor (AI)-treated, locally advanced or metastatic breast cancer whose disease progressed on or after mammalian target of rapamycin inhibitor (mTORi)-based treatment.~Patients were randomized in 2:1 ratio to treatment with buparlisib 100 mg daily in combination with fulvestrant 500 mg or placebo daily in combination with fulvestrant 500 mg. Randomization was stratified according to visceral disease status (present or absent).
|
Novartis decided not to pursue further development of buparlisib program. On 19 Dec 2016, Novartis notified the Investigators about this decision; accordingly the CBKM120F2303 study was terminated.
|
A Phase III Randomized, Double Blind, Placebo Controlled Study of BKM120 With Fulvestrant, in Postmenopausal Women With Hormone Receptor-positive HER2-negative AI Treated, Locally Advanced or Metastatic Breast Cancer Who Progressed on or After mTOR Inhibitor Based Treatment
|
Metastatic Breast Cancer
|
* Drug: Fulvestrant
* Drug: BKM120
* Drug: BKM120 matching placebo
|
Key inclusion criteria~Female patients age 18 years or older~Histologically and/or cytologically confirmed diagnosis of breast cancer~Radiologic evidence of inoperable locally advanced or metastatic breast cancer~Adequate tumor tissue for the analysis of PI3K-related biomarkers~Human epidermal growth factor receptor-2 (HER2) negative disease, and a known positive hormone receptor status~Postmenopausal women~Prior treatment with aromatase inhibitors~Evidence of progression to the combination of mTORi and endocrine therapy given as the last therapy prior to study entry~Adequate bone marrow and organ function~ECOG performance status ≤ 2~Key exclusion criteria~Previous treatment with PI3K inhibitors, protein kinase B inhibitors or fulvestrant~More than one chemotherapy line for metastatic disease~Hypersensitivity to any of the excipients of buparlisib or fulvestrant~Symptomatic central nervous system metastases~Concurrent malignancy or malignancy within 3 years of study enrollment~Certain drugs or radiation within 2-4 weeks of enrollment~Increasing or chronic treatment (>5 days) with corticosteroids or another immunosuppressive agent~Certain scores on an anxiety and depression mood questionnaire given at screening~Acute viral hepatitis or a history of chronic or active hepatitis B virus or hepatitis C virus~Active cardiac disease or a history of cardiac dysfunction
|
18 Years
| null |
Female
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) Based on Local Investigator Assessment - Full Analysis Set (FAS) | Progression Free Survival (PFS) is defined as the time from date of randomization to the date of first radiologically documented progression or death due to any cause. If a patient did not progress or die at the time of the analysis data cut-off or start of new antineoplastic therapy, PFS was censored at the date of the last adequate tumor assessment before the earliest of the cut-off date or the start date of additional anti-neoplastic therapy. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria RECIST v1.1, as 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline and/or unequivocal progression of the non-target lesions and/or appearance of a new lesion. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm. Patients were followed up for approximately every 6 weeks after randomization. | Every 6 weeks after randomization up to a maximum of 4 years |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) - Full Analysis Set (FAS) | Overall Survival (OS) is defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died by the date of analysis cut-off, OS was censored at the date of last known date patient alive. Patients were followed up approximately every 6 weeks after randomization and every 3 months during survival follow-up. | Every 6 weeks after randomization up to a maximum of 5 years |
| Progression Free Survival (PFS) by PIK3CA Mutational Status | Progression Free Survival (PFS) is defined as the time from date of randomization to the date of first radiologically documented progression or death due to any cause. If a patient did not progress or die at the time of the analysis data cut-off or start of new antineoplastic therapy, PFS was censored at the date of the last adequate tumor assessment before the earliest of the cut-off date or the start date of additional anti-neoplastic therapy. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria RECIST v1.1, as 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline and/or unequivocal progression of the non-target lesions and/or appearance of a new lesion. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm. Patients were followed up for approximately every 6 weeks after randomization. | Every 6 weeks after randomization up to a maximum of 5 years |
| Overall Survival (OS) by PIK3CA Mutational Status | Overall Survival (OS) by PIK3CA mutational status based on ctDNA is defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died by the date of analysis cut-off, OS was censored at the date of last known date patient alive. Patients were followed up approximately every 6 weeks after randomization and every 3 months during survival follow-up. | Every 6 weeks after randomization up to a maximum of 5 years |
| Overall Response Rate (ORR) by PIK3CA Mutational Status | Overall Response Rate (ORR) is defined as the proportion of participants with best overall response of complete response (CR) or partial response (PR) based on local investigator's assessment according to RECIST 1.1. ORR was analyzed in the full population and by PIK3CA mutational status based on ctDNA. Response Evaluation Criteria in Solid Tumors (RECIST v1.1) for target/non target lesions: Complete Response (CR), disappearance of all target/non target lesions (all lymph nodes assigned as non-target lesions must be non-pathological in size (< 10 mm short axis)); Partial response (PR), >=30% decrease in the sum of the longest diameter of target lesions ; Overall Response (OR)= CR+PR. Patients were followed up for the duration of the study and for approximately every 6 weeks after randomization. | Every 6 weeks after randomization up to a maximum of 5 years |
| Clinical Benefit Rate (CBR) by PIK3CA Mutational Status | Clinical Benefit Rate (CBR) is defined as the proportion of participants with a best overall response of complete response (CR) or partial response (PR) or stable disease (SD) or Non-CR/non-PD lasting more than 14 or 24 weeks based on local investigator's assessment according to RECIST 1.1. CBR was analyzed in the full population and by PIK3CA mutational status based on ctDNA. Patients were followed up for the duration of the study and approximately every 6 weeks after randomization. | Week 14, Week 24 |
| Long-term Safety and Tolerability in the Two Treatment Arms - Safety Set (SS) | Analysis of frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths. | From first dose of study treatment to 30 days after last dose of study treatment, up to 5 years |
| Plasma Concentration-time Profiles of BKM120 in Combination With Fulvestrant at Cycle 1 Day 1 - Pharmacokinetic Analysis Set (PAS) | Plasma samples were collected from the first 100 BKM120-treated patients on Cycle 1 Day 1 (at 1h, 2h, and 6h post-dose and a recommended 9h post-dose sample). | C1D1 1 hour post dose, C1D1 2 hour post dose, C1D1 6 hour post dose and C1D1 9 hour post dose |
| Predose Trough Concentration-time Profile of BKM120 in Combination With Fulvestrant Over Time - Pharmacokinetic Analysis Set (PAS) | Pre-dose samples were collected for trough concentrations at Cycle 1 Day 15, Cycle 2 Day 1, Cycle 3 Day 1 and Cycle 4 Day 1. | C1D15, C2D1, C3D1 and C4D1 |
| Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Global Health Status/Quality of Life Per EORTC-QLQ-C30 - Full Analysis Set (FAS) | The global health status/QoL scale score of the QLQ-C30 is identified as the primary PRO variable of interest. Physical Functioning (PF), Emotional Functioning (EF) and Social Functioning (SF) scale scores of the QLQ-C30. The time to definitive 10% deterioration is defined as the time from the randomization date to the date of an event, which is defined as a worsening (decrease) in score by at least 10% compared to baseline, with no later increase above this threshold observed during the course of the study or death due to any cause. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. A high score for a functional scale represents a high /healthy level of functioning, a high score for the global health status / QoL represents a high QoL. | Baseline, Week 6 (C2D15), Week 12 (C4D1), then every 8 weeks until discontinuation (a cycle [C] = 4 weeks) up to 5 years. |
| Time to Definitive Deterioration of ECOG Performance Status From Baseline - Full Analysis Set (FAS) | The Eastern Cooperative Oncology Group (ECOG) Performance Status is a scale used to assess how a patient's disease is progressing, assess how the disease affects the daily living abilities of the patient, and determine appropriate treatment and prognosis. The ECOG Performance Scores has 5 grades: 0 = fully active, able to carry on all pre-disease performance without restriction, 1 = restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work, 2 = ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours, 3 = capable of only limited self-care, confined to bed or chair more than 50% of waking hours, 4 = completely disabled, cannot carry on any self-care, totally confined to bed or chair and 5 = dead. Definitive deterioration is defined as no improvement in the ECOG status following observation of the deterioration. | Screening, Baseline (Cycle 1 Day 1) and then at day 1 of each cycle and at the EOT visit |
|
BKM120, fulvestrant, breast cancer, metastatic, locally advanced, AI treated, mTOR inhibitor, PI3K, PIK3CA, PTEN, HER2-, HR+
|
Estrogen Receptor Antagonists, Estrogen Antagonists, Hormone Antagonists, Hormones, Hormone Substitutes, and Hormone Antagonists, Physiological Effects of Drugs, Fulvestrant, Antineoplastic Agents, Hormonal, Antineoplastic Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BKM120 100mg + Fulvestrant<br>BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol. | Drug: Fulvestrant<br>* Intramuscular fulvestrant 500 mg (Day 1 and Day 15 of Cycle 1 and Day 1 of every cycle thereafter)<br>Drug: BKM120<br>* BKM120 100 mg once daily<br>|
| Placebo Comparator: Placebo + Fulvestrant<br>BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol. | Drug: Fulvestrant<br>* Intramuscular fulvestrant 500 mg (Day 1 and Day 15 of Cycle 1 and Day 1 of every cycle thereafter)<br>Drug: BKM120 matching placebo<br>* BKM120 matching placebo, once daily<br>|
|
A Phase III Study of BKM120 With Fulvestrant in Patients With HR+,HER2-, AI Treated, Locally Advanced or Metastatic Breast Cancer Who Progressed on or After mTORi
Study Overview
=================
Brief Summary
-----------------
This study was a multicenter, randomized, double-blind, placebo-controlled Phase III study to determine the efficacy and safety of treatment with Buparlisib plus Fulvestrant vs. Placebo plus Fulvestrant in postmenopausal women with hormone Receptor-positive (HR-positive), human epidermal growth factor receptor 2-negative (HER2-negative), aromatase inhibitor (AI)-treated, locally advanced or metastatic breast cancer whose disease progressed on or after mammalian target of rapamycin inhibitor (mTORi)-based treatment. Patients were randomized in 2:1 ratio to treatment with buparlisib 100 mg daily in combination with fulvestrant 500 mg or placebo daily in combination with fulvestrant 500 mg. Randomization was stratified according to visceral disease status (present or absent).
Detailed Description
-----------------
Novartis decided not to pursue further development of buparlisib program. On 19 Dec 2016, Novartis notified the Investigators about this decision; accordingly the CBKM120F2303 study was terminated.
Official Title
-----------------
A Phase III Randomized, Double Blind, Placebo Controlled Study of BKM120 With Fulvestrant, in Postmenopausal Women With Hormone Receptor-positive HER2-negative AI Treated, Locally Advanced or Metastatic Breast Cancer Who Progressed on or After mTOR Inhibitor Based Treatment
Conditions
-----------------
Metastatic Breast Cancer
Intervention / Treatment
-----------------
* Drug: Fulvestrant
* Drug: BKM120
* Drug: BKM120 matching placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Key inclusion criteria Female patients age 18 years or older Histologically and/or cytologically confirmed diagnosis of breast cancer Radiologic evidence of inoperable locally advanced or metastatic breast cancer Adequate tumor tissue for the analysis of PI3K-related biomarkers Human epidermal growth factor receptor-2 (HER2) negative disease, and a known positive hormone receptor status Postmenopausal women Prior treatment with aromatase inhibitors Evidence of progression to the combination of mTORi and endocrine therapy given as the last therapy prior to study entry Adequate bone marrow and organ function ECOG performance status ≤ 2 Key exclusion criteria Previous treatment with PI3K inhibitors, protein kinase B inhibitors or fulvestrant More than one chemotherapy line for metastatic disease Hypersensitivity to any of the excipients of buparlisib or fulvestrant Symptomatic central nervous system metastases Concurrent malignancy or malignancy within 3 years of study enrollment Certain drugs or radiation within 2-4 weeks of enrollment Increasing or chronic treatment (>5 days) with corticosteroids or another immunosuppressive agent Certain scores on an anxiety and depression mood questionnaire given at screening Acute viral hepatitis or a history of chronic or active hepatitis B virus or hepatitis C virus Active cardiac disease or a history of cardiac dysfunction
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
Female
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BKM120 100mg + Fulvestrant<br>BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol. | Drug: Fulvestrant<br>* Intramuscular fulvestrant 500 mg (Day 1 and Day 15 of Cycle 1 and Day 1 of every cycle thereafter)<br>Drug: BKM120<br>* BKM120 100 mg once daily<br>|
| Placebo Comparator: Placebo + Fulvestrant<br>BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol. | Drug: Fulvestrant<br>* Intramuscular fulvestrant 500 mg (Day 1 and Day 15 of Cycle 1 and Day 1 of every cycle thereafter)<br>Drug: BKM120 matching placebo<br>* BKM120 matching placebo, once daily<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) Based on Local Investigator Assessment - Full Analysis Set (FAS) | Progression Free Survival (PFS) is defined as the time from date of randomization to the date of first radiologically documented progression or death due to any cause. If a patient did not progress or die at the time of the analysis data cut-off or start of new antineoplastic therapy, PFS was censored at the date of the last adequate tumor assessment before the earliest of the cut-off date or the start date of additional anti-neoplastic therapy. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria RECIST v1.1, as 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline and/or unequivocal progression of the non-target lesions and/or appearance of a new lesion. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm. Patients were followed up for approximately every 6 weeks after randomization. | Every 6 weeks after randomization up to a maximum of 4 years |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) - Full Analysis Set (FAS) | Overall Survival (OS) is defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died by the date of analysis cut-off, OS was censored at the date of last known date patient alive. Patients were followed up approximately every 6 weeks after randomization and every 3 months during survival follow-up. | Every 6 weeks after randomization up to a maximum of 5 years |
| Progression Free Survival (PFS) by PIK3CA Mutational Status | Progression Free Survival (PFS) is defined as the time from date of randomization to the date of first radiologically documented progression or death due to any cause. If a patient did not progress or die at the time of the analysis data cut-off or start of new antineoplastic therapy, PFS was censored at the date of the last adequate tumor assessment before the earliest of the cut-off date or the start date of additional anti-neoplastic therapy. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria RECIST v1.1, as 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline and/or unequivocal progression of the non-target lesions and/or appearance of a new lesion. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm. Patients were followed up for approximately every 6 weeks after randomization. | Every 6 weeks after randomization up to a maximum of 5 years |
| Overall Survival (OS) by PIK3CA Mutational Status | Overall Survival (OS) by PIK3CA mutational status based on ctDNA is defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died by the date of analysis cut-off, OS was censored at the date of last known date patient alive. Patients were followed up approximately every 6 weeks after randomization and every 3 months during survival follow-up. | Every 6 weeks after randomization up to a maximum of 5 years |
| Overall Response Rate (ORR) by PIK3CA Mutational Status | Overall Response Rate (ORR) is defined as the proportion of participants with best overall response of complete response (CR) or partial response (PR) based on local investigator's assessment according to RECIST 1.1. ORR was analyzed in the full population and by PIK3CA mutational status based on ctDNA. Response Evaluation Criteria in Solid Tumors (RECIST v1.1) for target/non target lesions: Complete Response (CR), disappearance of all target/non target lesions (all lymph nodes assigned as non-target lesions must be non-pathological in size (< 10 mm short axis)); Partial response (PR), >=30% decrease in the sum of the longest diameter of target lesions ; Overall Response (OR)= CR+PR. Patients were followed up for the duration of the study and for approximately every 6 weeks after randomization. | Every 6 weeks after randomization up to a maximum of 5 years |
| Clinical Benefit Rate (CBR) by PIK3CA Mutational Status | Clinical Benefit Rate (CBR) is defined as the proportion of participants with a best overall response of complete response (CR) or partial response (PR) or stable disease (SD) or Non-CR/non-PD lasting more than 14 or 24 weeks based on local investigator's assessment according to RECIST 1.1. CBR was analyzed in the full population and by PIK3CA mutational status based on ctDNA. Patients were followed up for the duration of the study and approximately every 6 weeks after randomization. | Week 14, Week 24 |
| Long-term Safety and Tolerability in the Two Treatment Arms - Safety Set (SS) | Analysis of frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths. | From first dose of study treatment to 30 days after last dose of study treatment, up to 5 years |
| Plasma Concentration-time Profiles of BKM120 in Combination With Fulvestrant at Cycle 1 Day 1 - Pharmacokinetic Analysis Set (PAS) | Plasma samples were collected from the first 100 BKM120-treated patients on Cycle 1 Day 1 (at 1h, 2h, and 6h post-dose and a recommended 9h post-dose sample). | C1D1 1 hour post dose, C1D1 2 hour post dose, C1D1 6 hour post dose and C1D1 9 hour post dose |
| Predose Trough Concentration-time Profile of BKM120 in Combination With Fulvestrant Over Time - Pharmacokinetic Analysis Set (PAS) | Pre-dose samples were collected for trough concentrations at Cycle 1 Day 15, Cycle 2 Day 1, Cycle 3 Day 1 and Cycle 4 Day 1. | C1D15, C2D1, C3D1 and C4D1 |
| Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Global Health Status/Quality of Life Per EORTC-QLQ-C30 - Full Analysis Set (FAS) | The global health status/QoL scale score of the QLQ-C30 is identified as the primary PRO variable of interest. Physical Functioning (PF), Emotional Functioning (EF) and Social Functioning (SF) scale scores of the QLQ-C30. The time to definitive 10% deterioration is defined as the time from the randomization date to the date of an event, which is defined as a worsening (decrease) in score by at least 10% compared to baseline, with no later increase above this threshold observed during the course of the study or death due to any cause. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. A high score for a functional scale represents a high /healthy level of functioning, a high score for the global health status / QoL represents a high QoL. | Baseline, Week 6 (C2D15), Week 12 (C4D1), then every 8 weeks until discontinuation (a cycle [C] = 4 weeks) up to 5 years. |
| Time to Definitive Deterioration of ECOG Performance Status From Baseline - Full Analysis Set (FAS) | The Eastern Cooperative Oncology Group (ECOG) Performance Status is a scale used to assess how a patient's disease is progressing, assess how the disease affects the daily living abilities of the patient, and determine appropriate treatment and prognosis. The ECOG Performance Scores has 5 grades: 0 = fully active, able to carry on all pre-disease performance without restriction, 1 = restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work, 2 = ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours, 3 = capable of only limited self-care, confined to bed or chair more than 50% of waking hours, 4 = completely disabled, cannot carry on any self-care, totally confined to bed or chair and 5 = dead. Definitive deterioration is defined as no improvement in the ECOG status following observation of the deterioration. | Screening, Baseline (Cycle 1 Day 1) and then at day 1 of each cycle and at the EOT visit |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
BKM120, fulvestrant, breast cancer, metastatic, locally advanced, AI treated, mTOR inhibitor, PI3K, PIK3CA, PTEN, HER2-, HR+
|
NCT00167700
|
Pre-, Peri- and Postnatal Programming and Origins of Disease: Early Targeting the Epidemics of Allergy and Overweight
|
Combined programme: Nutrition, Allergy, Mucosal immunology and Intestinal microbiota (NAMI) was created with the objective to reverse the rising trend of chronic inflammatory diseases, such as allergic disease and obesity, by control of the internal and external environments of the infant. To approach this problem, the project aims to characterize~how immunology is regulated during pregnancy and early infancy,~how the immune interaction between mother and child is influenced by nutritional and microbial factors, and~how the regulation is related to disease risk.
|
While allergic diseases comprise the most common chronic disease in childhood, obesity is the most prevalent nutritional disorder among children throughout the world. In Europe, an estimated 20% of children and adolescents are overweight with one-third of these being considered obese. Moreover, escalation of these problems is expected in the future, since the velocity of propagation is highest in children. Although genetic factors can determine the propensity of an individual to become allergic or obese, these unlikely explain the recent and progressive worldwide increases in incidence. Rather, it would appear that the environmental changes more directly shape the risk during a critical period of life when the scene is set for the consolidation of the immune responder type. Prenatal environmental exposures may alter gene expression via epigenetic mechanisms, heritable changes in gene expression occurring without alterations in the DNA sequences.~Specifically current research interest is directed towards health promotion and reducing the risk of disease evaluating the probiotic effects with specific foods and nutrients, and assessing their interactions in optimal combination and food matrix. For this purpose a series of interventions studies evaluate the both the optimal timing of probiotic intervention and the optimal mode of administration.~Sections:~Prenatal~RCT 2 Randomized, parallel-design clinical trial of 3 groups. Pregnant women (n=256) from families with at least one member having an allergic disease have been recruited from maternal welfare clinics and randomly assigned to control group or one of the intervention groups. Mothers in the dietary intervention groups received dietary counselling with specific attention to the quality and quantity of fat in the diet. To promote the achievement of current dietary recommendations, mothers have been provided with foods which have a favourable fat composition (e.g. spreads). The subjects in the intervention groups have been further randomized (double-blind randomization) to receive either placebo or a probiotic preparation, 1010 cfu of both Lactobacillus rhamnosus GG and Bifidobacterium lactis and controls received placebo in a single-blind manner. Dietary food products and probiotic supplementation have been continued from the 1st trimester of pregnancy until the end of exclusive breast feeding, maximum of 6 months.~Perinatal~RCT 1 Randomized double-blind, placebo-controlled study of 2 groups. Pregnant women (n=159) have been randomized into one of the study groups 2-4 weeks before term to receive placebo (microcrystalline cellulose) or probiotic Lactobacillus rhamnosus GG (ATCC 53103; 1010 cfu). After delivery probiotics/ placebo were administered orally to the infants for 6 months. General information to prevent allergy has been given in written form to all: to breast-feed for at least 4-6 months; to begin solid foods at 4-6 months; no smoking by caretakers.~RCT 3 Randomized double-blind, placebo-controlled clinical trial of 3 groups. Pregnant women (n=241) with a history of atopic diseases have been assigned to one of the treatment groups: to receive for 2 months before delivery and for 2 months thereafter, when they are breast-feeding, either placebo or Lactobacillus rhamnosus and Bifidobacterium longum or Lactobacillus paracasei and Bifidobacterium longum.~Postnatal~RCT 4 Randomized double-blind, placebo-controlled study of 3 groups. Neonates (n=94) fulfilling the following criteria: gestational age at birth between 32nd and 36th weeks, weight over 1500 g and no congenital defects of gastrointestinal system or other defects that prevent enteral nutrition, have been randomized to receive either placebo (microcrystalline cellulose) or a probiotic preparation (Lactobacillus rhamnosus GG, ATCC 53103) or a prebiotic preparation (a mixture of Polydextrose and Galacto-oligosaccharideOS in a 1:1 ratio). The treatment continues for 2 months.~RCT 5 Randomized double-blind, placebo-controlled clinical trial of 2 groups. 2-6 weeks old formula- and breast-fed colic infants (n=30), who cry without medical cause for 3h/d, for 3days/week, have been randomized to receive either placebo (microcrystalline cellulose) or a probiotic preparation (Lactobacillus rhamnosus GG, ATCC 53103) for 4 weeks. Formula-fed infants receive extensively hydrolysed formula and mothers of breast-fed infants avoid cow's milk in their diet.
|
Nutrition, Allergy, Mucosal Immunology and Intestinal Microbiota (NAMI): Pre-, Peri- and Postnatal Programming and Origins of Disease: Early Targeting the Epidemics of Allergy and Overweight
|
Allergic Disease, Obesity, Immunology
|
* Behavioral: Dietary counselling and placebo
* Behavioral: Dietary counselling and probiotics
* Dietary Supplement: Placebo capsules
* Dietary Supplement: Probiotics
* Dietary Supplement: Prebiotics
|
Inclusion Criteria:~Pregnant women from families with at least one family member having an allergic disease~Exclusion Criteria:~Women presenting severe immunological or other chronic diseases (rheumatoid arthritis, diabetes, inflammatory bowel disease, thyroid diseases, malignancies etc.)~Women who cannot be expected to comply with treatment~Women currently participating or having participated in other clinical trial during the last 2 months prior to the beginning of the intervention.
|
18 Years
| null |
Female
|
No
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with allergic disease | | Up to 13 years |
| Weight gain | | Up to 13 years |
| Number of patients with chronic inflammatory disease | | Up to 13 years |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Innate immune gene expression patterns | | Up to 13 years |
| Microbiota composition | Amount of bacterial cells (per gram of faeces of mothers and infants as well as of breast milk) is measured using multiple methods, i.e. pyrosequencing, HIT-CHIP, qPCR, FISH and DGGE. | |
| Plasma glucose | | Up to 13 years |
| Cytokines in peripheral blood | | Up to 13 years |
| Cytokine profile in breast milk | | Up to 13 years |
| Cytokine profile in peripheral blood mononuclear cells (PBMC) | | Up to 13 years |
| GHbA1c | | Up to 13 years |
| Fatty acids | | Up to 13 years |
| Lipoproteins | | Up to 13 years |
| Intakes of foods and nutrients | | Up to 13 years |
| Blood pressure | | Up to 13 years |
| Leukotrienes in peripheral blood | | Up to 13 years |
| Adipokines | | Up to 13 years |
| Amount of crying in minutes | Crying minutes per day | Up to 1 year |
| Number of patients with functional gastrointestinal disorders | | Up to 13 years |
| Incidence of viral infections | | Up to 13 years |
|
atopic disease, probiotics, gut microbiota, allergy, nutrition, growth, allergic rhinitis, atopic sensitization, risk-markers of life-style related diseases
|
Overweight, Hypersensitivity, Overnutrition, Nutrition Disorders, Body Weight, Immune System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotics<br> | Dietary Supplement: Probiotics<br> <br> |
| Experimental: Probiotics + Dietary counseling<br> | Behavioral: Dietary counselling and probiotics<br>* Counseling to conform with the dietary recommendations. Food products commercially available including spreads and salad dressing. Probiotics<br>|
| Experimental: Dietary counseling + placebo<br> | Behavioral: Dietary counselling and placebo<br>* Counseling to conform with the dietary recommendations. Food products commercially available including spreads and salad dressing. Placebo capsules.<br>|
| Experimental: Prebiotics<br> | Dietary Supplement: Prebiotics<br> <br> |
| Placebo Comparator: Placebo<br> | Dietary Supplement: Placebo capsules<br>* Placebo capsules<br>|
| No Intervention: Control<br> | |
|
Pre-, Peri- and Postnatal Programming and Origins of Disease: Early Targeting the Epidemics of Allergy and Overweight
Study Overview
=================
Brief Summary
-----------------
Combined programme: Nutrition, Allergy, Mucosal immunology and Intestinal microbiota (NAMI) was created with the objective to reverse the rising trend of chronic inflammatory diseases, such as allergic disease and obesity, by control of the internal and external environments of the infant. To approach this problem, the project aims to characterize how immunology is regulated during pregnancy and early infancy, how the immune interaction between mother and child is influenced by nutritional and microbial factors, and how the regulation is related to disease risk.
Detailed Description
-----------------
While allergic diseases comprise the most common chronic disease in childhood, obesity is the most prevalent nutritional disorder among children throughout the world. In Europe, an estimated 20% of children and adolescents are overweight with one-third of these being considered obese. Moreover, escalation of these problems is expected in the future, since the velocity of propagation is highest in children. Although genetic factors can determine the propensity of an individual to become allergic or obese, these unlikely explain the recent and progressive worldwide increases in incidence. Rather, it would appear that the environmental changes more directly shape the risk during a critical period of life when the scene is set for the consolidation of the immune responder type. Prenatal environmental exposures may alter gene expression via epigenetic mechanisms, heritable changes in gene expression occurring without alterations in the DNA sequences. Specifically current research interest is directed towards health promotion and reducing the risk of disease evaluating the probiotic effects with specific foods and nutrients, and assessing their interactions in optimal combination and food matrix. For this purpose a series of interventions studies evaluate the both the optimal timing of probiotic intervention and the optimal mode of administration. Sections: Prenatal RCT 2 Randomized, parallel-design clinical trial of 3 groups. Pregnant women (n=256) from families with at least one member having an allergic disease have been recruited from maternal welfare clinics and randomly assigned to control group or one of the intervention groups. Mothers in the dietary intervention groups received dietary counselling with specific attention to the quality and quantity of fat in the diet. To promote the achievement of current dietary recommendations, mothers have been provided with foods which have a favourable fat composition (e.g. spreads). The subjects in the intervention groups have been further randomized (double-blind randomization) to receive either placebo or a probiotic preparation, 1010 cfu of both Lactobacillus rhamnosus GG and Bifidobacterium lactis and controls received placebo in a single-blind manner. Dietary food products and probiotic supplementation have been continued from the 1st trimester of pregnancy until the end of exclusive breast feeding, maximum of 6 months. Perinatal RCT 1 Randomized double-blind, placebo-controlled study of 2 groups. Pregnant women (n=159) have been randomized into one of the study groups 2-4 weeks before term to receive placebo (microcrystalline cellulose) or probiotic Lactobacillus rhamnosus GG (ATCC 53103; 1010 cfu). After delivery probiotics/ placebo were administered orally to the infants for 6 months. General information to prevent allergy has been given in written form to all: to breast-feed for at least 4-6 months; to begin solid foods at 4-6 months; no smoking by caretakers. RCT 3 Randomized double-blind, placebo-controlled clinical trial of 3 groups. Pregnant women (n=241) with a history of atopic diseases have been assigned to one of the treatment groups: to receive for 2 months before delivery and for 2 months thereafter, when they are breast-feeding, either placebo or Lactobacillus rhamnosus and Bifidobacterium longum or Lactobacillus paracasei and Bifidobacterium longum. Postnatal RCT 4 Randomized double-blind, placebo-controlled study of 3 groups. Neonates (n=94) fulfilling the following criteria: gestational age at birth between 32nd and 36th weeks, weight over 1500 g and no congenital defects of gastrointestinal system or other defects that prevent enteral nutrition, have been randomized to receive either placebo (microcrystalline cellulose) or a probiotic preparation (Lactobacillus rhamnosus GG, ATCC 53103) or a prebiotic preparation (a mixture of Polydextrose and Galacto-oligosaccharideOS in a 1:1 ratio). The treatment continues for 2 months. RCT 5 Randomized double-blind, placebo-controlled clinical trial of 2 groups. 2-6 weeks old formula- and breast-fed colic infants (n=30), who cry without medical cause for 3h/d, for 3days/week, have been randomized to receive either placebo (microcrystalline cellulose) or a probiotic preparation (Lactobacillus rhamnosus GG, ATCC 53103) for 4 weeks. Formula-fed infants receive extensively hydrolysed formula and mothers of breast-fed infants avoid cow's milk in their diet.
Official Title
-----------------
Nutrition, Allergy, Mucosal Immunology and Intestinal Microbiota (NAMI): Pre-, Peri- and Postnatal Programming and Origins of Disease: Early Targeting the Epidemics of Allergy and Overweight
Conditions
-----------------
Allergic Disease, Obesity, Immunology
Intervention / Treatment
-----------------
* Behavioral: Dietary counselling and placebo
* Behavioral: Dietary counselling and probiotics
* Dietary Supplement: Placebo capsules
* Dietary Supplement: Probiotics
* Dietary Supplement: Prebiotics
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Pregnant women from families with at least one family member having an allergic disease Exclusion Criteria: Women presenting severe immunological or other chronic diseases (rheumatoid arthritis, diabetes, inflammatory bowel disease, thyroid diseases, malignancies etc.) Women who cannot be expected to comply with treatment Women currently participating or having participated in other clinical trial during the last 2 months prior to the beginning of the intervention.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
Female
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotics<br> | Dietary Supplement: Probiotics<br> <br> |
| Experimental: Probiotics + Dietary counseling<br> | Behavioral: Dietary counselling and probiotics<br>* Counseling to conform with the dietary recommendations. Food products commercially available including spreads and salad dressing. Probiotics<br>|
| Experimental: Dietary counseling + placebo<br> | Behavioral: Dietary counselling and placebo<br>* Counseling to conform with the dietary recommendations. Food products commercially available including spreads and salad dressing. Placebo capsules.<br>|
| Experimental: Prebiotics<br> | Dietary Supplement: Prebiotics<br> <br> |
| Placebo Comparator: Placebo<br> | Dietary Supplement: Placebo capsules<br>* Placebo capsules<br>|
| No Intervention: Control<br> | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with allergic disease | | Up to 13 years |
| Weight gain | | Up to 13 years |
| Number of patients with chronic inflammatory disease | | Up to 13 years |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Innate immune gene expression patterns | | Up to 13 years |
| Microbiota composition | Amount of bacterial cells (per gram of faeces of mothers and infants as well as of breast milk) is measured using multiple methods, i.e. pyrosequencing, HIT-CHIP, qPCR, FISH and DGGE. | |
| Plasma glucose | | Up to 13 years |
| Cytokines in peripheral blood | | Up to 13 years |
| Cytokine profile in breast milk | | Up to 13 years |
| Cytokine profile in peripheral blood mononuclear cells (PBMC) | | Up to 13 years |
| GHbA1c | | Up to 13 years |
| Fatty acids | | Up to 13 years |
| Lipoproteins | | Up to 13 years |
| Intakes of foods and nutrients | | Up to 13 years |
| Blood pressure | | Up to 13 years |
| Leukotrienes in peripheral blood | | Up to 13 years |
| Adipokines | | Up to 13 years |
| Amount of crying in minutes | Crying minutes per day | Up to 1 year |
| Number of patients with functional gastrointestinal disorders | | Up to 13 years |
| Incidence of viral infections | | Up to 13 years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
atopic disease, probiotics, gut microbiota, allergy, nutrition, growth, allergic rhinitis, atopic sensitization, risk-markers of life-style related diseases
|
NCT04991350
|
Effect of Ranibizumab Versus Bevacizumab on the Macular Perfusion in Diabetic Macular Edema
|
The Early Treatment Diabetic Retinopathy Study (ETDRS) group founded guidelines for treating patients with clinically significant diabetic macular edema (DME) with focal/grid macular laser photocoagulation. Since then, macular laser, and steroids, were the main therapies for the treatment of DME until anti-vascular endothelial growth factors (anti-VEGF) drugs were developed after a growing body of scientific evidence implicated VEGF in the pathophysiologic process of DME.~Anti-VEGF drugs have been implicated in the treatment of DME. VEGF has been shown to play an important role in the occurrence of increased vascular permeability in DME. VEGF levels are significantly higher in patients with DME and extensive leakage than in patients with minimal leakage.~Many studies such as Diabetic Retinopathy Clinical Research [DRCR] Network studies, RESTORE Study, RISE and RIDE Research Group, and The BOLT Study have supported the use of anti-VEGF agents in the treatment of DME with better visual outcomes using anti-VEGF injections alone or in combination with other treatments.~Several ocular complications of intravitreal anti-VEGF injections have been reported including endophthalmitis, cataract, and retinal detachment. The different effects on macular perfusion between different anti-VEGFs have yet to be fully concluded with mixed conclusions that it increases or decreases or has no effect on perfusion of the macula in response to Anti-VEGF treatment. In many of these studies, however, patients with more ischemic retinas were not included. Retinal ischemia is a vital factor determining the diabetic retinopathy progression and prognosis.~Optical coherence tomography angiography (OCTA) detects blood flow by analyzing signal decorrelation between two sequential OCT cross-sectional scans at the same location. As it detects the movements of red blood corpuscles within the vessels, compared to the stationary retinal surroundings, which will result in signal disparity and imaging The split-spectrum amplitude-decorrelation angiography (SSADA) algorithm improves the signal to noise ratio. OCTA is considered a reliable tool in the detection and quantification of macular ischemia in diabetics.~In this study, the investigators aim to compare the effect of repeated intravitreal injections of ranibizumab and bevacizumab on the perfusion of different capillary layers in the macula of diabetic patients using OCTA.
|
Diabetic retinopathy is the major cause of blindness in developed but also in developing countries. The disruption of the blood-retinal barrier and the subsequent accumulation of fluid in the intraretinal layers result in diabetic macular edema (DME), the leading cause of central vision loss in these patients.~The Early Treatment Diabetic Retinopathy Study (ETDRS) group founded guidelines for treating patients with clinically significant DME (CSME) with focal/grid macular laser photocoagulation. Since then, macular laser, and steroids, were the main therapies for treatment of DME until anti-vascular endothelial growth factors (anti-VEGF) drugs were developed after a growing body of scientific evidence implicated VEGF in the pathophysiologic process of DME.~Anti-VEGF drugs have been implicated in the treatment of DME. VEGF has been shown to play an important role in the occurrence of increased vascular permeability in DME. VEGF levels are significantly higher in patients with DME and extensive leakage than in patients with minimal leakage.~Many studies such as Diabetic Retinopathy Clinical Research [DRCR] Network studies, RESTORE Study, RISE and RIDE Research Group, and The BOLT Study have supported the use of anti-VEGF agents in the treatment of DME with better visual outcomes using anti-VEGF injections alone or in combination with other treatments.~DRCR network protocol T found statistically insignificant difference between ranibizumab and bevacizumab on visual acuity and central macular thickness in diabetic macular edema.~Several ocular complications of intravitreal anti-VEGF injections have been reported including endophthalmitis, cataract, and retinal detachment. The different effects on macular perfusion between different anti-VEGFs have yet to be fully concluded with mixed conclusions that it increases or decreases or has no effect on perfusion of macula in response to Anti-VEGF treatment.in many of these studies, however, patients with more ischemic retinas were not included. Retinal ischemia is a vital factor determining the diabetic retinopathy progression and prognosis.~Using ocular ultrasound some studies showed retinal arteriolar vasoconstriction in eyes treated with anti-VEGF, while others showed decreased blood flow velocities in all retro-bulbar arteries after intravitreal injection of anti-VEGF. This may indicate that anti-VEGF may have an effect on ocular perfusion.~Fluorescein angiography (FA) was the method used to assess changes in macular perfusion after anti-VEGF injections in most of the studies. Despite its clinical value, however, FA is known to have documented risks. Optical coherence tomography angiography (OCTA) is an excellent non-invasive modality to acquire high-resolution images of the retinal vasculature that can be utilized in the treatment of retinal disease without the need for dye injection. It allows the visualization of both the superficial and deep retinal capillary layers separately and the construction of microvascular flow maps.~OCTA detects blood flow by analyzing signal decorrelation between two sequential OCT cross-sectional scans at the same location. As it detects the movements of red blood corpuscles within the vessels, compared to the stationary retinal surroundings, which will result in signal disparity and imaging The split-spectrum amplitude-decorrelation angiography (SSADA) algorithm improves the signal to noise ratio. OCTA is considered a reliable tool in the detection and quantification of macular ischemia in diabetics.~In this study, the investigators aim to compare the effect of repeated intravitreal injections of ranibizumab and bevacizumab on the perfusion of different capillary layers in the macula of diabetic patients using OCTA.
|
Comparison of the Effect of Ranibizumab Versus Bevacizumab on the Macular Perfusion in Diabetic Macular Edema Using OCTA
|
Diabetic Macular Edema, Macular Ischemia, Diabetic Retinopathy, Vascular Endothelial Growth Factor Overexpression
|
* Drug: Intravitreal ranibizumab
* Drug: Intravitreal bevacizumab
|
Inclusion Criteria:~Patients ≥18 years old with type 1 or 2 diabetes mellitus with decreased BCVA due to center involving diabetic macular edema on spectral-domain optical coherence tomography.~Patients with central macular thickness CMT of ≥ 300 micrometers~Exclusion Criteria:~Ocular conditions that may affect macular perfusion (e.g. retinal vascular diseases, uveitis, vasculitis etc.)~History of vitreo-retinal surgeries.~Previous macular laser treatment~Presence of epi-retinal membrane involving the macula or vitreo-macular traction.~Media opacity preventing good image quality.~Uncontrolled glaucoma.~Thrombo-embolic events within 6 months~Previous intravitreal injections of anti-VEGF
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in foveal avascular zone area | The change in the foveal avascular zone area will be compared between the two treatment arms as a measure of macular perfusion change. | 0 and 3 months. |
| Change in vascular density of the superficial retinal capillary plexus | The change in the superficial retinal capillary plexus vascular density will be compared between the two treatment arms as a measure of macular perfusion change. | 0 and 3 months. |
| Change in vascular density of the deep retinal capillary plexus | The change in the deep retinal capillary plexus vascular density will be compared between the two treatment arms as a measure of macular perfusion change. | 0 and 3 months. |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in best corrected visual acuity | The change in best corrected visual acuity will be assessed following treatment with both drugs using standard Snellen charts. | 0 and 3 months |
| Change in central macular thickness | The change in central macular thickness will be assessed following treatment with both drugs using optical coherence tomography. | 0 and 3 months |
| Change in intraocular pressure | he change in intraocular pressure will be assessed following treatment with both drugs using Goldman applanation tonometry. | 0 and 3 months |
| Change of severity of diabetic retinopathy | The change in the severity of diabetic retinopathy will be assessed following treatment with both drugs using color fundus photographs and clinical examination. | 0 and 3 months |
|
Diabetic macular edema, Macular perfusion, Optical coherence tomography angiography, Anti-VEGF
|
Bevacizumab, Ranibizumab, Antineoplastic Agents, Immunological, Antineoplastic Agents, Angiogenesis Inhibitors, Angiogenesis Modulating Agents, Growth Substances, Physiological Effects of Drugs, Growth Inhibitors
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ranibizumab Group<br>Patients will receive monthly ranibizumab injections for 3 months. | Drug: Intravitreal ranibizumab<br>* Intravitreal injection of 0.3 mg/0.05 ml ranibizumab will be performed monthly for 3 months.<br>* Other names: Lucentis;|
| Active Comparator: Bevacizumab Group<br>Patients will receive monthly bevacizumab injections for 3 months. | Drug: Intravitreal bevacizumab<br>* Intravitreal injection of 1.25 mg/0.05 ml bevacizumab will be performed monthly for 3 months.<br>* Other names: Avastin;|
|
Effect of Ranibizumab Versus Bevacizumab on the Macular Perfusion in Diabetic Macular Edema
Study Overview
=================
Brief Summary
-----------------
The Early Treatment Diabetic Retinopathy Study (ETDRS) group founded guidelines for treating patients with clinically significant diabetic macular edema (DME) with focal/grid macular laser photocoagulation. Since then, macular laser, and steroids, were the main therapies for the treatment of DME until anti-vascular endothelial growth factors (anti-VEGF) drugs were developed after a growing body of scientific evidence implicated VEGF in the pathophysiologic process of DME. Anti-VEGF drugs have been implicated in the treatment of DME. VEGF has been shown to play an important role in the occurrence of increased vascular permeability in DME. VEGF levels are significantly higher in patients with DME and extensive leakage than in patients with minimal leakage. Many studies such as Diabetic Retinopathy Clinical Research [DRCR] Network studies, RESTORE Study, RISE and RIDE Research Group, and The BOLT Study have supported the use of anti-VEGF agents in the treatment of DME with better visual outcomes using anti-VEGF injections alone or in combination with other treatments. Several ocular complications of intravitreal anti-VEGF injections have been reported including endophthalmitis, cataract, and retinal detachment. The different effects on macular perfusion between different anti-VEGFs have yet to be fully concluded with mixed conclusions that it increases or decreases or has no effect on perfusion of the macula in response to Anti-VEGF treatment. In many of these studies, however, patients with more ischemic retinas were not included. Retinal ischemia is a vital factor determining the diabetic retinopathy progression and prognosis. Optical coherence tomography angiography (OCTA) detects blood flow by analyzing signal decorrelation between two sequential OCT cross-sectional scans at the same location. As it detects the movements of red blood corpuscles within the vessels, compared to the stationary retinal surroundings, which will result in signal disparity and imaging The split-spectrum amplitude-decorrelation angiography (SSADA) algorithm improves the signal to noise ratio. OCTA is considered a reliable tool in the detection and quantification of macular ischemia in diabetics. In this study, the investigators aim to compare the effect of repeated intravitreal injections of ranibizumab and bevacizumab on the perfusion of different capillary layers in the macula of diabetic patients using OCTA.
Detailed Description
-----------------
Diabetic retinopathy is the major cause of blindness in developed but also in developing countries. The disruption of the blood-retinal barrier and the subsequent accumulation of fluid in the intraretinal layers result in diabetic macular edema (DME), the leading cause of central vision loss in these patients. The Early Treatment Diabetic Retinopathy Study (ETDRS) group founded guidelines for treating patients with clinically significant DME (CSME) with focal/grid macular laser photocoagulation. Since then, macular laser, and steroids, were the main therapies for treatment of DME until anti-vascular endothelial growth factors (anti-VEGF) drugs were developed after a growing body of scientific evidence implicated VEGF in the pathophysiologic process of DME. Anti-VEGF drugs have been implicated in the treatment of DME. VEGF has been shown to play an important role in the occurrence of increased vascular permeability in DME. VEGF levels are significantly higher in patients with DME and extensive leakage than in patients with minimal leakage. Many studies such as Diabetic Retinopathy Clinical Research [DRCR] Network studies, RESTORE Study, RISE and RIDE Research Group, and The BOLT Study have supported the use of anti-VEGF agents in the treatment of DME with better visual outcomes using anti-VEGF injections alone or in combination with other treatments. DRCR network protocol T found statistically insignificant difference between ranibizumab and bevacizumab on visual acuity and central macular thickness in diabetic macular edema. Several ocular complications of intravitreal anti-VEGF injections have been reported including endophthalmitis, cataract, and retinal detachment. The different effects on macular perfusion between different anti-VEGFs have yet to be fully concluded with mixed conclusions that it increases or decreases or has no effect on perfusion of macula in response to Anti-VEGF treatment.in many of these studies, however, patients with more ischemic retinas were not included. Retinal ischemia is a vital factor determining the diabetic retinopathy progression and prognosis. Using ocular ultrasound some studies showed retinal arteriolar vasoconstriction in eyes treated with anti-VEGF, while others showed decreased blood flow velocities in all retro-bulbar arteries after intravitreal injection of anti-VEGF. This may indicate that anti-VEGF may have an effect on ocular perfusion. Fluorescein angiography (FA) was the method used to assess changes in macular perfusion after anti-VEGF injections in most of the studies. Despite its clinical value, however, FA is known to have documented risks. Optical coherence tomography angiography (OCTA) is an excellent non-invasive modality to acquire high-resolution images of the retinal vasculature that can be utilized in the treatment of retinal disease without the need for dye injection. It allows the visualization of both the superficial and deep retinal capillary layers separately and the construction of microvascular flow maps. OCTA detects blood flow by analyzing signal decorrelation between two sequential OCT cross-sectional scans at the same location. As it detects the movements of red blood corpuscles within the vessels, compared to the stationary retinal surroundings, which will result in signal disparity and imaging The split-spectrum amplitude-decorrelation angiography (SSADA) algorithm improves the signal to noise ratio. OCTA is considered a reliable tool in the detection and quantification of macular ischemia in diabetics. In this study, the investigators aim to compare the effect of repeated intravitreal injections of ranibizumab and bevacizumab on the perfusion of different capillary layers in the macula of diabetic patients using OCTA.
Official Title
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Comparison of the Effect of Ranibizumab Versus Bevacizumab on the Macular Perfusion in Diabetic Macular Edema Using OCTA
Conditions
-----------------
Diabetic Macular Edema, Macular Ischemia, Diabetic Retinopathy, Vascular Endothelial Growth Factor Overexpression
Intervention / Treatment
-----------------
* Drug: Intravitreal ranibizumab
* Drug: Intravitreal bevacizumab
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients ≥18 years old with type 1 or 2 diabetes mellitus with decreased BCVA due to center involving diabetic macular edema on spectral-domain optical coherence tomography. Patients with central macular thickness CMT of ≥ 300 micrometers Exclusion Criteria: Ocular conditions that may affect macular perfusion (e.g. retinal vascular diseases, uveitis, vasculitis etc.) History of vitreo-retinal surgeries. Previous macular laser treatment Presence of epi-retinal membrane involving the macula or vitreo-macular traction. Media opacity preventing good image quality. Uncontrolled glaucoma. Thrombo-embolic events within 6 months Previous intravitreal injections of anti-VEGF
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ranibizumab Group<br>Patients will receive monthly ranibizumab injections for 3 months. | Drug: Intravitreal ranibizumab<br>* Intravitreal injection of 0.3 mg/0.05 ml ranibizumab will be performed monthly for 3 months.<br>* Other names: Lucentis;|
| Active Comparator: Bevacizumab Group<br>Patients will receive monthly bevacizumab injections for 3 months. | Drug: Intravitreal bevacizumab<br>* Intravitreal injection of 1.25 mg/0.05 ml bevacizumab will be performed monthly for 3 months.<br>* Other names: Avastin;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in foveal avascular zone area | The change in the foveal avascular zone area will be compared between the two treatment arms as a measure of macular perfusion change. | 0 and 3 months. |
| Change in vascular density of the superficial retinal capillary plexus | The change in the superficial retinal capillary plexus vascular density will be compared between the two treatment arms as a measure of macular perfusion change. | 0 and 3 months. |
| Change in vascular density of the deep retinal capillary plexus | The change in the deep retinal capillary plexus vascular density will be compared between the two treatment arms as a measure of macular perfusion change. | 0 and 3 months. |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in best corrected visual acuity | The change in best corrected visual acuity will be assessed following treatment with both drugs using standard Snellen charts. | 0 and 3 months |
| Change in central macular thickness | The change in central macular thickness will be assessed following treatment with both drugs using optical coherence tomography. | 0 and 3 months |
| Change in intraocular pressure | he change in intraocular pressure will be assessed following treatment with both drugs using Goldman applanation tonometry. | 0 and 3 months |
| Change of severity of diabetic retinopathy | The change in the severity of diabetic retinopathy will be assessed following treatment with both drugs using color fundus photographs and clinical examination. | 0 and 3 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Diabetic macular edema, Macular perfusion, Optical coherence tomography angiography, Anti-VEGF
|
NCT01846260
|
Predictive Value of the Distress Thermometer as a Predictive Screening Instrument to Detect Cancer-related Cognitive Impairment in Cancer Patients
|
Cognitive impairment associated with chemotherapy is an important reported post-treatment side-effect among breast and other cancer survivors. As some patients report cognitive complaints before the administration of their therapy, some authors suggest an association with psychological risk factors such as distress. Distress, a multifactorial unpleasant emotional experience of a psychological (cognitive, behavioral and emotional), social and/or spiritual nature that may interfere with the ability to cope with cancer effectively, its physical symptoms and its treatment, can easily be assessed by the Distress Thermometer.~In this trial we aim to determine if the Distress Thermometer, accompanied by the 38-item Problem List, could predict cancer-related cognitive impairment in patients with hematologic malignancies, and in patients with gynecological, urological, breast, lung or gastro-intestinal cancer receiving curative radiotherapy, chemotherapy, radiochemotherapy, anti-hormonal or targeted therapy.
|
Design: Prospective, observational study. All cancer patients of the above mentioned cancer types receiving an anticancer treatment with curative intent will be asked to participate to this study. Consenting patients will undergo serial assessment at baseline, and 6 months after inclusion. Patient will be screened by the Distress Thermometer and 38-item Problem List followed by a neuropsychological assessment and self-assessment tools.
|
Predictive Value of the Distress Thermometer as a Predictive Screening Instrument to Detect Cancer-related Cognitive Impairment in Cancer Patients
|
Cancer Patients Eligible for a Treatment With Curative Intent, Cognitive Impairment
|
Inclusion Criteria:~Patients should have reached a minimum age of 18 years at the time of enrolment~Newly detected histologically confirmed diagnosis of a solid (lung, gastro-intestinal, GIST, urological, prostate, breast, sarcoma or gynecological cancer) or hematologic malignancy~Patients should receive a treatment with curative intent based on the investigator's judgment or have an expected median overall survival of at least 5 years~Patients scheduled to receive (adjuvant) radiotherapy, chemotherapy, radiobiotherapy, radiochemotherapy, anti-hormonal or targeted therapy with curative intent~Patients should be able to adequately communicate in Dutch~Patients should present with a sufficient mental and physical functional status (according to investigator's judgment and first baseline assessment) for completing the questionnaires and neuropsychological assessment~Exclusion Criteria:~Patients younger than 18 at the time of enrollment~Patients who present with a cognitive impairment~Patient receiving a treatment with palliative intent~Patients who had surgery in the three weeks preceding the baseline assessment~Patients diagnosed with primary or secondary brain tumors~Patients with a prior history of cancer during the last 5 years, with or without chemotherapy or radiotherapy~Patients suffering from organic brain disease~Patients with an untreated or unstable major medical condition~Patients who are alcohol or drug dependent~Patients showing signs of mental deterioration~Patients with dementia (DSM-IV criteria)~Patients with a major psychiatric or neurologic disorder that could potentially invalidate assessment; a prior or current diagnosis of a depressive or anxiety disorder is allowed~Patients presenting with a condition other than cancer in which fatigue is a prominent symptom (such as chronic fatigue symptom)
|
18 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Validation of the Distress Thermometer, accompanied by the 38-item Problem List, as a screening tool to predict cancer-related cognitive impairment, measured through standard neuropsychological testing | The primary objective of this observational study is to validate the Distress Thermometer, accompanied by the 38-item Problem List, as a screening tool to predict cancer-related cognitive impairment, measured through standard neuropsychological testing in cancer patients receiving curative (adjuvant) radiotherapy, chemotherapy, radiochemotherapy, radiobiotherapy, or targeted therapy. | 6 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of cognitive impairments and distress in all cancer patients included in this study and per cohort in a general hospital in Belgium by use of the Distress Thermometer and neuropsychological assessment | | 6 months |
| Comparison of subjective patient reported symptoms through self-reported measurements with objective neurocognitive test results and to examine the feasibility of these self-report assessment | | 6 months |
| Evaluation of the performance of the distress thermometer to detect cancer-related cognitive impairments over time | | 6 months |
| Determination of a cut-off score for the Distress Thermometer as a screening tool to detect cancer-related cognitive impairments over time by use of Receiver Operating Characteristics (ROC) curve | | 6 months |
| Evaluation of distress scores compared to patients' quality of life post-treatment by use of EORTC QLQ C-30 | | 2 years |
|
Cognitive Dysfunction, Cognition Disorders, Neurocognitive Disorders, Mental Disorders
|
Predictive Value of the Distress Thermometer as a Predictive Screening Instrument to Detect Cancer-related Cognitive Impairment in Cancer Patients
Study Overview
=================
Brief Summary
-----------------
Cognitive impairment associated with chemotherapy is an important reported post-treatment side-effect among breast and other cancer survivors. As some patients report cognitive complaints before the administration of their therapy, some authors suggest an association with psychological risk factors such as distress. Distress, a multifactorial unpleasant emotional experience of a psychological (cognitive, behavioral and emotional), social and/or spiritual nature that may interfere with the ability to cope with cancer effectively, its physical symptoms and its treatment, can easily be assessed by the Distress Thermometer. In this trial we aim to determine if the Distress Thermometer, accompanied by the 38-item Problem List, could predict cancer-related cognitive impairment in patients with hematologic malignancies, and in patients with gynecological, urological, breast, lung or gastro-intestinal cancer receiving curative radiotherapy, chemotherapy, radiochemotherapy, anti-hormonal or targeted therapy.
Detailed Description
-----------------
Design: Prospective, observational study. All cancer patients of the above mentioned cancer types receiving an anticancer treatment with curative intent will be asked to participate to this study. Consenting patients will undergo serial assessment at baseline, and 6 months after inclusion. Patient will be screened by the Distress Thermometer and 38-item Problem List followed by a neuropsychological assessment and self-assessment tools.
Official Title
-----------------
Predictive Value of the Distress Thermometer as a Predictive Screening Instrument to Detect Cancer-related Cognitive Impairment in Cancer Patients
Conditions
-----------------
Cancer Patients Eligible for a Treatment With Curative Intent, Cognitive Impairment
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients should have reached a minimum age of 18 years at the time of enrolment Newly detected histologically confirmed diagnosis of a solid (lung, gastro-intestinal, GIST, urological, prostate, breast, sarcoma or gynecological cancer) or hematologic malignancy Patients should receive a treatment with curative intent based on the investigator's judgment or have an expected median overall survival of at least 5 years Patients scheduled to receive (adjuvant) radiotherapy, chemotherapy, radiobiotherapy, radiochemotherapy, anti-hormonal or targeted therapy with curative intent Patients should be able to adequately communicate in Dutch Patients should present with a sufficient mental and physical functional status (according to investigator's judgment and first baseline assessment) for completing the questionnaires and neuropsychological assessment Exclusion Criteria: Patients younger than 18 at the time of enrollment Patients who present with a cognitive impairment Patient receiving a treatment with palliative intent Patients who had surgery in the three weeks preceding the baseline assessment Patients diagnosed with primary or secondary brain tumors Patients with a prior history of cancer during the last 5 years, with or without chemotherapy or radiotherapy Patients suffering from organic brain disease Patients with an untreated or unstable major medical condition Patients who are alcohol or drug dependent Patients showing signs of mental deterioration Patients with dementia (DSM-IV criteria) Patients with a major psychiatric or neurologic disorder that could potentially invalidate assessment; a prior or current diagnosis of a depressive or anxiety disorder is allowed Patients presenting with a condition other than cancer in which fatigue is a prominent symptom (such as chronic fatigue symptom)
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Validation of the Distress Thermometer, accompanied by the 38-item Problem List, as a screening tool to predict cancer-related cognitive impairment, measured through standard neuropsychological testing | The primary objective of this observational study is to validate the Distress Thermometer, accompanied by the 38-item Problem List, as a screening tool to predict cancer-related cognitive impairment, measured through standard neuropsychological testing in cancer patients receiving curative (adjuvant) radiotherapy, chemotherapy, radiochemotherapy, radiobiotherapy, or targeted therapy. | 6 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of cognitive impairments and distress in all cancer patients included in this study and per cohort in a general hospital in Belgium by use of the Distress Thermometer and neuropsychological assessment | | 6 months |
| Comparison of subjective patient reported symptoms through self-reported measurements with objective neurocognitive test results and to examine the feasibility of these self-report assessment | | 6 months |
| Evaluation of the performance of the distress thermometer to detect cancer-related cognitive impairments over time | | 6 months |
| Determination of a cut-off score for the Distress Thermometer as a screening tool to detect cancer-related cognitive impairments over time by use of Receiver Operating Characteristics (ROC) curve | | 6 months |
| Evaluation of distress scores compared to patients' quality of life post-treatment by use of EORTC QLQ C-30 | | 2 years |
|
||||
NCT03329092
|
A Study to Determine the Efficacy, Safety and Tolerability of Aztreonam-Avibactam (ATM-AVI) ± Metronidazole (MTZ) Versus Meropenem (MER) ± Colistin (COL) for the Treatment of Serious Infections Due to Gram Negative Bacteria.
|
A Phase 3 comparative study to determine the efficacy, safety and tolerability of Aztreonam-Avibactam (ATM-AVI) ± Metronidazole (MTZ) versus Meropenem (MER) ± Colistin (COL) for the treatment of serious infections due to Gram negative bacteria.
|
A Phase 3 Prospective, Randomized, Multicenter, Open Label, Central Assessor Blinded, Parallel Group, Comparative Study To Determine The Efficacy, Safety And Tolerability Of Aztreonam-Avibactam (ATM-AVI) ± Metronidazole (MTZ) Versus Meropenem±Colistin (MER±COL) For The Treatment Of Serious Infections Due To Gram Negative Bacteria, Including Metallo Β Lactamase (MBL) - Producing Multidrug Resistant Pathogens, For Which There Are Limited Or No Treatment Options
|
A PHASE 3 PROSPECTIVE, RANDOMIZED, MULTICENTER, OPEN-LABEL, CENTRAL ASSESSOR-BLINDED, PARALLEL GROUP, COMPARATIVE STUDY TO DETERMINE THE EFFICACY, SAFETY AND TOLERABILITY OF AZTREONAM-AVIBACTAM (ATM-AVI) ±METRONIDAZOLE (MTZ) VERSUS MEROPENEM±COLISTIN (MER±COL) FOR THE TREATMENT OF SERIOUS INFECTIONS DUE TO GRAM NEGATIVE BACTERIA, INCLUDING METALLO-Β-LACTAMASE (MBL) - PRODUCING MULTIDRUG RESISTANT PATHOGENS, FOR WHICH THERE ARE LIMITED OR NO TREATMENT OPTIONS
|
Complicated Intra-abdominal Infection, Hosptial Acquired Pneumonia, Ventilator Associated Pneumonia
|
* Drug: ATM-AVI
* Drug: MTZ
* Drug: MER
* Drug: COL
|
Inclusion Criteria:~All subjects:~Male or female from 18 years of age~Provision of informed consent~Confirmed diagnosis of HAP/VAP or cIAI requiring iv antibiotic treatment~Female patients are authorized to participate in this clinical study if criteria concerning pregnancy avoidance stated in the protocol are met and negative pregnancy test~Additional for cIAI:~Diagnosis of cIAI, EITHER:~Intra-operative/postoperative enrolment with visual confirmation of cIAI. OR Preoperative enrollment with evidence of systemic inflammatory response, physical and radiological findings consistent with cIAI; confirmation of cIAI at time of surgery within 24 hours of study entry~Surgical intervention within 24 hours (before or after) the administration of the first dose of study drug~Additional for HAP/VAP:~Onset symptoms > 48h after admission to or <7 days after discharge from an inpatient care facility~New or worsening infiltrate on CXR or CT scan~Clinical signs and symptoms and laboratory findings consistent with HAP/VAP~Respiratory specimen obtained for Gram stain and culture following onset of symptoms and prior to randomisation~Exclusion criteria:~All subjects:~APACHE II score > 30~Confirmed or suspected infection caused by Gram-negative species not expected to respond to study drug, or Gram-positive species~Receipt of >24 hr systemic antibiotic within 48h prior to randomisation (exception in case of treatment failure)~History of serious allergy, hypersensitivity (eg, anaphylaxis), or any serious reaction to aztreonam, carbapenem,monobactam or other β-lactam antibiotics, avibactam, nitroimidazoles or metronidazole, or any of the excipients of the study drugs~Known Clostridium difficle associated diarrhoea~Requirement for effective concomitant systemic antibacterials or antifungals~Creatinine clearance ≤15 ml/min or requirement or expectation for renal replacement therapy~Acute hepatitis, cirrhosis, acute hepatic failure, chronic hepatic failure~Hepatic disease as indicated by AST or ALT >3 × ULN. Patients with AST and/or ALT up to 5 × ULN are eligible if acute and documented by the investigator as being directly related infectious process~Patient has a total bilirubin >2 × ULN, unless isolated hyperbilirubinemia is directly related to infectious process or due to known Gilbert's disease~ALP >3 × ULN. Patients with values >3 × ULN and <5 x ULN are eligible if acute and directly related to the infectious process being treated~Absolute neutrophil count <500/mm3~Pregnant or breastfeeding or if of child bearing potential, not using a medically accepted effective method of birth control.~Any other condition that may confound the results of the study or pose additional risks to the subject~Unlikely to comply with protocol~History of epilepsy or seizure disorders excluding febrile seizures of childhood~Additional for cIAI~Diagnosis of abdominal wall abscess; small bowel obstruction or ischemic bowel disease without perforation; traumatic bowel perforation with surgery within 12 hours of diagnosis; perforation of gastroduodenal ulcer with surgery < 24 hours of diagnosis primary etiology is not likely to be infectious~Simple cholecystitis, gangrenous cholecystitis without rupture, simple appendicitis, acute suppurative cholangitis, infected necrotizing pancreatitis, pancreatic abscess~Prior liver, pancreas or small-bowel transplant~Staged abdominal repair (STAR), open abdomen technique or marsupialisation~Additional for HAP/VAP~APACHE II score < 10~Known or high likelihood of Gram-positive monomicrobial infection~Lung abscess, pleural empyema, post-obstructive pneumonia~Lung or heart transplant~Myasthenia gravis
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective, Randomized, Multicenter, Open Label, Central Assessor Blinded, Parallel Group, Comparative Study
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with clinical cure in the ITT and CE analysis sets | Proportion of subjects meeting the criteria for clinical cure | Test of Cure (TOC) visit, Day 28 +/- 3 days |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with clinical cure in the m-ITT and ME analysis sets | Proportion of subjects meeting the criteria for clinical cure | Test of Cure (TOC) visit, Day 28 (+/- 3 days) |
| Proportion of subjects with clinical cure by infection type in the ITT and CE analysis sets. | Proportion of subjects meeting the criteria for clinical cure | Test of Cure (TOC) visit, Day 28 (+/- 3 days) |
| Proportion of subjects with clinical cure for subjects with MBL positive pathogens in the micro ITT and ME analysis sets. | Proportion of subjects meeting the criteria for clinical cure | Test of Cure (TOC) visit, Day 28 (+/- 3 days) |
| Proportion of subjects with a favorable per subject microbiological response in the micro ITT and ME analysis sets. | Proportion of subjects with a favourable microbiological response (aggregate of eradication + presumed eradication) | Test of Cure (TOC) visit, Day 28 (+/- 3 days) |
| Proportion of subjects who died | Daily mortality assessment | Day 28 |
| PK of ATM | Plasma concentration of ATM | Days 1 and 4 |
| PK/PD relationship between exposure and clinical response for ATM AVI±MTZ in the popPK analysis set | Correlation between plasma concentration of ATM and clinical cure | Test of Cure (TOC) visit, Day 28 (+/- 3 days) |
| PK of AVI | Plasma concentration of AVI | Days 1 and 4 |
| PK/PD relationship between exposure and clinical response for ATM/AVI +/- MTZ in the popPK analysis set | Correlation between concentration of AVI and clinical cure | Test of Cure (TOC) days 28 (+/- 3 days) |
| PK/PD relationship between exposure and microbiological response for ATM/AVI+/-MTZ in the popPK analysis set | Correlation between plasma concentration of ATM and microbiological response | Test of Cure (TOC) visit, Days 28 (+/- 3 days) |
| PK/PD relationship between exposure and microbiological response for ATM/AVI+/-MTZ in the popPK analysis set | Correlation between plasma concentration of AVI and microbiological response | Test of Cure (TOC) visit, day 28 (+/- 3 days) |
| Description of safety in terms of adverse events | Descriptive summary of adverse events | Throughout study to Late Follow Up visit (Day 45 +/- 3 days) |
|
Complicated intra-abdominal infection, Hosptial acquired pneumonia, Ventilator associated pneumonia, Gram negative infections, Metallo-beta lactamase, Multi drug resistant pathogens
|
Infections, Communicable Diseases, Pneumonia, Pneumonia, Ventilator-Associated, Intraabdominal Infections, Disease Attributes, Pathologic Processes, Respiratory Tract Infections, Lung Diseases, Respiratory Tract Diseases, Healthcare-Associated Pneumonia, Cross Infection, Iatrogenic Disease
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aztreonam-Avibactam ± Metronidazole<br>All patients randomised to this arm will receive ATM-AVI; all patients with cIAI will receive MTZ for anaerobic cover | Drug: ATM-AVI<br>* (Creatinine clearance > 50 mL/min) 6500 mg ATM/2167 mg (loading dose, extended loading dose and maintenance dose) by iv infusion on Day 1 followed by a total daily dose of 6000 mg ATM/2000 mg AVI~(Creatinine clearance 31 - 50 mL/min) 4250 mg ATM/1417 mg AVI on Day 1 (loading dose, extended loading dose, maintenance dose) followed by total daily dose 3000 mg ATM/1000 mg AVI~(Creatinine clearance 16 - 30 mL/min) 2700 mg ATM/900 mg AVI on Day 1 (loading dose, extended loading dose maintenance dose), followed by total daily dose 2025 mg ATM/675 mg AVI<br>Drug: MTZ<br>* For cIAI only; 500 mg/100 mL metronidazole iv infusion over 1hr q8h<br>|
| Active Comparator: Meropenem ± Colistin<br>All patients randomised to this arm will receive MER; addition of COL will be at investigator's discretion in line with local practice | Drug: MER<br>* Where pathogen initially not suspected of being MER-resistant:~(Creatinine clearance > 50 mL/min) 1000 mg meropenem by 30 min iv infusion q8h~(Creatinine clearance 26 - 50 mL/min) 1000mg meropenem by 30 min iv infusion q12h~(Creatinine clearance 16 - 25 mL/min) 500 mg meropenem by 30 min iv infusion q12h~Where pathogen initially suspected of being MER-resistant (Creatinine clearance > 50 mL/min) 2000 mg meropenem by 180 min iv infusion q8h~(Creatinine clearance 26 - 50 mL/min) 2000 mg meropenem by 180 min iv infusion q12h~(Creatinine clearance 16 - 25 mL/min) 1000 mg meropenem by 180 min iv infusion q12h<br>Drug: COL<br>* Loading dose 9 million IU by 30 -60 min iv infusion (6 million IU where weight < 60 kg) followed by one of the following maintenance doses:~(Creatinine clearance > 50 mL/min) after a 12h interval, commence maintenance dosing 9 million IU daily in 2 or 3 divided doses by 30 -60 min iv infusions.~(Creatinine clearance 31 - 50 mL/min) After a 24 hr interval, commence maintenance dosing of 6 million IU daily in 2 divided doses by 30 -60 min iv infusion~(Creatinine clearance 21 - 30 mL/min) After a 24 hr interval, commence maintenance dosing 5 million IU daily in 2 divided doses by 30 -60 min iv infusion~(Creatinine clearance 16 - 20 mL/min) after a 24 hr interval, commence maintenance dosing 4 million IU daily in 2 divided doses by 30 -60 min iv infusion<br>|
|
A Study to Determine the Efficacy, Safety and Tolerability of Aztreonam-Avibactam (ATM-AVI) ± Metronidazole (MTZ) Versus Meropenem (MER) ± Colistin (COL) for the Treatment of Serious Infections Due to Gram Negative Bacteria.
Study Overview
=================
Brief Summary
-----------------
A Phase 3 comparative study to determine the efficacy, safety and tolerability of Aztreonam-Avibactam (ATM-AVI) ± Metronidazole (MTZ) versus Meropenem (MER) ± Colistin (COL) for the treatment of serious infections due to Gram negative bacteria.
Detailed Description
-----------------
A Phase 3 Prospective, Randomized, Multicenter, Open Label, Central Assessor Blinded, Parallel Group, Comparative Study To Determine The Efficacy, Safety And Tolerability Of Aztreonam-Avibactam (ATM-AVI) ± Metronidazole (MTZ) Versus Meropenem±Colistin (MER±COL) For The Treatment Of Serious Infections Due To Gram Negative Bacteria, Including Metallo Β Lactamase (MBL) - Producing Multidrug Resistant Pathogens, For Which There Are Limited Or No Treatment Options
Official Title
-----------------
A PHASE 3 PROSPECTIVE, RANDOMIZED, MULTICENTER, OPEN-LABEL, CENTRAL ASSESSOR-BLINDED, PARALLEL GROUP, COMPARATIVE STUDY TO DETERMINE THE EFFICACY, SAFETY AND TOLERABILITY OF AZTREONAM-AVIBACTAM (ATM-AVI) ±METRONIDAZOLE (MTZ) VERSUS MEROPENEM±COLISTIN (MER±COL) FOR THE TREATMENT OF SERIOUS INFECTIONS DUE TO GRAM NEGATIVE BACTERIA, INCLUDING METALLO-Β-LACTAMASE (MBL) - PRODUCING MULTIDRUG RESISTANT PATHOGENS, FOR WHICH THERE ARE LIMITED OR NO TREATMENT OPTIONS
Conditions
-----------------
Complicated Intra-abdominal Infection, Hosptial Acquired Pneumonia, Ventilator Associated Pneumonia
Intervention / Treatment
-----------------
* Drug: ATM-AVI
* Drug: MTZ
* Drug: MER
* Drug: COL
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All subjects: Male or female from 18 years of age Provision of informed consent Confirmed diagnosis of HAP/VAP or cIAI requiring iv antibiotic treatment Female patients are authorized to participate in this clinical study if criteria concerning pregnancy avoidance stated in the protocol are met and negative pregnancy test Additional for cIAI: Diagnosis of cIAI, EITHER: Intra-operative/postoperative enrolment with visual confirmation of cIAI. OR Preoperative enrollment with evidence of systemic inflammatory response, physical and radiological findings consistent with cIAI; confirmation of cIAI at time of surgery within 24 hours of study entry Surgical intervention within 24 hours (before or after) the administration of the first dose of study drug Additional for HAP/VAP: Onset symptoms > 48h after admission to or <7 days after discharge from an inpatient care facility New or worsening infiltrate on CXR or CT scan Clinical signs and symptoms and laboratory findings consistent with HAP/VAP Respiratory specimen obtained for Gram stain and culture following onset of symptoms and prior to randomisation Exclusion criteria: All subjects: APACHE II score > 30 Confirmed or suspected infection caused by Gram-negative species not expected to respond to study drug, or Gram-positive species Receipt of >24 hr systemic antibiotic within 48h prior to randomisation (exception in case of treatment failure) History of serious allergy, hypersensitivity (eg, anaphylaxis), or any serious reaction to aztreonam, carbapenem,monobactam or other β-lactam antibiotics, avibactam, nitroimidazoles or metronidazole, or any of the excipients of the study drugs Known Clostridium difficle associated diarrhoea Requirement for effective concomitant systemic antibacterials or antifungals Creatinine clearance ≤15 ml/min or requirement or expectation for renal replacement therapy Acute hepatitis, cirrhosis, acute hepatic failure, chronic hepatic failure Hepatic disease as indicated by AST or ALT >3 × ULN. Patients with AST and/or ALT up to 5 × ULN are eligible if acute and documented by the investigator as being directly related infectious process Patient has a total bilirubin >2 × ULN, unless isolated hyperbilirubinemia is directly related to infectious process or due to known Gilbert's disease ALP >3 × ULN. Patients with values >3 × ULN and <5 x ULN are eligible if acute and directly related to the infectious process being treated Absolute neutrophil count <500/mm3 Pregnant or breastfeeding or if of child bearing potential, not using a medically accepted effective method of birth control. Any other condition that may confound the results of the study or pose additional risks to the subject Unlikely to comply with protocol History of epilepsy or seizure disorders excluding febrile seizures of childhood Additional for cIAI Diagnosis of abdominal wall abscess; small bowel obstruction or ischemic bowel disease without perforation; traumatic bowel perforation with surgery within 12 hours of diagnosis; perforation of gastroduodenal ulcer with surgery < 24 hours of diagnosis primary etiology is not likely to be infectious Simple cholecystitis, gangrenous cholecystitis without rupture, simple appendicitis, acute suppurative cholangitis, infected necrotizing pancreatitis, pancreatic abscess Prior liver, pancreas or small-bowel transplant Staged abdominal repair (STAR), open abdomen technique or marsupialisation Additional for HAP/VAP APACHE II score < 10 Known or high likelihood of Gram-positive monomicrobial infection Lung abscess, pleural empyema, post-obstructive pneumonia Lung or heart transplant Myasthenia gravis
Ages Eligible for Study
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Minimum Age: 18 Years
Sexes Eligible for Study
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All
Accepts Healthy Volunteers
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No
Study Plan
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How is the study designed?
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Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective, Randomized, Multicenter, Open Label, Central Assessor Blinded, Parallel Group, Comparative Study
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aztreonam-Avibactam ± Metronidazole<br>All patients randomised to this arm will receive ATM-AVI; all patients with cIAI will receive MTZ for anaerobic cover | Drug: ATM-AVI<br>* (Creatinine clearance > 50 mL/min) 6500 mg ATM/2167 mg (loading dose, extended loading dose and maintenance dose) by iv infusion on Day 1 followed by a total daily dose of 6000 mg ATM/2000 mg AVI (Creatinine clearance 31 - 50 mL/min) 4250 mg ATM/1417 mg AVI on Day 1 (loading dose, extended loading dose, maintenance dose) followed by total daily dose 3000 mg ATM/1000 mg AVI (Creatinine clearance 16 - 30 mL/min) 2700 mg ATM/900 mg AVI on Day 1 (loading dose, extended loading dose maintenance dose), followed by total daily dose 2025 mg ATM/675 mg AVI<br>Drug: MTZ<br>* For cIAI only; 500 mg/100 mL metronidazole iv infusion over 1hr q8h<br>|
| Active Comparator: Meropenem ± Colistin<br>All patients randomised to this arm will receive MER; addition of COL will be at investigator's discretion in line with local practice | Drug: MER<br>* Where pathogen initially not suspected of being MER-resistant: (Creatinine clearance > 50 mL/min) 1000 mg meropenem by 30 min iv infusion q8h (Creatinine clearance 26 - 50 mL/min) 1000mg meropenem by 30 min iv infusion q12h (Creatinine clearance 16 - 25 mL/min) 500 mg meropenem by 30 min iv infusion q12h Where pathogen initially suspected of being MER-resistant (Creatinine clearance > 50 mL/min) 2000 mg meropenem by 180 min iv infusion q8h (Creatinine clearance 26 - 50 mL/min) 2000 mg meropenem by 180 min iv infusion q12h (Creatinine clearance 16 - 25 mL/min) 1000 mg meropenem by 180 min iv infusion q12h<br>Drug: COL<br>* Loading dose 9 million IU by 30 -60 min iv infusion (6 million IU where weight < 60 kg) followed by one of the following maintenance doses: (Creatinine clearance > 50 mL/min) after a 12h interval, commence maintenance dosing 9 million IU daily in 2 or 3 divided doses by 30 -60 min iv infusions. (Creatinine clearance 31 - 50 mL/min) After a 24 hr interval, commence maintenance dosing of 6 million IU daily in 2 divided doses by 30 -60 min iv infusion (Creatinine clearance 21 - 30 mL/min) After a 24 hr interval, commence maintenance dosing 5 million IU daily in 2 divided doses by 30 -60 min iv infusion (Creatinine clearance 16 - 20 mL/min) after a 24 hr interval, commence maintenance dosing 4 million IU daily in 2 divided doses by 30 -60 min iv infusion<br>|
What is the study measuring?
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Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with clinical cure in the ITT and CE analysis sets | Proportion of subjects meeting the criteria for clinical cure | Test of Cure (TOC) visit, Day 28 +/- 3 days |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with clinical cure in the m-ITT and ME analysis sets | Proportion of subjects meeting the criteria for clinical cure | Test of Cure (TOC) visit, Day 28 (+/- 3 days) |
| Proportion of subjects with clinical cure by infection type in the ITT and CE analysis sets. | Proportion of subjects meeting the criteria for clinical cure | Test of Cure (TOC) visit, Day 28 (+/- 3 days) |
| Proportion of subjects with clinical cure for subjects with MBL positive pathogens in the micro ITT and ME analysis sets. | Proportion of subjects meeting the criteria for clinical cure | Test of Cure (TOC) visit, Day 28 (+/- 3 days) |
| Proportion of subjects with a favorable per subject microbiological response in the micro ITT and ME analysis sets. | Proportion of subjects with a favourable microbiological response (aggregate of eradication + presumed eradication) | Test of Cure (TOC) visit, Day 28 (+/- 3 days) |
| Proportion of subjects who died | Daily mortality assessment | Day 28 |
| PK of ATM | Plasma concentration of ATM | Days 1 and 4 |
| PK/PD relationship between exposure and clinical response for ATM AVI±MTZ in the popPK analysis set | Correlation between plasma concentration of ATM and clinical cure | Test of Cure (TOC) visit, Day 28 (+/- 3 days) |
| PK of AVI | Plasma concentration of AVI | Days 1 and 4 |
| PK/PD relationship between exposure and clinical response for ATM/AVI +/- MTZ in the popPK analysis set | Correlation between concentration of AVI and clinical cure | Test of Cure (TOC) days 28 (+/- 3 days) |
| PK/PD relationship between exposure and microbiological response for ATM/AVI+/-MTZ in the popPK analysis set | Correlation between plasma concentration of ATM and microbiological response | Test of Cure (TOC) visit, Days 28 (+/- 3 days) |
| PK/PD relationship between exposure and microbiological response for ATM/AVI+/-MTZ in the popPK analysis set | Correlation between plasma concentration of AVI and microbiological response | Test of Cure (TOC) visit, day 28 (+/- 3 days) |
| Description of safety in terms of adverse events | Descriptive summary of adverse events | Throughout study to Late Follow Up visit (Day 45 +/- 3 days) |
Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Complicated intra-abdominal infection, Hosptial acquired pneumonia, Ventilator associated pneumonia, Gram negative infections, Metallo-beta lactamase, Multi drug resistant pathogens
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NCT03483103
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Lisocabtagene Maraleucel (JCAR017) as Second-Line Therapy (TRANSCEND-PILOT-017006)
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This is a Phase 2, open-label, multicenter study to determine the efficacy and safety of lisocabtagene maraleucel (JCAR017) in adult subjects who have relapsed from, or are refractory to, a single line of immunochemotherapy for aggressive B-cell non-Hodgkin lymphoma (NHL) and are ineligible for hematopoietic stem cell transplant (based on age, performance status, and/or comorbidities). Subjects will receive treatment with lisocabtagene maraleucel and will be followed for 2 years for safety, pharmacokinetics and biomarkers, disease status, quality of life, and survival.
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A Phase 2 Study of Lisocabtagene Maraleucel (JCAR017) as Second-Line Therapy in Adult Patients With Aggressive B-cell NHL (017006)
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Lymphoma, Non-Hodgkin, Lymphoma, Nonhodgkin, Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse
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* Biological: lisocabtagene maraleucel
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Inclusion Criteria:~Confirmation of relapsed or refractory aggressive B-cell non-Hodgkin lymphoma of the following histology at relapse: diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS; de novo or transformed follicular lymphoma [tFL]), high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (double/triple hit lymphoma [DHL/THL]), and follicular lymphoma Grade 3B per WHO 2016 classification~Previous treatment must include treatment with a single line of chemoimmunotherapy containing an anthracycline and a CD20-targeted agent~Subjects must be deemed ineligible for both high-dose chemotherapy and hematopoietic stem cell transplant (based on age, performance status and/or comorbidities) while also having adequate organ function for CAR T cell treatment.~Positron emission tomography (PET)-positive disease~Histological confirmation of diagnosis at last relapse. Enough tumor material must be available for central confirmation of diagnosis, otherwise a new tumor biopsy is mandated.~ECOG performance status of 0, or 1, or 2~Adequate vascular access for leukapheresis procedure (either peripheral line or surgically-placed line)~Subjects must agree to use appropriate contraception~Subjects must agree to not donate blood, organs, semen, and egg cells for usage in other individuals for at least 1 year following lymphodepleting chemotherapy~Exclusion Criteria:~Subjects with central nervous system (CNS)-only involvement by malignancy (note: subjects with secondary CNS involvement are allowed on study)~History of another primary malignancy that has not been in remission for at least 2 years.~Previous treatment with CD19-targeted therapy, with the exception of prior lisocabtagene maraleucel treatment in this protocol for subjects receiving retreatment~Active hepatitis B or hepatitis C infection at the time of screening~History of or active human immunodeficiency virus (HIV) infection at the time of screening~Uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate antibiotics or other treatment at the time of leukapheresis or lisocabtagene maraleucel administration~History of any one of the following cardiovascular conditions within the past 6 months: Class III or IV heart failure as defined by the New York Heart Association, cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac disease~History or presence of clinically relevant CNS pathology~Pregnant or nursing women~Subject does not meet protocol-specified washout periods for prior treatments~Prior hematopoietic stem cell transplant~Progressive vascular tumor invasion, thrombosis, or embolism~Venous thrombosis or embolism not managed on stable regimen of anticoagulation~Uncontrolled medical, psychological, familial, sociological, or geographical conditions
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18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | Overall response rate is the percent of participants with a best overall response (BOR) of either complete response (CR) or partial reasons (PR) based on the Independent Review Committee (IRC) assessment recorded from the time of JCAR017 treatment until disease progression, end of study, the start of another anticancer therapy or JCAR017 retreatment.~CR = Score 1, 2, or 3 with or without a residual mass on the positron emission tomography 5-point scale (PET 5PS). A score of 3 in many patients indicates a good prognosis with standard treatment.~PR = Score 4 or 5b with reduced uptake compared with baseline and residual mass(es) of any size.~PET 5PS = 1- no uptake above background; 2- uptake ≤ mediastinum; 3- uptake > mediastinum but ≤ liver; 4- uptake moderately > liver; 5- uptake markedly higher than liver and/or new lesions; X- new areas of uptake unlikely to be related to lymphoma. | From first dose to disease progression, end of study, the start of another anticancer therapy, or hematopoietic stem cell transplantation (up to approximately 24 months) |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Any Treatment-Emergent Adverse Events (TEAEs) | A TEAE was defined as an adverse event that started any time from initiation of product administration through and including 90 days following product administration. AEs that occurred after the initiation of subsequent anticancer therapy or product retreatment were not considered as product TEAE. AEs are graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (Version 4.03) (NCI CTCAE) guidelines where Grade 3= Severe, Grade 4= Life-threatening, and 5 = Death. | From first dose to 90 days following first dose (up to approximately 90 days) |
| Change From Baseline of Hematology Laboratory Results: Hemoglobin | Change from baseline in Hematology laboratory analysis. Includes Hemoglobin. Baseline is the last observation collected prior to or on the date of product infusion. | Baseline and Day 29 |
| Change From Baseline of Hematology Laboratory Results: Leukocytes, Lymphocytes, Neutrophils, Platelets | Change from baseline in Hematology laboratory analysis. Includes Leukocytes, Lymphocytes, Neutrophils, and Platelets. Baseline is the last observation collected prior to or on the date of product infusion. | Baseline and Day 29 |
| Change From Baseline of Chemistry Laboratory Results: Albumin | Change from baseline in Chemistry laboratory analysis. Includes Albumin. Baseline is the last observation collected prior to or on the date of product infusion. | Baseline and Day 29 |
| Change From Baseline of Chemistry Laboratory Results: Alanine Aminotransferase, Aspartate Aminotransferase, Lactate Dehydrogenase | Change from baseline in Chemistry laboratory analysis. Includes Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase. Baseline is the last observation collected prior to or on the date of product infusion. | Baseline and Day 29 |
| Change From Baseline of Chemistry Laboratory Results: Bilirubin, Creatinine, Direct Bilirubin, Urate | Change from baseline in Chemistry laboratory analysis. Includes Bilirubin, Creatinine, Direct Bilirubin, and Urate. Baseline is the last observation collected prior to or on the date of product infusion. | Baseline and Day 29 |
| Change From Baseline of Chemistry Laboratory Results: Calcium Corrected, Magnesium, Phosphate, Potassium, Sodium | Change from baseline in Chemistry laboratory analysis. Includes Calcium Corrected, Magnesium, Phosphate, Potassium, and Sodium. Baseline is the last observation collected prior to or on the date of product infusion. | Baseline and Day 29 |
| Complete Response (CR) Rate | Complete response rate (CRR) was defined as the percent of participants with a best overall response (BOR) of complete response (CR) based on the Independent Review Committee (IRC) assessment recorded from the time of JCAR017 treatment until disease progression, end of study, the start of another anticancer therapy or JCAR017 retreatment.~CR = Score 1, 2, or 3 with or without a residual mass on the positron emission tomography 5-point scale (PET 5PS). A score of 3 in many patients indicates a good prognosis with standard treatment.~PET 5PS = 1- no uptake above background; 2- uptake ≤ mediastinum; 3- uptake > mediastinum but ≤ liver; 4- uptake moderately > liver; 5- uptake markedly higher than liver and/or new lesions; X- new areas of uptake unlikely to be related to lymphoma. | From first dose to disease progression, end of study, the start of another anticancer therapy, or hematopoietic stem cell transplant (up to approximately 24 months) |
| Duration of Response (DOR) | Duration of response (DOR) is defined as the time from first complete response(CR) or partial response (PR) to progressive disease (PD) or death, whichever occurred first.~CR = Score 1, 2, or 3 on the positron emission tomography 5-point scale (PET 5PS). A score of 3 indicates a good prognosis with standard treatment.~PR = Score 4 or 5b with reduced uptake compared with baseline and residual mass(es) of any size.~PD = Score 4 or 5b on PET 5PS with an increase in intensity of uptake from baseline and/or new fluorodeoxyglucose-avid foci consistent with lymphoma at interim or end-of-treatment assessment.~PET 5PS = 1-no uptake above background; 2-uptake ≤ mediastinum; 3-uptake > mediastinum but ≤ liver; 4-uptake moderately > liver; 5-uptake markedly higher than liver and/or new lesions; X- new areas of uptake unlikely to be related to lymphoma. | From first dose to up to approximately 24 months |
| Duration of Response (DOR) in Participants With Complete Response (CR) | DOR for participants with a best overall response of CR was defined as the time from documentation of first response (or CR) to progressive disease (PD) or death, whichever occurred first. The first documentation of CR/PR is the latest of all dates of required measurements to establish the response. The progression date is the earliest date of all assessments that led to a response assessment of PD.~CR = Score 1, 2, or 3 on the positron emission tomography 5-point scale (PET 5PS). A score of 3 indicates a good prognosis with standard treatment.~PD = Score 4 or 5b on PET 5PS with an increase in intensity of uptake from baseline and/or new fluorodeoxyglucose-avid foci consistent with lymphoma at interim or end-of-treatment assessment.~PET 5PS = 1-no uptake above background; 2-uptake ≤ mediastinum; 3-uptake > mediastinum but ≤ liver; 4-uptake moderately > liver; 5-uptake markedly higher than liver and/or new lesions; X- new areas of uptake unlikely to be related to lymphoma. | From first dose to up to approximately 24 months |
| Progression-Free Survival (PFS) | PFS is defined as the time from JCAR017 infusion to progressive disease (PD) or death. Kaplan-Meier (KM) methodology will be used to analyze PFS.~PD = Score 4 or 5b on the positron emission tomography 5-point scale (PET 5PS) with an increase in intensity of uptake from baseline and/or new fluorodeoxyglucose-avid foci consistent with lymphoma at interim or end-of-treatment assessment.~PET 5PS = 1- no uptake above background; 2- uptake ≤ mediastinum; 3- uptake > mediastinum but ≤ liver; 4- uptake moderately > liver; 5- uptake markedly higher than liver and/or new lesions; X- new areas of uptake unlikely to be related to lymphoma. | From first dose to progressive disease (PD) or death (up to approximately 24 months) |
| Event-Free Survival (EFS) | EFS is defined as the time from JCAR017 infusion to the earliest of the following events: death from any cause, progressive disease (PD), or starting a new anticancer therapy. Kaplan-Meier (KM) methodology will be used to analyze EFS.~PD = Score 4 or 5b on PET 5PS with an increase in intensity of uptake from baseline and/or new fluorodeoxyglucose-avid foci consistent with lymphoma at interim or end-of-treatment assessment.~PET 5PS = 1-no uptake above background; 2-uptake ≤ mediastinum; 3-uptake > mediastinum but ≤ liver; 4-uptake moderately > liver; 5-uptake markedly higher than liver and/or new lesions; X- new areas of uptake unlikely to be related to lymphoma. | From first dose to death from any cause, progressive disease (PD), or starting a new anticancer therapy (up to approximately 24 months) |
| Overall Survival (OS) | OS is defined as the time from JCAR017 infusion to the date of death. Kaplan-Meier (KM) methodology will be used to analyze OS. | From first dose to date of death (up to approximately 24 months) |
| PK Parameters of JCAR017 in Blood as Assessed by qPCR: Cmax | Pharmacokinetic (PK) analyses were based on quantitative polymerase chain reaction (qPCR).~Cmax = Maximum observed blood concentration. | From first dose to up to 24 months |
| PK Parameters of JCAR017 in Blood as Assessed by qPCR: Tmax | Pharmacokinetic (PK) analyses were based on quantitative polymerase chain reaction (qPCR). Tmax = Time of maximum observed blood concentration. | From first dose to up to 24 months |
| PK Parameters of JCAR017 in Blood as Assessed by qPCR: AUC (0-28) | Pharmacokinetic (PK) analyses were based on quantitative polymerase chain reaction (qPCR). AUC (0-28) = Area under the curve for concentration. | From first dose to up to 24 months |
| Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Fatigue Subscale | Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire.~The EORTC QLQ-C30 is a 30-item scale composed of both multi-item scales and single-item measures.~All of the scales and single-item measures range in score from 0 to 100. A 10-point change in the scoring is considered to be a meaningful change in HRQoL.~Symptom scale/item higher score represents a high level of symptomatic problem. | Baseline and Day 29 |
| Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Physical Functioning Subscale | Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire.~The EORTC QLQ-C30 is a 30-item scale composed of both multi-item scales and single-item measures.~All of the scales and single-item measures range in score from 0 to 100. A 10-point change in the scoring is considered to be a meaningful change in HRQoL.~Functional scale and global health status/HRQoL higher scale score represents a higher level of well-being and better ability of daily functioning. | Baseline and Day 29 |
| Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Cognitive Functioning Subscale | Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire.~The EORTC QLQ-C30 is a 30-item scale composed of both multi-item scales and single-item measures.~All of the scales and single-item measures range in score from 0 to 100. A 10-point change in the scoring is considered to be a meaningful change in HRQoL.~Functional scale and global health status/HRQoL higher scale score represents a higher level of well-being and better ability of daily functioning. | Baseline and Day 29 |
| Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Global Health/QoL Subscale | Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire.~The EORTC QLQ-C30 is a 30-item scale composed of both multi-item scales and single-item measures.~All of the scales and single-item measures range in score from 0 to 100. A 10-point change in the scoring is considered to be a meaningful change in HRQoL.~Functional scale and global health status/HRQoL higher scale score represents a higher level of well-being and better ability of daily functioning. | Baseline and Day 29 |
| Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Role Functioning Subscale | Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire.~The EORTC QLQ-C30 is a 30-item scale composed of both multi-item scales and single-item measures.~All of the scales and single-item measures range in score from 0 to 100. A 10-point change in the scoring is considered to be a meaningful change in HRQoL.~Functional scale and global health status/HRQoL higher scale score represents a higher level of well-being and better ability of daily functioning. | Baseline and Day 29 |
| Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Emotional Functioning Subscale | Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire.~The EORTC QLQ-C30 is a 30-item scale composed of both multi-item scales and single-item measures.~All of the scales and single-item measures range in score from 0 to 100. A 10-point change in the scoring is considered to be a meaningful change in HRQoL.~Functional scale and global health status/HRQoL higher scale score represents a higher level of well-being and better ability of daily functioning. | Baseline and Day 29 |
| Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Social Functioning Subscale | Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire.~The EORTC QLQ-C30 is a 30-item scale composed of both multi-item scales and single-item measures.~All of the scales and single-item measures range in score from 0 to 100. A 10-point change in the scoring is considered to be a meaningful change in HRQoL.~Functional scale and global health status/HRQoL higher scale score represents a higher level of well-being and better ability of daily functioning. | Baseline and Day 29 |
| Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Pain Subscale | Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire.~The EORTC QLQ-C30 is a 30-item scale composed of both multi-item scales and single-item measures.~All of the scales and single-item measures range in score from 0 to 100. A 10-point change in the scoring is considered to be a meaningful change in HRQoL.~Symptom scale/item higher score represents a high level of symptomatic problem. | Baseline and Day 29 |
| Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Nausea/Vomiting Subscale | Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire.~The EORTC QLQ-C30 is a 30-item scale composed of both multi-item scales and single-item measures.~All of the scales and single-item measures range in score from 0 to 100. A 10-point change in the scoring is considered to be a meaningful change in HRQoL.~Symptom scale/item higher score represents a high level of symptomatic problem. | Baseline and Day 29 |
| Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Constipation Subscale | Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire.~The EORTC QLQ-C30 is a 30-item scale composed of both multi-item scales and single-item measures.~All of the scales and single-item measures range in score from 0 to 100. A 10-point change in the scoring is considered to be a meaningful change in HRQoL.~Symptom scale/item higher score represents a high level of symptomatic problem. | Baseline and Day 29 |
| Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Diarrhea Subscale | Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire.~The EORTC QLQ-C30 is a 30-item scale composed of both multi-item scales and single-item measures.~All of the scales and single-item measures range in score from 0 to 100. A 10-point change in the scoring is considered to be a meaningful change in HRQoL.~Symptom scale/item higher score represents a high level of symptomatic problem. | Baseline and Day 29 |
| Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Insomnia Subscale | Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire.~The EORTC QLQ-C30 is a 30-item scale composed of both multi-item scales and single-item measures.~All of the scales and single-item measures range in score from 0 to 100. A 10-point change in the scoring is considered to be a meaningful change in HRQoL.~Symptom scale/item higher score represents a high level of symptomatic problem. | Baseline and Day 29 |
| Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Dyspnea Subscale | Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire.~The EORTC QLQ-C30 is a 30-item scale composed of both multi-item scales and single-item measures.~All of the scales and single-item measures range in score from 0 to 100. A 10-point change in the scoring is considered to be a meaningful change in HRQoL.~Symptom scale/item higher score represents a high level of symptomatic problem. | Baseline and Day 29 |
| Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Appetite Loss Subscale | Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire.~The EORTC QLQ-C30 is a 30-item scale composed of both multi-item scales and single-item measures.~All of the scales and single-item measures range in score from 0 to 100. A 10-point change in the scoring is considered to be a meaningful change in HRQoL.~Symptom scale/item higher score represents a high level of symptomatic problem. | Baseline and Day 29 |
| Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Financial Difficulties Subscale | Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire.~The EORTC QLQ-C30 is a 30-item scale composed of both multi-item scales and single-item measures.~All of the scales and single-item measures range in score from 0 to 100. A 10-point change in the scoring is considered to be a meaningful change in HRQoL.~Functional scale and global health status/HRQoL higher scale score represents a higher level of well-being and better ability of daily functioning. | Baseline and Day 29 |
| Health-Related Quality of Life (HRQoL) Assessed by the FACT-Lym Subscale | The Functional Assessment of Cancer Treatment-Lymphoma (FACT-Lym) consists of the FACT-General scale and a 15-item lymphoma-specific additional concerns subscale (LYM). This scale addresses symptoms and functional limitations that are important to lymphoma patients. The LYM items are scored on a 0 (Not at all) to 4 (Very much) response scale. Items are aggregated to a single score on a 0-60 scale. | Baseline and Day 29 |
| Health-Related Quality of Life (HRQoL) Assessed by the EuroQol Instrument EQ-5D-5L | The European Quality of Life 5D-5L Scale (EQ-5D-5L) assesses general health-related quality of life. Health is defined in 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Responses are coded so that a '1' indicates no problem, and '5' indicates the most serious problem. The responses for the 5 dimensions are combined in a 5-digit number. These health states are converted to a single index value using the crosswalk method to the EQ-5D-3L value set from the United Kingdom (UK). The EQ-5D-5L health states ranged from -.594 for the worst (55555) to 1 for the best (11111) for UK value set with an optimal health state is assigned a score of 1.00, death is assigned a score of 0.00 and negative values representing values as worse than dead. A change of .08 is considered to be a clinically meaningful change in health utility. | Baseline and Day 29 |
| Numbers of Intensive Care Unit (ICU) Inpatient Days | The numbers of ICU inpatient days. | From first dose after JCAR017 infusion to up to approximately 24 months |
| Numbers of Non-intensive Care Unit (ICU) Inpatient Days | Number of non-ICU inpatient days. | From first dose after JCAR017 infusion to up to approximately 24 months |
| The Number of Participants That Were Hospitalized For Adverse Events, Prophylaxis, Other | Length of hospitalization stay was reported for up to 24 months post liso-cel infusion. Reasons for hospitalization include adverse events, prophylaxis, and other. Adverse events were reported for up to 90 days post liso-cel infusion. | From first dose after JCAR017 infusion to up to approximately 24 months |
|
JCAR017, lisocabtagene maraleucel, NHL, chimeric antigen receptor, CAR, CAR T cell, autologous T cell therapy, immunotherapy, cell therapy, liso-cel
|
Lymphoma, Lymphoma, Non-Hodgkin, Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, Neoplasms by Histologic Type, Neoplasms, Lymphoproliferative Disorders, Lymphatic Diseases, Immunoproliferative Disorders, Immune System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Lisocabtagene maraleucel at a dose of 100×10^6 CAR+ T cells (50×10^6 CD8+ CAR+ T cells and 50×10^6 CD4+ CAR+ T cells), will be given IV in a single-dose schedule on Day 1 (between 2 and 7 days following the completion of lymphodepleting chemotherapy). | Biological: lisocabtagene maraleucel<br>* lisocabtagene maraleucel will be administered as a single dose intravenous (IV) injection<br>* Other names: liso-cel;|
|
Lisocabtagene Maraleucel (JCAR017) as Second-Line Therapy (TRANSCEND-PILOT-017006)
Study Overview
=================
Brief Summary
-----------------
This is a Phase 2, open-label, multicenter study to determine the efficacy and safety of lisocabtagene maraleucel (JCAR017) in adult subjects who have relapsed from, or are refractory to, a single line of immunochemotherapy for aggressive B-cell non-Hodgkin lymphoma (NHL) and are ineligible for hematopoietic stem cell transplant (based on age, performance status, and/or comorbidities). Subjects will receive treatment with lisocabtagene maraleucel and will be followed for 2 years for safety, pharmacokinetics and biomarkers, disease status, quality of life, and survival.
Official Title
-----------------
A Phase 2 Study of Lisocabtagene Maraleucel (JCAR017) as Second-Line Therapy in Adult Patients With Aggressive B-cell NHL (017006)
Conditions
-----------------
Lymphoma, Non-Hodgkin, Lymphoma, Nonhodgkin, Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse
Intervention / Treatment
-----------------
* Biological: lisocabtagene maraleucel
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Confirmation of relapsed or refractory aggressive B-cell non-Hodgkin lymphoma of the following histology at relapse: diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS; de novo or transformed follicular lymphoma [tFL]), high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (double/triple hit lymphoma [DHL/THL]), and follicular lymphoma Grade 3B per WHO 2016 classification Previous treatment must include treatment with a single line of chemoimmunotherapy containing an anthracycline and a CD20-targeted agent Subjects must be deemed ineligible for both high-dose chemotherapy and hematopoietic stem cell transplant (based on age, performance status and/or comorbidities) while also having adequate organ function for CAR T cell treatment. Positron emission tomography (PET)-positive disease Histological confirmation of diagnosis at last relapse. Enough tumor material must be available for central confirmation of diagnosis, otherwise a new tumor biopsy is mandated. ECOG performance status of 0, or 1, or 2 Adequate vascular access for leukapheresis procedure (either peripheral line or surgically-placed line) Subjects must agree to use appropriate contraception Subjects must agree to not donate blood, organs, semen, and egg cells for usage in other individuals for at least 1 year following lymphodepleting chemotherapy Exclusion Criteria: Subjects with central nervous system (CNS)-only involvement by malignancy (note: subjects with secondary CNS involvement are allowed on study) History of another primary malignancy that has not been in remission for at least 2 years. Previous treatment with CD19-targeted therapy, with the exception of prior lisocabtagene maraleucel treatment in this protocol for subjects receiving retreatment Active hepatitis B or hepatitis C infection at the time of screening History of or active human immunodeficiency virus (HIV) infection at the time of screening Uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate antibiotics or other treatment at the time of leukapheresis or lisocabtagene maraleucel administration History of any one of the following cardiovascular conditions within the past 6 months: Class III or IV heart failure as defined by the New York Heart Association, cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac disease History or presence of clinically relevant CNS pathology Pregnant or nursing women Subject does not meet protocol-specified washout periods for prior treatments Prior hematopoietic stem cell transplant Progressive vascular tumor invasion, thrombosis, or embolism Venous thrombosis or embolism not managed on stable regimen of anticoagulation Uncontrolled medical, psychological, familial, sociological, or geographical conditions
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
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All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Lisocabtagene maraleucel at a dose of 100×10^6 CAR+ T cells (50×10^6 CD8+ CAR+ T cells and 50×10^6 CD4+ CAR+ T cells), will be given IV in a single-dose schedule on Day 1 (between 2 and 7 days following the completion of lymphodepleting chemotherapy). | Biological: lisocabtagene maraleucel<br>* lisocabtagene maraleucel will be administered as a single dose intravenous (IV) injection<br>* Other names: liso-cel;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | Overall response rate is the percent of participants with a best overall response (BOR) of either complete response (CR) or partial reasons (PR) based on the Independent Review Committee (IRC) assessment recorded from the time of JCAR017 treatment until disease progression, end of study, the start of another anticancer therapy or JCAR017 retreatment. CR = Score 1, 2, or 3 with or without a residual mass on the positron emission tomography 5-point scale (PET 5PS). A score of 3 in many patients indicates a good prognosis with standard treatment. PR = Score 4 or 5b with reduced uptake compared with baseline and residual mass(es) of any size. PET 5PS = 1- no uptake above background; 2- uptake ≤ mediastinum; 3- uptake > mediastinum but ≤ liver; 4- uptake moderately > liver; 5- uptake markedly higher than liver and/or new lesions; X- new areas of uptake unlikely to be related to lymphoma. | From first dose to disease progression, end of study, the start of another anticancer therapy, or hematopoietic stem cell transplantation (up to approximately 24 months) |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Any Treatment-Emergent Adverse Events (TEAEs) | A TEAE was defined as an adverse event that started any time from initiation of product administration through and including 90 days following product administration. AEs that occurred after the initiation of subsequent anticancer therapy or product retreatment were not considered as product TEAE. AEs are graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (Version 4.03) (NCI CTCAE) guidelines where Grade 3= Severe, Grade 4= Life-threatening, and 5 = Death. | From first dose to 90 days following first dose (up to approximately 90 days) |
| Change From Baseline of Hematology Laboratory Results: Hemoglobin | Change from baseline in Hematology laboratory analysis. Includes Hemoglobin. Baseline is the last observation collected prior to or on the date of product infusion. | Baseline and Day 29 |
| Change From Baseline of Hematology Laboratory Results: Leukocytes, Lymphocytes, Neutrophils, Platelets | Change from baseline in Hematology laboratory analysis. Includes Leukocytes, Lymphocytes, Neutrophils, and Platelets. Baseline is the last observation collected prior to or on the date of product infusion. | Baseline and Day 29 |
| Change From Baseline of Chemistry Laboratory Results: Albumin | Change from baseline in Chemistry laboratory analysis. Includes Albumin. Baseline is the last observation collected prior to or on the date of product infusion. | Baseline and Day 29 |
| Change From Baseline of Chemistry Laboratory Results: Alanine Aminotransferase, Aspartate Aminotransferase, Lactate Dehydrogenase | Change from baseline in Chemistry laboratory analysis. Includes Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase. Baseline is the last observation collected prior to or on the date of product infusion. | Baseline and Day 29 |
| Change From Baseline of Chemistry Laboratory Results: Bilirubin, Creatinine, Direct Bilirubin, Urate | Change from baseline in Chemistry laboratory analysis. Includes Bilirubin, Creatinine, Direct Bilirubin, and Urate. Baseline is the last observation collected prior to or on the date of product infusion. | Baseline and Day 29 |
| Change From Baseline of Chemistry Laboratory Results: Calcium Corrected, Magnesium, Phosphate, Potassium, Sodium | Change from baseline in Chemistry laboratory analysis. Includes Calcium Corrected, Magnesium, Phosphate, Potassium, and Sodium. Baseline is the last observation collected prior to or on the date of product infusion. | Baseline and Day 29 |
| Complete Response (CR) Rate | Complete response rate (CRR) was defined as the percent of participants with a best overall response (BOR) of complete response (CR) based on the Independent Review Committee (IRC) assessment recorded from the time of JCAR017 treatment until disease progression, end of study, the start of another anticancer therapy or JCAR017 retreatment. CR = Score 1, 2, or 3 with or without a residual mass on the positron emission tomography 5-point scale (PET 5PS). A score of 3 in many patients indicates a good prognosis with standard treatment. PET 5PS = 1- no uptake above background; 2- uptake ≤ mediastinum; 3- uptake > mediastinum but ≤ liver; 4- uptake moderately > liver; 5- uptake markedly higher than liver and/or new lesions; X- new areas of uptake unlikely to be related to lymphoma. | From first dose to disease progression, end of study, the start of another anticancer therapy, or hematopoietic stem cell transplant (up to approximately 24 months) |
| Duration of Response (DOR) | Duration of response (DOR) is defined as the time from first complete response(CR) or partial response (PR) to progressive disease (PD) or death, whichever occurred first. CR = Score 1, 2, or 3 on the positron emission tomography 5-point scale (PET 5PS). A score of 3 indicates a good prognosis with standard treatment. PR = Score 4 or 5b with reduced uptake compared with baseline and residual mass(es) of any size. PD = Score 4 or 5b on PET 5PS with an increase in intensity of uptake from baseline and/or new fluorodeoxyglucose-avid foci consistent with lymphoma at interim or end-of-treatment assessment. PET 5PS = 1-no uptake above background; 2-uptake ≤ mediastinum; 3-uptake > mediastinum but ≤ liver; 4-uptake moderately > liver; 5-uptake markedly higher than liver and/or new lesions; X- new areas of uptake unlikely to be related to lymphoma. | From first dose to up to approximately 24 months |
| Duration of Response (DOR) in Participants With Complete Response (CR) | DOR for participants with a best overall response of CR was defined as the time from documentation of first response (or CR) to progressive disease (PD) or death, whichever occurred first. The first documentation of CR/PR is the latest of all dates of required measurements to establish the response. The progression date is the earliest date of all assessments that led to a response assessment of PD. CR = Score 1, 2, or 3 on the positron emission tomography 5-point scale (PET 5PS). A score of 3 indicates a good prognosis with standard treatment. PD = Score 4 or 5b on PET 5PS with an increase in intensity of uptake from baseline and/or new fluorodeoxyglucose-avid foci consistent with lymphoma at interim or end-of-treatment assessment. PET 5PS = 1-no uptake above background; 2-uptake ≤ mediastinum; 3-uptake > mediastinum but ≤ liver; 4-uptake moderately > liver; 5-uptake markedly higher than liver and/or new lesions; X- new areas of uptake unlikely to be related to lymphoma. | From first dose to up to approximately 24 months |
| Progression-Free Survival (PFS) | PFS is defined as the time from JCAR017 infusion to progressive disease (PD) or death. Kaplan-Meier (KM) methodology will be used to analyze PFS. PD = Score 4 or 5b on the positron emission tomography 5-point scale (PET 5PS) with an increase in intensity of uptake from baseline and/or new fluorodeoxyglucose-avid foci consistent with lymphoma at interim or end-of-treatment assessment. PET 5PS = 1- no uptake above background; 2- uptake ≤ mediastinum; 3- uptake > mediastinum but ≤ liver; 4- uptake moderately > liver; 5- uptake markedly higher than liver and/or new lesions; X- new areas of uptake unlikely to be related to lymphoma. | From first dose to progressive disease (PD) or death (up to approximately 24 months) |
| Event-Free Survival (EFS) | EFS is defined as the time from JCAR017 infusion to the earliest of the following events: death from any cause, progressive disease (PD), or starting a new anticancer therapy. Kaplan-Meier (KM) methodology will be used to analyze EFS. PD = Score 4 or 5b on PET 5PS with an increase in intensity of uptake from baseline and/or new fluorodeoxyglucose-avid foci consistent with lymphoma at interim or end-of-treatment assessment. PET 5PS = 1-no uptake above background; 2-uptake ≤ mediastinum; 3-uptake > mediastinum but ≤ liver; 4-uptake moderately > liver; 5-uptake markedly higher than liver and/or new lesions; X- new areas of uptake unlikely to be related to lymphoma. | From first dose to death from any cause, progressive disease (PD), or starting a new anticancer therapy (up to approximately 24 months) |
| Overall Survival (OS) | OS is defined as the time from JCAR017 infusion to the date of death. Kaplan-Meier (KM) methodology will be used to analyze OS. | From first dose to date of death (up to approximately 24 months) |
| PK Parameters of JCAR017 in Blood as Assessed by qPCR: Cmax | Pharmacokinetic (PK) analyses were based on quantitative polymerase chain reaction (qPCR). Cmax = Maximum observed blood concentration. | From first dose to up to 24 months |
| PK Parameters of JCAR017 in Blood as Assessed by qPCR: Tmax | Pharmacokinetic (PK) analyses were based on quantitative polymerase chain reaction (qPCR). Tmax = Time of maximum observed blood concentration. | From first dose to up to 24 months |
| PK Parameters of JCAR017 in Blood as Assessed by qPCR: AUC (0-28) | Pharmacokinetic (PK) analyses were based on quantitative polymerase chain reaction (qPCR). AUC (0-28) = Area under the curve for concentration. | From first dose to up to 24 months |
| Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Fatigue Subscale | Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. The EORTC QLQ-C30 is a 30-item scale composed of both multi-item scales and single-item measures. All of the scales and single-item measures range in score from 0 to 100. A 10-point change in the scoring is considered to be a meaningful change in HRQoL. Symptom scale/item higher score represents a high level of symptomatic problem. | Baseline and Day 29 |
| Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Physical Functioning Subscale | Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. The EORTC QLQ-C30 is a 30-item scale composed of both multi-item scales and single-item measures. All of the scales and single-item measures range in score from 0 to 100. A 10-point change in the scoring is considered to be a meaningful change in HRQoL. Functional scale and global health status/HRQoL higher scale score represents a higher level of well-being and better ability of daily functioning. | Baseline and Day 29 |
| Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Cognitive Functioning Subscale | Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. The EORTC QLQ-C30 is a 30-item scale composed of both multi-item scales and single-item measures. All of the scales and single-item measures range in score from 0 to 100. A 10-point change in the scoring is considered to be a meaningful change in HRQoL. Functional scale and global health status/HRQoL higher scale score represents a higher level of well-being and better ability of daily functioning. | Baseline and Day 29 |
| Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Global Health/QoL Subscale | Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. The EORTC QLQ-C30 is a 30-item scale composed of both multi-item scales and single-item measures. All of the scales and single-item measures range in score from 0 to 100. A 10-point change in the scoring is considered to be a meaningful change in HRQoL. Functional scale and global health status/HRQoL higher scale score represents a higher level of well-being and better ability of daily functioning. | Baseline and Day 29 |
| Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Role Functioning Subscale | Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. The EORTC QLQ-C30 is a 30-item scale composed of both multi-item scales and single-item measures. All of the scales and single-item measures range in score from 0 to 100. A 10-point change in the scoring is considered to be a meaningful change in HRQoL. Functional scale and global health status/HRQoL higher scale score represents a higher level of well-being and better ability of daily functioning. | Baseline and Day 29 |
| Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Emotional Functioning Subscale | Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. The EORTC QLQ-C30 is a 30-item scale composed of both multi-item scales and single-item measures. All of the scales and single-item measures range in score from 0 to 100. A 10-point change in the scoring is considered to be a meaningful change in HRQoL. Functional scale and global health status/HRQoL higher scale score represents a higher level of well-being and better ability of daily functioning. | Baseline and Day 29 |
| Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Social Functioning Subscale | Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. The EORTC QLQ-C30 is a 30-item scale composed of both multi-item scales and single-item measures. All of the scales and single-item measures range in score from 0 to 100. A 10-point change in the scoring is considered to be a meaningful change in HRQoL. Functional scale and global health status/HRQoL higher scale score represents a higher level of well-being and better ability of daily functioning. | Baseline and Day 29 |
| Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Pain Subscale | Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. The EORTC QLQ-C30 is a 30-item scale composed of both multi-item scales and single-item measures. All of the scales and single-item measures range in score from 0 to 100. A 10-point change in the scoring is considered to be a meaningful change in HRQoL. Symptom scale/item higher score represents a high level of symptomatic problem. | Baseline and Day 29 |
| Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Nausea/Vomiting Subscale | Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. The EORTC QLQ-C30 is a 30-item scale composed of both multi-item scales and single-item measures. All of the scales and single-item measures range in score from 0 to 100. A 10-point change in the scoring is considered to be a meaningful change in HRQoL. Symptom scale/item higher score represents a high level of symptomatic problem. | Baseline and Day 29 |
| Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Constipation Subscale | Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. The EORTC QLQ-C30 is a 30-item scale composed of both multi-item scales and single-item measures. All of the scales and single-item measures range in score from 0 to 100. A 10-point change in the scoring is considered to be a meaningful change in HRQoL. Symptom scale/item higher score represents a high level of symptomatic problem. | Baseline and Day 29 |
| Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Diarrhea Subscale | Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. The EORTC QLQ-C30 is a 30-item scale composed of both multi-item scales and single-item measures. All of the scales and single-item measures range in score from 0 to 100. A 10-point change in the scoring is considered to be a meaningful change in HRQoL. Symptom scale/item higher score represents a high level of symptomatic problem. | Baseline and Day 29 |
| Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Insomnia Subscale | Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. The EORTC QLQ-C30 is a 30-item scale composed of both multi-item scales and single-item measures. All of the scales and single-item measures range in score from 0 to 100. A 10-point change in the scoring is considered to be a meaningful change in HRQoL. Symptom scale/item higher score represents a high level of symptomatic problem. | Baseline and Day 29 |
| Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Dyspnea Subscale | Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. The EORTC QLQ-C30 is a 30-item scale composed of both multi-item scales and single-item measures. All of the scales and single-item measures range in score from 0 to 100. A 10-point change in the scoring is considered to be a meaningful change in HRQoL. Symptom scale/item higher score represents a high level of symptomatic problem. | Baseline and Day 29 |
| Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Appetite Loss Subscale | Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. The EORTC QLQ-C30 is a 30-item scale composed of both multi-item scales and single-item measures. All of the scales and single-item measures range in score from 0 to 100. A 10-point change in the scoring is considered to be a meaningful change in HRQoL. Symptom scale/item higher score represents a high level of symptomatic problem. | Baseline and Day 29 |
| Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Financial Difficulties Subscale | Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. The EORTC QLQ-C30 is a 30-item scale composed of both multi-item scales and single-item measures. All of the scales and single-item measures range in score from 0 to 100. A 10-point change in the scoring is considered to be a meaningful change in HRQoL. Functional scale and global health status/HRQoL higher scale score represents a higher level of well-being and better ability of daily functioning. | Baseline and Day 29 |
| Health-Related Quality of Life (HRQoL) Assessed by the FACT-Lym Subscale | The Functional Assessment of Cancer Treatment-Lymphoma (FACT-Lym) consists of the FACT-General scale and a 15-item lymphoma-specific additional concerns subscale (LYM). This scale addresses symptoms and functional limitations that are important to lymphoma patients. The LYM items are scored on a 0 (Not at all) to 4 (Very much) response scale. Items are aggregated to a single score on a 0-60 scale. | Baseline and Day 29 |
| Health-Related Quality of Life (HRQoL) Assessed by the EuroQol Instrument EQ-5D-5L | The European Quality of Life 5D-5L Scale (EQ-5D-5L) assesses general health-related quality of life. Health is defined in 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Responses are coded so that a '1' indicates no problem, and '5' indicates the most serious problem. The responses for the 5 dimensions are combined in a 5-digit number. These health states are converted to a single index value using the crosswalk method to the EQ-5D-3L value set from the United Kingdom (UK). The EQ-5D-5L health states ranged from -.594 for the worst (55555) to 1 for the best (11111) for UK value set with an optimal health state is assigned a score of 1.00, death is assigned a score of 0.00 and negative values representing values as worse than dead. A change of .08 is considered to be a clinically meaningful change in health utility. | Baseline and Day 29 |
| Numbers of Intensive Care Unit (ICU) Inpatient Days | The numbers of ICU inpatient days. | From first dose after JCAR017 infusion to up to approximately 24 months |
| Numbers of Non-intensive Care Unit (ICU) Inpatient Days | Number of non-ICU inpatient days. | From first dose after JCAR017 infusion to up to approximately 24 months |
| The Number of Participants That Were Hospitalized For Adverse Events, Prophylaxis, Other | Length of hospitalization stay was reported for up to 24 months post liso-cel infusion. Reasons for hospitalization include adverse events, prophylaxis, and other. Adverse events were reported for up to 90 days post liso-cel infusion. | From first dose after JCAR017 infusion to up to approximately 24 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
JCAR017, lisocabtagene maraleucel, NHL, chimeric antigen receptor, CAR, CAR T cell, autologous T cell therapy, immunotherapy, cell therapy, liso-cel
|
|
NCT02643706
|
Relationship Between ALDH2 and CIN
|
The purpose of this clinical trial is to investigate the relationship between the gene polymorphism of aldehyde dehydrogenase 2 and contrast induced nephropathy and its mechanism.
|
Patients undergoing coronary angiography or percutaneous coronary intervention will be recruited in this study after they sign the informed consent.5ml venous blood was extracted from the peripheral vein before the operation to detect the renal function, the genotype and enzyme activity of aldehyde dehydrogenase 2 ,and the levels of oxidative stress and inflammation.Another 5ml venous blood was extracted from the peripheral vein 24-72 hours after the operation to detect the renal function and the levels of oxidative stress and inflammation.Activated oxygen protein products , 4-HNE and hs-CRP as markers for oxidative stress and inflammation.The renal function index contains serum creatinine，urea nitrogen and cystatin C.
|
Relationship Between the Gene Polymorphism of Aldehyde Dehydrogenase 2 and Contrast Induced Nephropathy
|
Radiographic Contrast Agent Nephropathy
|
Inclusion Criteria:~Patients undergoing elective coronary intervention or coronary angiography at Yu Qilu hospital.~All the patients or their guardians must sign the consent form before entering the trial.~Exclusion Criteria:~Patients with acute renal failure, renal transplantation, end-stage renal disease, or dialysis treatment, GFR < 15ml/min.~Use of renal toxicity drugs during the treatment, such as non steroidal anti-inflammatory drugs, etc.~Patients who has used contrast agent 10 days before the operation.~Cardiac shock, hypotension (systolic blood pressure < 95mmHg),or hyper- tension with difficulty to control.~Allergy to contrast media.~Congestive heart failure (left ventricular ejection fraction<40%), cardiac function NYHA grade IV.~Pregnancy or lactation.
|
18 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with different ALDH2 genotype | | 1-30 days after samples collected |
| Change from baseline renal function after the operation | The baseline of renal function will be tested at the next morning after admission .The renal function will be tested again 24-72 hours after coronary angiography or coronary intervention.The changes of renal function will be recorded.The renal function index contains serum creatinine,urea nitrogen and cystatin C. | at admission and 24-72hours after coronary angiography or coronary intervention |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aldehyde dehydrogenase 2 activity | | 1-30 days after samples collected |
| Activated oxygen protein products, 4-HNE and hs-CRP | Activated oxygen protein products , 4-HNE and hs-CRP as markers for oxidative stress and inflammation. | 1-30 days after samples collected |
|
Aldehyde dehydrogenase 2, contrast induced nephropathy, Gene polymorphism
|
Kidney Diseases, Urologic Diseases, Female Urogenital Diseases, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases, Male Urogenital Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CIN<br>CIN was defined as an absolute increase in serum creatinine concentration of at least 0.5 mg/dL (44.2umol/l) or a relative rise of at least 25% from baseline on the follow-up blood sample drawn 24 to 72 hours after the operation. | |
| Control<br>The enrolled patients without CIN. | |
|
Relationship Between ALDH2 and CIN
Study Overview
=================
Brief Summary
-----------------
The purpose of this clinical trial is to investigate the relationship between the gene polymorphism of aldehyde dehydrogenase 2 and contrast induced nephropathy and its mechanism.
Detailed Description
-----------------
Patients undergoing coronary angiography or percutaneous coronary intervention will be recruited in this study after they sign the informed consent.5ml venous blood was extracted from the peripheral vein before the operation to detect the renal function, the genotype and enzyme activity of aldehyde dehydrogenase 2 ,and the levels of oxidative stress and inflammation.Another 5ml venous blood was extracted from the peripheral vein 24-72 hours after the operation to detect the renal function and the levels of oxidative stress and inflammation.Activated oxygen protein products , 4-HNE and hs-CRP as markers for oxidative stress and inflammation.The renal function index contains serum creatinine，urea nitrogen and cystatin C.
Official Title
-----------------
Relationship Between the Gene Polymorphism of Aldehyde Dehydrogenase 2 and Contrast Induced Nephropathy
Conditions
-----------------
Radiographic Contrast Agent Nephropathy
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients undergoing elective coronary intervention or coronary angiography at Yu Qilu hospital. All the patients or their guardians must sign the consent form before entering the trial. Exclusion Criteria: Patients with acute renal failure, renal transplantation, end-stage renal disease, or dialysis treatment, GFR < 15ml/min. Use of renal toxicity drugs during the treatment, such as non steroidal anti-inflammatory drugs, etc. Patients who has used contrast agent 10 days before the operation. Cardiac shock, hypotension (systolic blood pressure < 95mmHg),or hyper- tension with difficulty to control. Allergy to contrast media. Congestive heart failure (left ventricular ejection fraction<40%), cardiac function NYHA grade IV. Pregnancy or lactation.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CIN<br>CIN was defined as an absolute increase in serum creatinine concentration of at least 0.5 mg/dL (44.2umol/l) or a relative rise of at least 25% from baseline on the follow-up blood sample drawn 24 to 72 hours after the operation. | |
| Control<br>The enrolled patients without CIN. | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with different ALDH2 genotype | | 1-30 days after samples collected |
| Change from baseline renal function after the operation | The baseline of renal function will be tested at the next morning after admission .The renal function will be tested again 24-72 hours after coronary angiography or coronary intervention.The changes of renal function will be recorded.The renal function index contains serum creatinine,urea nitrogen and cystatin C. | at admission and 24-72hours after coronary angiography or coronary intervention |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aldehyde dehydrogenase 2 activity | | 1-30 days after samples collected |
| Activated oxygen protein products, 4-HNE and hs-CRP | Activated oxygen protein products , 4-HNE and hs-CRP as markers for oxidative stress and inflammation. | 1-30 days after samples collected |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Aldehyde dehydrogenase 2, contrast induced nephropathy, Gene polymorphism
|
||
NCT01990534
|
A Study of Brentuximab Vedotin in Participants With Relapsed or Refractory Hodgkin Lymphoma
|
This phase 4, single-arm, open-label, multicenter study is designed to evaluate the efficacy and safety of brentuximab vedotin as a single agent in adult participants with histologically confirmed CD30+ relapsed or refractory classical Hodgkin Lymphoma who have not received a prior stem cell transplantation (SCT) and are considered to be not suitable for SCT or multiagent chemotherapy at the time of study entry.
|
The drug being tested in this study is called brentuximab vedotin. Brentuximab vedotin is being tested to treat people who have relapsed or refractory Hodgkin Lymphoma. This study will look at the overall response of people who took brentuximab vedotin.~The study will enroll 60 patients. Participants received:~• Brentuximab vedotin 1.8 mg/kg~This multicenter trial is being conducted worldwide. The overall time to participate in this study is approximately 6 to 7 years. Participants will make multiple visits to the clinic, and will be contacted by telephone every 3 months for 18 months after the end of treatment (EOT) for follow-up assessment of overall survival and then every 6 months until death, study closure, or 5 years after enrollment of the last participant.
|
A Single-arm Study of Brentuximab Vedotin in Patients With Relapsed or Refractory Hodgkin Lymphoma Who Are Not Suitable for Stem Cell Transplantation or Multiagent Chemotherapy
|
Hodgkin Lymphoma
|
* Drug: Brentuximab Vedotin
|
Inclusion Criteria:~Each participant must meet all of the following inclusion criteria to be enrolled in the study:~Male or female participants 18 years or older, with relapsed or refractory classical Hodgkin lymphoma (HL), who have previously received at least 1 prior systemic chemotherapeutic regimen~Not suitable for stem cell transplantation (SCT) or multiagent chemotherapy, according to 1 of the following criteria:~Disease progression within 90 days of the earliest date of complete remission (CR) or complete remission unconfirmed (CRu) after the end of treatment with multiagent chemotherapeutic regimens and/or radiotherapy~Progressive disease during frontline multiagent chemotherapy~Disease relapse after treatment with at least 2 chemotherapeutic regimens, including any salvage treatments~Bidimensional measurable disease~An Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1~Female participants who are postmenopausal for at least 1 year before the screening visit, surgically sterile, or agree to practice 2 effective methods of contraception at the same time, or agree to practice true abstinence.~Male participants who agree to practice effective barrier contraception during the entire study treatment period through 6 months after the last dose of study drug or agree to practice true abstinence.~Clinical laboratory values as specified in the study protocol.~Exclusion Criteria:~Participants who meet any of the following exclusion criteria are not to be enrolled in the study:~Previous treatment with brentuximab vedotin~Previously received an autologous stem cell transplantation (ASCT) or alloSCT~Known cerebral/meningeal disease, including signs or symptoms suggestive of progressive multifocal leukoencephalopathy (PML), or any history of PML.~Female participants who are lactating and breastfeeding or pregnant.~Known human immunodeficiency virus (HIV).~Known hepatitis B surface antigen positive, or known or suspected active hepatitis C infection.~Grade 2 or higher peripheral neuropathy.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Objective response rate is defined as the percentage of participants with complete remission (CR) or partial remission (PR) as assessed by an independent review facility (IRF) using International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma. CR is defined as the disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites. | Baseline until disease progression, death or end of study (EOS) (Up to 24 months) |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DOR) | DOR is defined as the time in months from the date of first documentation of a CR or PR response to the date of first documentation of tumor progression or progressive disease (PD) per IRF assessment according to IWG criteria. CR is defined as the disappearance of all evidence of disease. PR is defined as regression of measurable disease and no new sites. PD is defined as any new lesion or increase by >50% of previously involved sites from nadir. | From first documented complete or partial remission until disease progression (Up to 24 months) |
| Progression Free Survival (PFS) | PFS is defined as time in months from start of study treatment to first documentation of objective tumor progression per IRF assessment or up to death due to any cause, whichever occurs first. | Baseline until disease progression, death or end of treatment (EOT), and then every 3 months up to approximately 6 years |
| Complete Remission Rate | Complete remission rate is defined as percentage of participants with CR per IRF response assessment based on IWG criteria are reported. CR is defined as the disappearance of all evidence of disease. | Baseline until disease progression, death or EOS (Up to approximately 6 years) |
| Duration of Complete Remission | Duration of CR is defined as the time from the date of first documentation of a CR or to the date of first documentation of tumor progression or progressive disease (PD) per IRF assessment according to IWG criteria. CR is defined as the disappearance of all evidence of disease and PD is defined as any new lesion or increase by >50% of previously involved sites from nadir. | From first documented complete remission until disease progression (up to approximately 6 years) |
| Overall Survival (OS) | OS is the time in months from start of study treatment to date of death due to any cause. | Every 3 months for 18 months after EOT, thereafter, every 6 months until the sooner of death, study closure, or 5 years after enrollment of the last participant (up to approximately 6 years) |
| Percentage of Participants Who Received Hematopoietic SCT | | Baseline up to EOS (up to approximately 6 years) |
| Number of Participants With Adverse Events (AEs), Drug-Related AEs, Grade 3 or Higher AEs, Serious Adverse Events (SAEs), Drug-Related SAEs and Grade 3 or Higher SAEs | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A SAE a serious is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. AE severity was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. AEs Grade 3 and higher are severe. | From first dose through 30 days after the last dose of study medication (Up to 24 months) |
| Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs | Abnormal clinical laboratory values (serum chemistry and hematology) were reported as AEs if they were considered by the investigator to be a clinically significant change from Baseline or led to premature discontinuation of study treatment, dose modification, or other therapeutic intervention. | From the first dose through 30 days after the last dose of study medication (Up to 24 months) |
| Antibody-drug Conjugate (ADC) Serum Concentrations | Blood samples were collected and tested for serum concentrations of brentuximab vedotin antibody-drug conjugate. | Cycle 1 pre-dose and 10 minutes, 24 hours and 336 hours post-dose; Cycle 2 pre-dose and 10 minutes post-dose; Cycle 3 pre-dose and 10 minutes, 24 hours and 336 hours post-dose; Cycle 4 to 16 pre-dose and 10 minutes post-dose; EOT (Up to 24 months) |
| Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Blood samples were collected and tested for conjugated and unconjugated antibodies. | Cycle 1 pre-dose and 10 minutes, 24 hours and 336 hours post-dose; Cycle 2 pre-dose and 10 minutes post-dose; Cycle 3 pre-dose and 10 minutes, 24 hours and 336 hours post-dose; Cycle 4 to 16 pre-dose and 10 minutes post-dose; EOT (Up to 24 months) |
| Monomethyl Auristatin E (MMAE) Serum Concentrations | Blood samples were collected and tested for MMAE serum concentrations. | Cycle 1 pre-dose and 10 minutes, 24 hours and 336 hours post-dose; Cycle 2 pre-dose and 10 minutes post-dose; Cycle 3 pre-dose and 10 minutes, 24 hours and 336 hours post-dose; Cycle 4 to 16 pre-dose and 10 minutes post-dose; EOT (Up to 24 months) |
| Number of Participants With Antitherapeutic Antibodies (ATA) | Blood samples were collected to assess the immunogenicity of brentuximab vedotin (ATA development) using a laboratory test. Confirmed ATA-positive response was categorized as transient (defined as 1 or 2 post-Baseline confirmed ATA-positive responses) and persistent (defined as more than 2 post-Baseline confirmed ATA positive responses) and neutralizing ATA (nATA) status. The confirmed ATA-positive samples were assessed for ATA titer and delineated into having high or low titers. | Day 1 of every 3-week cycle up to 16 cycles and EOT (Up to 24 months) |
|
Immunoproliferative Disorders, Immune System Diseases, Lymphoma, Hodgkin, Relapsed, Refractory, Antigens, CD30, Antibody-Drug Conjugate, Antibodies, Monoclonal, Monomethyl auristatin E, Drug Therapy, Immunotherapy, Hematologic Diseases, Additional Relevant MeSH terms:, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Hodgkin, Neoplasms by Histologic Type, Neoplasms, Lymphoproliferative Disorders, Lymphatic Diseases, Lymphoma, B-Cell, Lymphoma, T-Cell, Immunologic Factors, Physiological Effects of Drugs, Pharmacologic Actions
|
Antineoplastic Agents, Immunological, Brentuximab Vedotin, Antineoplastic Agents, Immunotoxins, Immunoconjugates, Immunologic Factors, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brentuximab Vedotin 1.8 mg/kg<br>Brentuximab vedotin 1.8 mg/kg, 30-minute intravenous (IV) infusion, Day 1 in every 3-week cycle, until there is evidence of disease progression or unacceptable toxicity occurs (Up to 16 cycles). The dose could be decreased or delayed or discontinued in participants who develop treatment-associated non-hematologic, hematologic toxicity or peripheral neuropathy to brentuximab vedotin. | Drug: Brentuximab Vedotin<br>* Brentuximab vedotin IV infusion<br>* Other names: ADCETRIS;|
|
A Study of Brentuximab Vedotin in Participants With Relapsed or Refractory Hodgkin Lymphoma
Study Overview
=================
Brief Summary
-----------------
This phase 4, single-arm, open-label, multicenter study is designed to evaluate the efficacy and safety of brentuximab vedotin as a single agent in adult participants with histologically confirmed CD30+ relapsed or refractory classical Hodgkin Lymphoma who have not received a prior stem cell transplantation (SCT) and are considered to be not suitable for SCT or multiagent chemotherapy at the time of study entry.
Detailed Description
-----------------
The drug being tested in this study is called brentuximab vedotin. Brentuximab vedotin is being tested to treat people who have relapsed or refractory Hodgkin Lymphoma. This study will look at the overall response of people who took brentuximab vedotin. The study will enroll 60 patients. Participants received: • Brentuximab vedotin 1.8 mg/kg This multicenter trial is being conducted worldwide. The overall time to participate in this study is approximately 6 to 7 years. Participants will make multiple visits to the clinic, and will be contacted by telephone every 3 months for 18 months after the end of treatment (EOT) for follow-up assessment of overall survival and then every 6 months until death, study closure, or 5 years after enrollment of the last participant.
Official Title
-----------------
A Single-arm Study of Brentuximab Vedotin in Patients With Relapsed or Refractory Hodgkin Lymphoma Who Are Not Suitable for Stem Cell Transplantation or Multiagent Chemotherapy
Conditions
-----------------
Hodgkin Lymphoma
Intervention / Treatment
-----------------
* Drug: Brentuximab Vedotin
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Each participant must meet all of the following inclusion criteria to be enrolled in the study: Male or female participants 18 years or older, with relapsed or refractory classical Hodgkin lymphoma (HL), who have previously received at least 1 prior systemic chemotherapeutic regimen Not suitable for stem cell transplantation (SCT) or multiagent chemotherapy, according to 1 of the following criteria: Disease progression within 90 days of the earliest date of complete remission (CR) or complete remission unconfirmed (CRu) after the end of treatment with multiagent chemotherapeutic regimens and/or radiotherapy Progressive disease during frontline multiagent chemotherapy Disease relapse after treatment with at least 2 chemotherapeutic regimens, including any salvage treatments Bidimensional measurable disease An Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 Female participants who are postmenopausal for at least 1 year before the screening visit, surgically sterile, or agree to practice 2 effective methods of contraception at the same time, or agree to practice true abstinence. Male participants who agree to practice effective barrier contraception during the entire study treatment period through 6 months after the last dose of study drug or agree to practice true abstinence. Clinical laboratory values as specified in the study protocol. Exclusion Criteria: Participants who meet any of the following exclusion criteria are not to be enrolled in the study: Previous treatment with brentuximab vedotin Previously received an autologous stem cell transplantation (ASCT) or alloSCT Known cerebral/meningeal disease, including signs or symptoms suggestive of progressive multifocal leukoencephalopathy (PML), or any history of PML. Female participants who are lactating and breastfeeding or pregnant. Known human immunodeficiency virus (HIV). Known hepatitis B surface antigen positive, or known or suspected active hepatitis C infection. Grade 2 or higher peripheral neuropathy.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brentuximab Vedotin 1.8 mg/kg<br>Brentuximab vedotin 1.8 mg/kg, 30-minute intravenous (IV) infusion, Day 1 in every 3-week cycle, until there is evidence of disease progression or unacceptable toxicity occurs (Up to 16 cycles). The dose could be decreased or delayed or discontinued in participants who develop treatment-associated non-hematologic, hematologic toxicity or peripheral neuropathy to brentuximab vedotin. | Drug: Brentuximab Vedotin<br>* Brentuximab vedotin IV infusion<br>* Other names: ADCETRIS;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Objective response rate is defined as the percentage of participants with complete remission (CR) or partial remission (PR) as assessed by an independent review facility (IRF) using International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma. CR is defined as the disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites. | Baseline until disease progression, death or end of study (EOS) (Up to 24 months) |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DOR) | DOR is defined as the time in months from the date of first documentation of a CR or PR response to the date of first documentation of tumor progression or progressive disease (PD) per IRF assessment according to IWG criteria. CR is defined as the disappearance of all evidence of disease. PR is defined as regression of measurable disease and no new sites. PD is defined as any new lesion or increase by >50% of previously involved sites from nadir. | From first documented complete or partial remission until disease progression (Up to 24 months) |
| Progression Free Survival (PFS) | PFS is defined as time in months from start of study treatment to first documentation of objective tumor progression per IRF assessment or up to death due to any cause, whichever occurs first. | Baseline until disease progression, death or end of treatment (EOT), and then every 3 months up to approximately 6 years |
| Complete Remission Rate | Complete remission rate is defined as percentage of participants with CR per IRF response assessment based on IWG criteria are reported. CR is defined as the disappearance of all evidence of disease. | Baseline until disease progression, death or EOS (Up to approximately 6 years) |
| Duration of Complete Remission | Duration of CR is defined as the time from the date of first documentation of a CR or to the date of first documentation of tumor progression or progressive disease (PD) per IRF assessment according to IWG criteria. CR is defined as the disappearance of all evidence of disease and PD is defined as any new lesion or increase by >50% of previously involved sites from nadir. | From first documented complete remission until disease progression (up to approximately 6 years) |
| Overall Survival (OS) | OS is the time in months from start of study treatment to date of death due to any cause. | Every 3 months for 18 months after EOT, thereafter, every 6 months until the sooner of death, study closure, or 5 years after enrollment of the last participant (up to approximately 6 years) |
| Percentage of Participants Who Received Hematopoietic SCT | | Baseline up to EOS (up to approximately 6 years) |
| Number of Participants With Adverse Events (AEs), Drug-Related AEs, Grade 3 or Higher AEs, Serious Adverse Events (SAEs), Drug-Related SAEs and Grade 3 or Higher SAEs | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A SAE a serious is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. AE severity was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. AEs Grade 3 and higher are severe. | From first dose through 30 days after the last dose of study medication (Up to 24 months) |
| Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs | Abnormal clinical laboratory values (serum chemistry and hematology) were reported as AEs if they were considered by the investigator to be a clinically significant change from Baseline or led to premature discontinuation of study treatment, dose modification, or other therapeutic intervention. | From the first dose through 30 days after the last dose of study medication (Up to 24 months) |
| Antibody-drug Conjugate (ADC) Serum Concentrations | Blood samples were collected and tested for serum concentrations of brentuximab vedotin antibody-drug conjugate. | Cycle 1 pre-dose and 10 minutes, 24 hours and 336 hours post-dose; Cycle 2 pre-dose and 10 minutes post-dose; Cycle 3 pre-dose and 10 minutes, 24 hours and 336 hours post-dose; Cycle 4 to 16 pre-dose and 10 minutes post-dose; EOT (Up to 24 months) |
| Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Blood samples were collected and tested for conjugated and unconjugated antibodies. | Cycle 1 pre-dose and 10 minutes, 24 hours and 336 hours post-dose; Cycle 2 pre-dose and 10 minutes post-dose; Cycle 3 pre-dose and 10 minutes, 24 hours and 336 hours post-dose; Cycle 4 to 16 pre-dose and 10 minutes post-dose; EOT (Up to 24 months) |
| Monomethyl Auristatin E (MMAE) Serum Concentrations | Blood samples were collected and tested for MMAE serum concentrations. | Cycle 1 pre-dose and 10 minutes, 24 hours and 336 hours post-dose; Cycle 2 pre-dose and 10 minutes post-dose; Cycle 3 pre-dose and 10 minutes, 24 hours and 336 hours post-dose; Cycle 4 to 16 pre-dose and 10 minutes post-dose; EOT (Up to 24 months) |
| Number of Participants With Antitherapeutic Antibodies (ATA) | Blood samples were collected to assess the immunogenicity of brentuximab vedotin (ATA development) using a laboratory test. Confirmed ATA-positive response was categorized as transient (defined as 1 or 2 post-Baseline confirmed ATA-positive responses) and persistent (defined as more than 2 post-Baseline confirmed ATA positive responses) and neutralizing ATA (nATA) status. The confirmed ATA-positive samples were assessed for ATA titer and delineated into having high or low titers. | Day 1 of every 3-week cycle up to 16 cycles and EOT (Up to 24 months) |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Immunoproliferative Disorders, Immune System Diseases, Lymphoma, Hodgkin, Relapsed, Refractory, Antigens, CD30, Antibody-Drug Conjugate, Antibodies, Monoclonal, Monomethyl auristatin E, Drug Therapy, Immunotherapy, Hematologic Diseases, Additional Relevant MeSH terms:, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Hodgkin, Neoplasms by Histologic Type, Neoplasms, Lymphoproliferative Disorders, Lymphatic Diseases, Lymphoma, B-Cell, Lymphoma, T-Cell, Immunologic Factors, Physiological Effects of Drugs, Pharmacologic Actions
|
NCT02337478
|
Vincristine Sulfate Liposome in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
|
This pilot phase II trial studies how well vincristine sulfate liposome works in treating patients with acute myeloid leukemia that has returned after a period of improvement or has not responded to previous treatment. Drugs used in chemotherapy, such as vincristine sulfate liposome, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Liposomal encapsulation prolongs bioavailability (proportion of drug that enters the circulation when introduced into the body) of vincristine sulfate, and may increase its delivery to cancer cells with fewer side effects.
|
PRIMARY OBJECTIVES:~I. To determine the feasibility of administering vincristine sulfate liposome injection (VSLI) to relapsed or refractory acute myeloid leukemia (AML) patients having failed, refused or not a candidate for at least one chemotherapy salvage regimen.~II. To observe the hematologic improvement-rate of VSLI in this patient population.~SECONDARY OBJECTIVES:~I. To observe the overall survival of patients treated with VSLI. II. To observe the response rate (complete remission [CR], complete remission with incomplete count recovery [CRi], partial response [PR], and morphologic leukemia free state [MLFS]) of VSLI in this patient population.~OUTLINE:~Patients receive vincristine sulfate liposome via injection on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.~After completion of study treatment, patients are followed up for up to 6 months.
|
An Open Label, Phase II Study of the Feasibility and Efficacy of Vincristine Sulfate Liposome Injection in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)
|
Recurrent Adult Acute Myeloid Leukemia
|
* Drug: Vincristine Sulfate Liposome
* Other: Laboratory Biomarker Analysis
|
Inclusion Criteria:~Patients must have histologically or cytologically documented relapsed and/or refractory acute myeloid leukemia~Patients must be ineligible for, refused or having failed at least one previous salvage regimen~Eastern Cooperative Oncology Group (ECOG) performance status of =< 3~Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use accepted contraceptive methods (abstinence, intrauterine device [IUD], oral contraceptive or double barrier device), and must have a negative serum or urine pregnancy test within 1 week prior to treatment initiation~Fertile men must practice effective contraceptive methods during the study period, unless documentation of infertility exists~Mentally competent, ability to understand and willingness to sign the informed consent form~No serious medical illness that would potentially increase patients' risk for toxicity~No active central nervous system (CNS) disease~No active uncontrolled bleeding/bleeding diathesis~No condition or abnormality which may, in the opinion of the investigator, compromise the safety of the patient~No unwillingness or inability to follow protocol requirements~No evidence of ongoing, uncontrolled infection~No requirement for immediate palliative treatment of any kind including surgery~No option for immediate bone marrow transplant unless patient refuses this therapy~Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) =< 3 x upper normal limit (UNL), alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) =< 3 x UNL~Bilirubin =< 3 x UNL~Glomerular filtration rate (GFR) > 50 ml/min/1.72 m^2 or creatinine < 2 g/dL~Exclusion Criteria:~Serious medical illness or severe debilitating pulmonary disease that would potentially increase the patients' risk for toxicity~Patients with persistent grade 3 or higher prior vincristine (VCR) (vincristine sulfate)-related neuropathy~Patients with active central nervous system (CNS) disease~Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease)~Pregnant women, or women of child-bearing potential not using reliable means of contraception~Lactating females~Fertile men unwilling to practice contraceptive methods during the study period~Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of patients~Unwilling or unable to follow protocol requirements~Evidence of ongoing, uncontrolled infection~Patients with known human immunodeficiency virus (HIV) infection~Requirement for immediate palliative treatment of any kind including surgery~Evidence of inadequate hepatic function (aspartate aminotransferase [AST/SGOT] =< 3 x upper normal limit [UNL], alanine aminotransferase [ALT/SGPT] =< 3 x UNL [=< 5 x ULN if liver metastases present], bilirubin =< 1.5 x UNL)~Evidence of inadequate renal function (creatinine > 2 g/dL)
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Able to Complete Two or More Courses of Therapy Regardless of Dose Modifications | | Up to 56 days |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate (CR, CRi, PR, and MLFS) | Confidence intervals will be calculated around the estimates of the response rate (CR, CRi, PR, and MLFS) of VSLI. Assuming a response rate of 0.1, with 39 participants, 95 percent confidence intervals with a 0.09 margin of error (0.01, 0.19) or a margin of error of 0.16 around a response rate of 0.5 will be created.~(Complete remission (CR) bone marrow blasts <5%, absence of blasts with Auer rods; absence of extramedullary disease, absolute neutrophil count >1,000, platelet count >100,000, independence of red cell transfusions; Complete remission with incomplete recovery (CRi) all complete remission except for residual neutropenia or thrombocytopenia; partial remission (PR), decrease of bone marrow blast to 5-25%, decrease of pre-treatment bone marrow blast by at least 50%; morphologic leukemia-free state (MLFS) Bone marrow blasts <5%, absence of Aeur rods, absence of extramedullary disease, no hematologic recovery required). | Up to 6 months after completion of study treatment |
| Overall Survival | Kaplan-Meier estimation will be used to analyze overall survival. | Up to 6 months after completion of therapy |
|
Antimitotic Agents, Mitosis Modulators, Molecular Mechanisms of Pharmacological Action, Vincristine, Antineoplastic Agents, Phytogenic, Antineoplastic Agents, Tubulin Modulators
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (vincristine sulfate liposome)<br>Patients receive vincristine sulfate liposome via injection on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Drug: Vincristine Sulfate Liposome<br>* Given via injection<br>* Other names: vincristine sulfate liposome injection;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>|
|
Vincristine Sulfate Liposome in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
Study Overview
=================
Brief Summary
-----------------
This pilot phase II trial studies how well vincristine sulfate liposome works in treating patients with acute myeloid leukemia that has returned after a period of improvement or has not responded to previous treatment. Drugs used in chemotherapy, such as vincristine sulfate liposome, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Liposomal encapsulation prolongs bioavailability (proportion of drug that enters the circulation when introduced into the body) of vincristine sulfate, and may increase its delivery to cancer cells with fewer side effects.
Detailed Description
-----------------
PRIMARY OBJECTIVES: I. To determine the feasibility of administering vincristine sulfate liposome injection (VSLI) to relapsed or refractory acute myeloid leukemia (AML) patients having failed, refused or not a candidate for at least one chemotherapy salvage regimen. II. To observe the hematologic improvement-rate of VSLI in this patient population. SECONDARY OBJECTIVES: I. To observe the overall survival of patients treated with VSLI. II. To observe the response rate (complete remission [CR], complete remission with incomplete count recovery [CRi], partial response [PR], and morphologic leukemia free state [MLFS]) of VSLI in this patient population. OUTLINE: Patients receive vincristine sulfate liposome via injection on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for up to 6 months.
Official Title
-----------------
An Open Label, Phase II Study of the Feasibility and Efficacy of Vincristine Sulfate Liposome Injection in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)
Conditions
-----------------
Recurrent Adult Acute Myeloid Leukemia
Intervention / Treatment
-----------------
* Drug: Vincristine Sulfate Liposome
* Other: Laboratory Biomarker Analysis
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients must have histologically or cytologically documented relapsed and/or refractory acute myeloid leukemia Patients must be ineligible for, refused or having failed at least one previous salvage regimen Eastern Cooperative Oncology Group (ECOG) performance status of =< 3 Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use accepted contraceptive methods (abstinence, intrauterine device [IUD], oral contraceptive or double barrier device), and must have a negative serum or urine pregnancy test within 1 week prior to treatment initiation Fertile men must practice effective contraceptive methods during the study period, unless documentation of infertility exists Mentally competent, ability to understand and willingness to sign the informed consent form No serious medical illness that would potentially increase patients' risk for toxicity No active central nervous system (CNS) disease No active uncontrolled bleeding/bleeding diathesis No condition or abnormality which may, in the opinion of the investigator, compromise the safety of the patient No unwillingness or inability to follow protocol requirements No evidence of ongoing, uncontrolled infection No requirement for immediate palliative treatment of any kind including surgery No option for immediate bone marrow transplant unless patient refuses this therapy Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) =< 3 x upper normal limit (UNL), alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) =< 3 x UNL Bilirubin =< 3 x UNL Glomerular filtration rate (GFR) > 50 ml/min/1.72 m^2 or creatinine < 2 g/dL Exclusion Criteria: Serious medical illness or severe debilitating pulmonary disease that would potentially increase the patients' risk for toxicity Patients with persistent grade 3 or higher prior vincristine (VCR) (vincristine sulfate)-related neuropathy Patients with active central nervous system (CNS) disease Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease) Pregnant women, or women of child-bearing potential not using reliable means of contraception Lactating females Fertile men unwilling to practice contraceptive methods during the study period Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of patients Unwilling or unable to follow protocol requirements Evidence of ongoing, uncontrolled infection Patients with known human immunodeficiency virus (HIV) infection Requirement for immediate palliative treatment of any kind including surgery Evidence of inadequate hepatic function (aspartate aminotransferase [AST/SGOT] =< 3 x upper normal limit [UNL], alanine aminotransferase [ALT/SGPT] =< 3 x UNL [=< 5 x ULN if liver metastases present], bilirubin =< 1.5 x UNL) Evidence of inadequate renal function (creatinine > 2 g/dL)
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (vincristine sulfate liposome)<br>Patients receive vincristine sulfate liposome via injection on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Drug: Vincristine Sulfate Liposome<br>* Given via injection<br>* Other names: vincristine sulfate liposome injection;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Able to Complete Two or More Courses of Therapy Regardless of Dose Modifications | | Up to 56 days |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate (CR, CRi, PR, and MLFS) | Confidence intervals will be calculated around the estimates of the response rate (CR, CRi, PR, and MLFS) of VSLI. Assuming a response rate of 0.1, with 39 participants, 95 percent confidence intervals with a 0.09 margin of error (0.01, 0.19) or a margin of error of 0.16 around a response rate of 0.5 will be created. (Complete remission (CR) bone marrow blasts <5%, absence of blasts with Auer rods; absence of extramedullary disease, absolute neutrophil count >1,000, platelet count >100,000, independence of red cell transfusions; Complete remission with incomplete recovery (CRi) all complete remission except for residual neutropenia or thrombocytopenia; partial remission (PR), decrease of bone marrow blast to 5-25%, decrease of pre-treatment bone marrow blast by at least 50%; morphologic leukemia-free state (MLFS) Bone marrow blasts <5%, absence of Aeur rods, absence of extramedullary disease, no hematologic recovery required). | Up to 6 months after completion of study treatment |
| Overall Survival | Kaplan-Meier estimation will be used to analyze overall survival. | Up to 6 months after completion of therapy |
|
|
NCT05310617
|
Parental Project and Premature Ovarian Insufficiency
|
One of the main repercussions of POI is infertility. When the diagnosis of POI is announced, the question of fertility is addressed and the patient is often directed towards egg donation or adoption when she has a parental project. However, there are cases of spontaneous pregnancies after diagnosis.~This study was conducted to determine the proportion of patients with POI who were able to realize a parental project after diagnosis in the long term and by what means.
|
The investigators propose to study patients with POI who were hospitalized in the endocrinology and reproductive medicine department of the Pitié-Salpêtrière Hospital for the etiological assessment of ovarian failure and its consequences between December 31, 1982 and January 12, 2021. The investigators will only include patients who were admitted to the day hospital because we have a complete etiological workup and a complete history for them, which allows investigators to describe the population properly. The patients must be over 18 years old at the time of the survey in order to be able to evaluate the presence of a parental project only in adult patients.~Patients for whom there is no valid contact information in the computer file (postal address or valid email address or cell phone number) or whose last consultation was more than 2 years ago will be excluded. Patients with Turner syndrome will be excluded because they may have comorbidities, particularly cardiac, that contraindicate pregnancy. Patients with POI secondary to oncological treatments (gonadotoxic chemotherapy or pelvic radiotherapy) will also be excluded because of the uncertain prognosis and the contraindications to pregnancy in case of hormone-dependent tumors.
|
Parental Project and Premature Ovarian Insufficiency
|
Infertility, Primary Ovarian Insufficiency
|
* Other: Survey
|
Inclusion Criteria:~Patients at least 18 years old at the time of the survey~Patients with a diagnosis of PIO according to the current definition: cycle disturbances of more than 4 months and FSH > 25 on 2 measurements one month apart~Patients having been hospitalized in day hospital (HDJ) in the endocrinology and reproductive medicine department of the Pitié-Salpêtrière hospital for the etiological assessment of ovarian insufficiency and its repercussions between December 31, 1982 and January 12, 2021~Valid contact information available: address, cell phone, e-mail~Patients who have been informed and do not object to participate in the study~Exclusion Criteria:~Turner syndrome~POI secondary to oncology treatments (chemotherapy, pelvic radiotherapy)~Opposition to participating in the study
|
18 Years
| null |
Female
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Realisation of parental project | Determine proportion of patient who realised a parental project after the diagnosis of POI | data from patients with a diagnosis between 31/12/1982 and 12/01/2021 and whose opposition to the study is not expressed |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine how and to what extent they have carried out their parental project | Evaluation if, after the diagnosis of POI, the parental project was realized through: spontaneous pregnancy or egg donation, simple stimulation or in vitro fertilization, embryo reception, or the adoption of a child after the diagnosis of POI | data from patients with a diagnosis between 31/12/1982 and 12/01/2021 and whose opposition to the study is not expressed |
| determine how many children on average these patients had after the diagnosis of POI. | Evaluation of the number of children born after the diagnosis of POI | data from patients with a diagnosis between 31/12/1982 and 12/01/2021 and whose opposition to the study is not expressed |
| determine the delay between the diagnosis of POI and the birth of the first child after the diagnosis according to the method | Evaluation of the time between the diagnosis of POI and the birth of the first child after diagnosis according to the method (egg donation, spontaneous pregnancy, adoption, etc.) | data from patients with a diagnosis between 31/12/1982 and 12/01/2021 and whose opposition to the study is not expressed |
| Survey. Describe the characteristics of patients who were able to have a child after diagnosis | Evaluation of the characteristics of patients who were able to have a child after diagnosis:~o age at diagnosis | data from patients with a diagnosis between 31/12/1982 and 12/01/2021 and whose opposition to the study is not expressed |
| Survey. Describe the characteristics of patients who were able to have a child after diagnosis | Evaluation of the characteristics of patients who were able to have a child after diagnosis:~o AMH level | data from patients with a diagnosis between 31/12/1982 and 12/01/2021 and whose opposition to the study is not expressed |
| Survey. Describe the characteristics of patients who were able to have a child after diagnosis | Evaluation of the characteristics of patients who were able to have a child after diagnosis:~o FSH level | data from patients with a diagnosis between 31/12/1982 and 12/01/2021 and whose opposition to the study is not expressed |
| Survey. Describe the characteristics of patients who were able to have a child after diagnosis | Evaluation of the characteristics of patients who were able to have a child after diagnosis:~o presence of follicles on ultrasound | data from patients with a diagnosis between 31/12/1982 and 12/01/2021 and whose opposition to the study is not expressed |
| Survey. Describe the characteristics of patients who were able to have a child after diagnosis | Evaluation of the characteristics of patients who were able to have a child after diagnosis:~o cause of POI | data from patients with a diagnosis between 31/12/1982 and 12/01/2021 and whose opposition to the study is not expressed |
| Survey. Describe the characteristics of patients who were able to have a child after diagnosis | Evaluation of the characteristics of patients who were able to have a child after diagnosis:~o number of pregnancies prior to diagnosis | data from patients with a diagnosis between 31/12/1982 and 12/01/2021 and whose opposition to the study is not expressed |
| Survey. Describe the characteristics of patients who were able to have a child after diagnosis | Evaluation of the characteristics of patients who were able to have a child after diagnosis:~o number of children before diagnosis | data from patients with a diagnosis between 31/12/1982 and 12/01/2021 and whose opposition to the study is not expressed |
| Survey. Describe the characteristics of patients who were able to have a child after diagnosis | Evaluation of the characteristics of patients who were able to have a child after diagnosis:~o normal puberty | data from patients with a diagnosis between 31/12/1982 and 12/01/2021 and whose opposition to the study is not expressed |
| Survey. Describe the characteristics of patients who were able to have a child after diagnosis | Evaluation of the characteristics of patients who were able to have a child after diagnosis:~o age at menarche | data from patients with a diagnosis between 31/12/1982 and 12/01/2021 and whose opposition to the study is not expressed |
|
spontaneous pregnancy, adoption, oocyte donation, parental project
|
Infertility, Menopause, Premature, Primary Ovarian Insufficiency, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases, Genital Diseases, Ovarian Diseases, Adnexal Diseases, Genital Diseases, Female, Female Urogenital Diseases, Gonadal Disorders, Endocrine System Diseases
|
| Intervention/Treatment |
| --- |
|Other: Survey|Survey on the parental project and its realisation|
|
Parental Project and Premature Ovarian Insufficiency
Study Overview
=================
Brief Summary
-----------------
One of the main repercussions of POI is infertility. When the diagnosis of POI is announced, the question of fertility is addressed and the patient is often directed towards egg donation or adoption when she has a parental project. However, there are cases of spontaneous pregnancies after diagnosis. This study was conducted to determine the proportion of patients with POI who were able to realize a parental project after diagnosis in the long term and by what means.
Detailed Description
-----------------
The investigators propose to study patients with POI who were hospitalized in the endocrinology and reproductive medicine department of the Pitié-Salpêtrière Hospital for the etiological assessment of ovarian failure and its consequences between December 31, 1982 and January 12, 2021. The investigators will only include patients who were admitted to the day hospital because we have a complete etiological workup and a complete history for them, which allows investigators to describe the population properly. The patients must be over 18 years old at the time of the survey in order to be able to evaluate the presence of a parental project only in adult patients. Patients for whom there is no valid contact information in the computer file (postal address or valid email address or cell phone number) or whose last consultation was more than 2 years ago will be excluded. Patients with Turner syndrome will be excluded because they may have comorbidities, particularly cardiac, that contraindicate pregnancy. Patients with POI secondary to oncological treatments (gonadotoxic chemotherapy or pelvic radiotherapy) will also be excluded because of the uncertain prognosis and the contraindications to pregnancy in case of hormone-dependent tumors.
Official Title
-----------------
Parental Project and Premature Ovarian Insufficiency
Conditions
-----------------
Infertility, Primary Ovarian Insufficiency
Intervention / Treatment
-----------------
* Other: Survey
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients at least 18 years old at the time of the survey Patients with a diagnosis of PIO according to the current definition: cycle disturbances of more than 4 months and FSH > 25 on 2 measurements one month apart Patients having been hospitalized in day hospital (HDJ) in the endocrinology and reproductive medicine department of the Pitié-Salpêtrière hospital for the etiological assessment of ovarian insufficiency and its repercussions between December 31, 1982 and January 12, 2021 Valid contact information available: address, cell phone, e-mail Patients who have been informed and do not object to participate in the study Exclusion Criteria: Turner syndrome POI secondary to oncology treatments (chemotherapy, pelvic radiotherapy) Opposition to participating in the study
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
Female
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Intervention/Treatment |
| --- |
|Other: Survey|Survey on the parental project and its realisation|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Realisation of parental project | Determine proportion of patient who realised a parental project after the diagnosis of POI | data from patients with a diagnosis between 31/12/1982 and 12/01/2021 and whose opposition to the study is not expressed |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine how and to what extent they have carried out their parental project | Evaluation if, after the diagnosis of POI, the parental project was realized through: spontaneous pregnancy or egg donation, simple stimulation or in vitro fertilization, embryo reception, or the adoption of a child after the diagnosis of POI | data from patients with a diagnosis between 31/12/1982 and 12/01/2021 and whose opposition to the study is not expressed |
| determine how many children on average these patients had after the diagnosis of POI. | Evaluation of the number of children born after the diagnosis of POI | data from patients with a diagnosis between 31/12/1982 and 12/01/2021 and whose opposition to the study is not expressed |
| determine the delay between the diagnosis of POI and the birth of the first child after the diagnosis according to the method | Evaluation of the time between the diagnosis of POI and the birth of the first child after diagnosis according to the method (egg donation, spontaneous pregnancy, adoption, etc.) | data from patients with a diagnosis between 31/12/1982 and 12/01/2021 and whose opposition to the study is not expressed |
| Survey. Describe the characteristics of patients who were able to have a child after diagnosis | Evaluation of the characteristics of patients who were able to have a child after diagnosis: o age at diagnosis | data from patients with a diagnosis between 31/12/1982 and 12/01/2021 and whose opposition to the study is not expressed |
| Survey. Describe the characteristics of patients who were able to have a child after diagnosis | Evaluation of the characteristics of patients who were able to have a child after diagnosis: o AMH level | data from patients with a diagnosis between 31/12/1982 and 12/01/2021 and whose opposition to the study is not expressed |
| Survey. Describe the characteristics of patients who were able to have a child after diagnosis | Evaluation of the characteristics of patients who were able to have a child after diagnosis: o FSH level | data from patients with a diagnosis between 31/12/1982 and 12/01/2021 and whose opposition to the study is not expressed |
| Survey. Describe the characteristics of patients who were able to have a child after diagnosis | Evaluation of the characteristics of patients who were able to have a child after diagnosis: o presence of follicles on ultrasound | data from patients with a diagnosis between 31/12/1982 and 12/01/2021 and whose opposition to the study is not expressed |
| Survey. Describe the characteristics of patients who were able to have a child after diagnosis | Evaluation of the characteristics of patients who were able to have a child after diagnosis: o cause of POI | data from patients with a diagnosis between 31/12/1982 and 12/01/2021 and whose opposition to the study is not expressed |
| Survey. Describe the characteristics of patients who were able to have a child after diagnosis | Evaluation of the characteristics of patients who were able to have a child after diagnosis: o number of pregnancies prior to diagnosis | data from patients with a diagnosis between 31/12/1982 and 12/01/2021 and whose opposition to the study is not expressed |
| Survey. Describe the characteristics of patients who were able to have a child after diagnosis | Evaluation of the characteristics of patients who were able to have a child after diagnosis: o number of children before diagnosis | data from patients with a diagnosis between 31/12/1982 and 12/01/2021 and whose opposition to the study is not expressed |
| Survey. Describe the characteristics of patients who were able to have a child after diagnosis | Evaluation of the characteristics of patients who were able to have a child after diagnosis: o normal puberty | data from patients with a diagnosis between 31/12/1982 and 12/01/2021 and whose opposition to the study is not expressed |
| Survey. Describe the characteristics of patients who were able to have a child after diagnosis | Evaluation of the characteristics of patients who were able to have a child after diagnosis: o age at menarche | data from patients with a diagnosis between 31/12/1982 and 12/01/2021 and whose opposition to the study is not expressed |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
spontaneous pregnancy, adoption, oocyte donation, parental project
|
|
NCT05583123
|
One-piece and Two-piece Zirconia Abutments in Single Implant Crowns in Esthetic Region
|
The goal of this clinical trail is to evaluate the clinical, radiological and immunological outcomes of the one-piece zirconia abutments (OPZAs) and two-piece zirconia abutments (TPZAs) with friction-fitted titanium bases in single implant crowns in aesthetic region. The main question it aims to answer is:~whether the mechanical properties of one-piece zirconia abutments are the same as those of two-piece zirconia abutments.~Participants who have two missing teeth in aesthetic region will receive the OPZAs for one restoration and the TPZAs for the other.~Researchers will compare OPZAs group (OG) and TPZAs group (TG) to see the clinical, radiological and immunological outcomes of the two.
|
Objective: To evaluate the clinical, radiological and immunological outcomes of the one-piece zirconia abutments (OPZAs) and two-piece zirconia abutments (TPZAs) with friction-fitted titanium bases in single implant crowns in aesthetic region.~Materials and methods: The study is a single center, split-mouth and randomized controlled clinical trial. Eligible sites of patients will be randomly assigned into two groups: OPZAs group (OG) and TPZAs group (TG). Survival rates, mechanical complication rates, bleeding on probing (BOP%), probing depth (PD), modified plaque index (mPI), marginal bone loss (MBL), concentrations of pro-inflammatory cytokines (TNF-α, IL-6) in peri-implant crevicular fluid (PICF), and pink esthetics score/white esthetics score (PES/ WES) will be evaluated.~Discussion: Results of the present study will help to evaluate the clinical, radiological and immunological outcomes of OPZAs and TPZAs with friction-fitted titanium bases in single implant crowns in aesthetic region and provide evidence for the effects of two types abutments on the health of peri-implant soft and hard tissue.
|
Evaluation of the One-piece Zirconia Abutments and Two-piece Zirconia Abutments With Titanium Bases for Single Implant Crowns in Esthetic Region: a Randomized Split-mouth Clinical Trial With 1-year Follow-up
|
Partial-edentulism
|
* Device: restored abutment (OPZAs)
* Device: restored abutment (TPZAs)
|
Inclusion Criteria:~age≥18;~patients with two missing teeth in esthetic region and plan to be restored with two single implant crowns;~adjacent to natural teeth;~absence of oral mucosal disease and oral infection;~implants with conical connection (Nobel Active, Nobel Biocare® or NobelReplace Conical Connection, Nobel Biocare®);~patients with the willingness to participate in the present study.~Exclusion Criteria:~heavy smokers (>10 cigarettes/day);~uncontrolled periodontitis (Full mouth plaque score>20%, full mouth bleeding score>25%, residual pocket depth>5mm);~with systematic diseases that may affect implant therapy, such as uncontrolled diabetes mellitus (Fasting blood-glucose>7.2mmol/L, Glycosylated hemoglobin >7%), current intake of bisphosphonates (treatment for malignancy), pregnant(or plan to get pregnant), with history of radiation therapy in head and neck region.
|
18 Years
| null |
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mechanical complications rates | Veneer chipping, abutments or implants fracture, screw loosening or fracture and other mechanical complications will be recorded during the 1-year follow-up. | 1 year |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival rates | The survival rate was defined as the percentage of success implants and remained crowns which never been replaced. | 1 year |
| Peri-implant conditions-BOP% | peri-implant conditions included bleeding on probing% (BOP%) | 1 year |
| Peri-implant conditions-PD | pocket probing depth (PD) in mm | 1 year |
| Peri-implant conditions-mPI | modified plaque index (mPI). | 1 year |
| Marginal bone loss (MBL) | Peri-apical radiographs with paralleling technique will be performed on the day of final restorations delivery and 1 year later. The implant length is used as calibration reference. The distance between restoration margin and the most coronal level of implant-bone contact will be recorded. The final result calculate as the mean value of mesial and distal sites. The alteration of the distance between baseline and 1-year follow-up is defined as the MBL. | 1 year |
| Pro-inflammatory cytokines in peri-implant crevicular fluid (PICF) | We will collect the patients' PICF with the paper strip (PerioPaper Strips; Oraflow Inc., Smithtown, NY, USA) at 1-year follow-up to access differences in pro-inflammatory cytokines (IL-6 and TNF-α) between two groups. Enzyme-linked immunosorbent assay (ELISA) will be used to analyzed PICF and evaluated the concentrations of cytokines. The PICF collection method and cytokines determination referred to Christopher A. Barwacz et al. | 1 year |
| PES | In this study, pink aesthetic score (PES) will be applied for the objective esthetic assessment of the final restoration. We will take patients' intraoral photos by the camera (D70, Nikon, Tokyo, Japan) at 1 year follow up. The aesthetic effect will be assessed by two specific dentists independently. They will asked to give scores for variables of PES (Mesial papilla, distal papilla, level of soft-tissue margin, soft-tissue contour, alveolar process and soft-tissue color and texture) and WES (Tooth form, tooth volume/outline, color, surface texture and transparency) with the 0-1-2 scoring system. Final PES/WES is the sum of the two. | 1 year |
| WES | In this study, white esthetic score (WES) will be applied for the objective esthetic assessment of the final restoration. We will take patients' intraoral photos by the camera (D70, Nikon, Tokyo, Japan) at 1 year follow up. The aesthetic effect will be assessed by two specific dentists independently. They will asked to give scores for variables of PES (Mesial papilla, distal papilla, level of soft-tissue margin, soft-tissue contour, alveolar process and soft-tissue color and texture) and WES (Tooth form, tooth volume/outline, color, surface texture and transparency) with the 0-1-2 scoring system. Final PES/WES is the sum of the two. | 1 year |
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OPZAs group (OG)<br>one-piece zirconia abutments (OPZAs) | Device: restored abutment (OPZAs)<br>* The restorations will be restored by the OPZAs<br>|
| Active Comparator: TPZAs group (TG)<br>two-piece zirconia abutments (TPZAs) with friction-fitted titanium bases | Device: restored abutment (TPZAs)<br>* The restorations will be restored with the TPZAs with friction-fitted titanium bases.<br>|
|
One-piece and Two-piece Zirconia Abutments in Single Implant Crowns in Esthetic Region
Study Overview
=================
Brief Summary
-----------------
The goal of this clinical trail is to evaluate the clinical, radiological and immunological outcomes of the one-piece zirconia abutments (OPZAs) and two-piece zirconia abutments (TPZAs) with friction-fitted titanium bases in single implant crowns in aesthetic region. The main question it aims to answer is: whether the mechanical properties of one-piece zirconia abutments are the same as those of two-piece zirconia abutments. Participants who have two missing teeth in aesthetic region will receive the OPZAs for one restoration and the TPZAs for the other. Researchers will compare OPZAs group (OG) and TPZAs group (TG) to see the clinical, radiological and immunological outcomes of the two.
Detailed Description
-----------------
Objective: To evaluate the clinical, radiological and immunological outcomes of the one-piece zirconia abutments (OPZAs) and two-piece zirconia abutments (TPZAs) with friction-fitted titanium bases in single implant crowns in aesthetic region. Materials and methods: The study is a single center, split-mouth and randomized controlled clinical trial. Eligible sites of patients will be randomly assigned into two groups: OPZAs group (OG) and TPZAs group (TG). Survival rates, mechanical complication rates, bleeding on probing (BOP%), probing depth (PD), modified plaque index (mPI), marginal bone loss (MBL), concentrations of pro-inflammatory cytokines (TNF-α, IL-6) in peri-implant crevicular fluid (PICF), and pink esthetics score/white esthetics score (PES/ WES) will be evaluated. Discussion: Results of the present study will help to evaluate the clinical, radiological and immunological outcomes of OPZAs and TPZAs with friction-fitted titanium bases in single implant crowns in aesthetic region and provide evidence for the effects of two types abutments on the health of peri-implant soft and hard tissue.
Official Title
-----------------
Evaluation of the One-piece Zirconia Abutments and Two-piece Zirconia Abutments With Titanium Bases for Single Implant Crowns in Esthetic Region: a Randomized Split-mouth Clinical Trial With 1-year Follow-up
Conditions
-----------------
Partial-edentulism
Intervention / Treatment
-----------------
* Device: restored abutment (OPZAs)
* Device: restored abutment (TPZAs)
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: age≥18; patients with two missing teeth in esthetic region and plan to be restored with two single implant crowns; adjacent to natural teeth; absence of oral mucosal disease and oral infection; implants with conical connection (Nobel Active, Nobel Biocare® or NobelReplace Conical Connection, Nobel Biocare®); patients with the willingness to participate in the present study. Exclusion Criteria: heavy smokers (>10 cigarettes/day); uncontrolled periodontitis (Full mouth plaque score>20%, full mouth bleeding score>25%, residual pocket depth>5mm); with systematic diseases that may affect implant therapy, such as uncontrolled diabetes mellitus (Fasting blood-glucose>7.2mmol/L, Glycosylated hemoglobin >7%), current intake of bisphosphonates (treatment for malignancy), pregnant(or plan to get pregnant), with history of radiation therapy in head and neck region.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OPZAs group (OG)<br>one-piece zirconia abutments (OPZAs) | Device: restored abutment (OPZAs)<br>* The restorations will be restored by the OPZAs<br>|
| Active Comparator: TPZAs group (TG)<br>two-piece zirconia abutments (TPZAs) with friction-fitted titanium bases | Device: restored abutment (TPZAs)<br>* The restorations will be restored with the TPZAs with friction-fitted titanium bases.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mechanical complications rates | Veneer chipping, abutments or implants fracture, screw loosening or fracture and other mechanical complications will be recorded during the 1-year follow-up. | 1 year |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival rates | The survival rate was defined as the percentage of success implants and remained crowns which never been replaced. | 1 year |
| Peri-implant conditions-BOP% | peri-implant conditions included bleeding on probing% (BOP%) | 1 year |
| Peri-implant conditions-PD | pocket probing depth (PD) in mm | 1 year |
| Peri-implant conditions-mPI | modified plaque index (mPI). | 1 year |
| Marginal bone loss (MBL) | Peri-apical radiographs with paralleling technique will be performed on the day of final restorations delivery and 1 year later. The implant length is used as calibration reference. The distance between restoration margin and the most coronal level of implant-bone contact will be recorded. The final result calculate as the mean value of mesial and distal sites. The alteration of the distance between baseline and 1-year follow-up is defined as the MBL. | 1 year |
| Pro-inflammatory cytokines in peri-implant crevicular fluid (PICF) | We will collect the patients' PICF with the paper strip (PerioPaper Strips; Oraflow Inc., Smithtown, NY, USA) at 1-year follow-up to access differences in pro-inflammatory cytokines (IL-6 and TNF-α) between two groups. Enzyme-linked immunosorbent assay (ELISA) will be used to analyzed PICF and evaluated the concentrations of cytokines. The PICF collection method and cytokines determination referred to Christopher A. Barwacz et al. | 1 year |
| PES | In this study, pink aesthetic score (PES) will be applied for the objective esthetic assessment of the final restoration. We will take patients' intraoral photos by the camera (D70, Nikon, Tokyo, Japan) at 1 year follow up. The aesthetic effect will be assessed by two specific dentists independently. They will asked to give scores for variables of PES (Mesial papilla, distal papilla, level of soft-tissue margin, soft-tissue contour, alveolar process and soft-tissue color and texture) and WES (Tooth form, tooth volume/outline, color, surface texture and transparency) with the 0-1-2 scoring system. Final PES/WES is the sum of the two. | 1 year |
| WES | In this study, white esthetic score (WES) will be applied for the objective esthetic assessment of the final restoration. We will take patients' intraoral photos by the camera (D70, Nikon, Tokyo, Japan) at 1 year follow up. The aesthetic effect will be assessed by two specific dentists independently. They will asked to give scores for variables of PES (Mesial papilla, distal papilla, level of soft-tissue margin, soft-tissue contour, alveolar process and soft-tissue color and texture) and WES (Tooth form, tooth volume/outline, color, surface texture and transparency) with the 0-1-2 scoring system. Final PES/WES is the sum of the two. | 1 year |
|
||
NCT01294228
|
Rapid Evaluation of Acute Kidney Injury With NGAL in Acutely Ill Patients in the ICU
|
This is a multi-center, prospective, observational study of patients that are admitted to the intensive care unit (ICU). This study does not include any treatment or intervention and it is considered Nonsignificant Risk.
|
The study will be conducted in two phases. Phase One is specimen acquisition and subject diagnosis adjudication. Phase Two is biomarker testing.~Phase One~Approximately 850 adults admitted to general ICUs will be enrolled within 12 hours of receipt of ICU admission orders. Study specific whole blood and urine specimens will be collected.~There is an Adjudication Committee for this study. This committee is comprised of qualified, board-certified nephrologists.~Phase Two~During Phase Two, the plasma specimens will be divided amongst three clinical sites representative of the intended end users of this assay, and tested under a separate testing protocol.
|
Rapid Evaluation of Acute Kidney Injury With NGAL in Acutely Ill Patients in the ICU
|
Acute Kidney Injury
|
Inclusion Criteria:~Subjects must be 21 years of age or older.~Subjects must be admitted to an Intensive Care Unit (medical or surgical) and must be enrolled into this study within 12 hours of receipt of ICU admission orders.~Subjects must be assessed as likely to be alive in the ICU for a minimum of 48 hours after enrollment.~The following plasma/serum creatinine values must be available:~Subjects that are admitted to the ICU following an elective surgery or procedure must have at least one pre-surgical/ pre-procedure creatinine value obtained in the 7 days prior to presentation to the ICU.~Subjects that are admitted to the ICU for any reason other than following an elective surgery or procedure must have at least one creatinine value obtained greater than 7 days and up to 6 months prior to presentation to the ICU.~Exclusion Criteria~Subjects either receiving or in imminent need of Renal Replacement Therapy.~Subjects with evidence of chronic kidney disease stages 4 and 5 as evidenced by a pre-enrollment estimated GFR of less than 30 mL/min/1.73M2 (according to the 4-variable MDRD22).~Subjects with any obstructive uropathy at the time of presentation to the ICU.~Subjects with any known urothelial, urological or kidney malignancies.~Subjects that have had any urologic procedure or surgery immediately prior to admission to the ICU.~Subjects that have had any renal transplant or nephrectomy.~Subjects that have had cardiovascular surgery involving cardiopulmonary bypass within the previous 7 days.~Subjects that have participated in an interventional clinical study within the previous 30 days including studies with any investigational and non-investigational drugs.~The inability to obtain written Informed Consent from the subject or an authorized representative.~Subjects that have been previously enrolled in this study during a prior admission to the ICU.
|
21 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Efficacy of the Triage Neutraphil-Gelatinase Associated Lipocalin (NGAL) Test as an Aid in the Diagnosis of Acute Kidney Injury (AKI) in an All-comers ICU Setting. | The efficacy of the Triage Neutraphil-Gelatinase Associated Lipocalin (NGAL) Test as an aid in the diagnosis of acute kidney injury (AKI) in an all-comers ICU setting. Final AKI diagnoses were established by an adjudication committee. | Prior to or within 72 hours. |
|
Acute Kidney Injury, Wounds and Injuries, Renal Insufficiency, Kidney Diseases, Urologic Diseases, Female Urogenital Diseases, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases, Male Urogenital Diseases
|
Rapid Evaluation of Acute Kidney Injury With NGAL in Acutely Ill Patients in the ICU
Study Overview
=================
Brief Summary
-----------------
This is a multi-center, prospective, observational study of patients that are admitted to the intensive care unit (ICU). This study does not include any treatment or intervention and it is considered Nonsignificant Risk.
Detailed Description
-----------------
The study will be conducted in two phases. Phase One is specimen acquisition and subject diagnosis adjudication. Phase Two is biomarker testing. Phase One Approximately 850 adults admitted to general ICUs will be enrolled within 12 hours of receipt of ICU admission orders. Study specific whole blood and urine specimens will be collected. There is an Adjudication Committee for this study. This committee is comprised of qualified, board-certified nephrologists. Phase Two During Phase Two, the plasma specimens will be divided amongst three clinical sites representative of the intended end users of this assay, and tested under a separate testing protocol.
Official Title
-----------------
Rapid Evaluation of Acute Kidney Injury With NGAL in Acutely Ill Patients in the ICU
Conditions
-----------------
Acute Kidney Injury
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects must be 21 years of age or older. Subjects must be admitted to an Intensive Care Unit (medical or surgical) and must be enrolled into this study within 12 hours of receipt of ICU admission orders. Subjects must be assessed as likely to be alive in the ICU for a minimum of 48 hours after enrollment. The following plasma/serum creatinine values must be available: Subjects that are admitted to the ICU following an elective surgery or procedure must have at least one pre-surgical/ pre-procedure creatinine value obtained in the 7 days prior to presentation to the ICU. Subjects that are admitted to the ICU for any reason other than following an elective surgery or procedure must have at least one creatinine value obtained greater than 7 days and up to 6 months prior to presentation to the ICU. Exclusion Criteria Subjects either receiving or in imminent need of Renal Replacement Therapy. Subjects with evidence of chronic kidney disease stages 4 and 5 as evidenced by a pre-enrollment estimated GFR of less than 30 mL/min/1.73M2 (according to the 4-variable MDRD22). Subjects with any obstructive uropathy at the time of presentation to the ICU. Subjects with any known urothelial, urological or kidney malignancies. Subjects that have had any urologic procedure or surgery immediately prior to admission to the ICU. Subjects that have had any renal transplant or nephrectomy. Subjects that have had cardiovascular surgery involving cardiopulmonary bypass within the previous 7 days. Subjects that have participated in an interventional clinical study within the previous 30 days including studies with any investigational and non-investigational drugs. The inability to obtain written Informed Consent from the subject or an authorized representative. Subjects that have been previously enrolled in this study during a prior admission to the ICU.
Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Efficacy of the Triage Neutraphil-Gelatinase Associated Lipocalin (NGAL) Test as an Aid in the Diagnosis of Acute Kidney Injury (AKI) in an All-comers ICU Setting. | The efficacy of the Triage Neutraphil-Gelatinase Associated Lipocalin (NGAL) Test as an aid in the diagnosis of acute kidney injury (AKI) in an all-comers ICU setting. Final AKI diagnoses were established by an adjudication committee. | Prior to or within 72 hours. |
|
|||||
NCT01277770
|
Studies of Kidney Transplant Outcome
|
The purpose of this study is to improve outcome for kidney transplant recipients. There has not been commensurate improvement in medium and long-term outcomes. Ongoing clinical research is necessary to improve transplant outcomes.
|
This study is looking at information already collected of transplant outcomes (short, medium and long-term complications and quality of life). This will specifically look at:~10 year follow-up of steroid-free maintenance immunosuppression~A cross-sectional study of infection after kidney transplantation (with emphasis on infection in steroid-free recipients~An evaluation of the Delayed Graft Function (DGF) nomogram in Thymoglobulin treated recipients at the University of Minnesota
|
Studies of Kidney Transplant Outcome
|
Transplant Recipient (Kidney), Steroid-Free Maintenance Immunosuppression, Post-Transplant Infections, Thymoglobulin
|
* Drug: Steroid-Free Maintenance Immunosuppression
* Other: Infection After Kidney Transplantation
* Drug: Evaluation of the DGF nomogram in Thymoglobulin
|
Inclusion Criteria:~Kidney Transplant Recipient at the University of Minnesota~Kidney Transplant Recipients on steroid-free maintenance immunosuppression~Exclusion Criteria:~Non-kidney transplant patients at the University of Minnesota
| null | null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Data Analysis | All studies are analyses from the Transplant Outcomes Database. Recipients have signed consent to have medical information entered into the database for these analyses. The database contains information on short, medium and long-term results. | 10 year followup |
|
Thymoglobulin, Kidney Transplant Recipients, Steroid-Free, Immunosuppression
|
Thymoglobulin, Antilymphocyte Serum, Immunologic Factors, Physiological Effects of Drugs, Immunosuppressive Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Kidney Transplant Recipients<br>Kidney Transplant Recipients at the University of Minnesota since 1984. The study looks at a 10 year followup of steroid-free maintenance immunosuppression, post-transplant infections and evaluation of the DGF nomogram in Thymoglobulin on patients at the University of Minnesota. | Drug: Steroid-Free Maintenance Immunosuppression<br>* 10 year follow-up of steroid-free maintenance immunosuppression<br>* Other names: Immunosuppression;Other: Infection After Kidney Transplantation<br>* A cross-sectional study of infection after kidney transplantation (with emphasis on infection in steroid-free recipients).<br>* Other names: Steroid-Free;Drug: Evaluation of the DGF nomogram in Thymoglobulin<br>* An evaluation of the DGF nomogram in Thymoglobulin treated recipients at the University of Minnesota<br>* Other names: Thymoglobulin;|
|
Studies of Kidney Transplant Outcome
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to improve outcome for kidney transplant recipients. There has not been commensurate improvement in medium and long-term outcomes. Ongoing clinical research is necessary to improve transplant outcomes.
Detailed Description
-----------------
This study is looking at information already collected of transplant outcomes (short, medium and long-term complications and quality of life). This will specifically look at: 10 year follow-up of steroid-free maintenance immunosuppression A cross-sectional study of infection after kidney transplantation (with emphasis on infection in steroid-free recipients An evaluation of the Delayed Graft Function (DGF) nomogram in Thymoglobulin treated recipients at the University of Minnesota
Official Title
-----------------
Studies of Kidney Transplant Outcome
Conditions
-----------------
Transplant Recipient (Kidney), Steroid-Free Maintenance Immunosuppression, Post-Transplant Infections, Thymoglobulin
Intervention / Treatment
-----------------
* Drug: Steroid-Free Maintenance Immunosuppression
* Other: Infection After Kidney Transplantation
* Drug: Evaluation of the DGF nomogram in Thymoglobulin
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Kidney Transplant Recipient at the University of Minnesota Kidney Transplant Recipients on steroid-free maintenance immunosuppression Exclusion Criteria: Non-kidney transplant patients at the University of Minnesota
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Kidney Transplant Recipients<br>Kidney Transplant Recipients at the University of Minnesota since 1984. The study looks at a 10 year followup of steroid-free maintenance immunosuppression, post-transplant infections and evaluation of the DGF nomogram in Thymoglobulin on patients at the University of Minnesota. | Drug: Steroid-Free Maintenance Immunosuppression<br>* 10 year follow-up of steroid-free maintenance immunosuppression<br>* Other names: Immunosuppression;Other: Infection After Kidney Transplantation<br>* A cross-sectional study of infection after kidney transplantation (with emphasis on infection in steroid-free recipients).<br>* Other names: Steroid-Free;Drug: Evaluation of the DGF nomogram in Thymoglobulin<br>* An evaluation of the DGF nomogram in Thymoglobulin treated recipients at the University of Minnesota<br>* Other names: Thymoglobulin;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Data Analysis | All studies are analyses from the Transplant Outcomes Database. Recipients have signed consent to have medical information entered into the database for these analyses. The database contains information on short, medium and long-term results. | 10 year followup |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Thymoglobulin, Kidney Transplant Recipients, Steroid-Free, Immunosuppression
|
||
NCT01291667
|
Study for HER2-Overexpressed MBC Patients Treated by Cipterbin® Plus vinorelbinE
|
Breast cancer is the most common malignant disease and the most frequent causes of cancer mortality in females worldwide. The situation is same as the world in China. Trastuzumab has been proved valuable treatment for HER2-positive breast cancer patients. Cipterbin® is developing by Shanghai CP Guojian Pharmaceutical Co.Ltd.Now we carried on the phase III trial in order to prove Cipterbin® 's efficacy and safety.
|
A Phase III Randomized Study for HER2-Overexpressed Metastatic Breast Cancer Patients Treated by Trastuzumab( Cipterbin®) Plus vinorelbinE Simultaneously or Sequencely
|
Progress-free Survival, Overall Response Rate, Adverse Events
|
Inclusion Criteria:~signed ICF~pathologic diagnosis breast cancer~HER2+ status defined as IHC3+ Staining or in situ hybridization positive at least 1 measurable lesion as per RECIST criteria age from 18y to 70y KPS>=70~Exclusion Criteria:~More than three prior chemotherapy lines for advanced disease LVEF<50%~prior exposure vinorebine for breast cancer~prior exposure Trastuzumab for breast cancer~uncontrolled brain metastasis~breastfeeding or pregnant
|
18 Years
|
70 Years
|
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progress-free survival | | |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall response rate,safety | | |
|
Study for HER2-Overexpressed MBC Patients Treated by Cipterbin® Plus vinorelbinE
Study Overview
=================
Brief Summary
-----------------
Breast cancer is the most common malignant disease and the most frequent causes of cancer mortality in females worldwide. The situation is same as the world in China. Trastuzumab has been proved valuable treatment for HER2-positive breast cancer patients. Cipterbin® is developing by Shanghai CP Guojian Pharmaceutical Co.Ltd.Now we carried on the phase III trial in order to prove Cipterbin® 's efficacy and safety.
Official Title
-----------------
A Phase III Randomized Study for HER2-Overexpressed Metastatic Breast Cancer Patients Treated by Trastuzumab( Cipterbin®) Plus vinorelbinE Simultaneously or Sequencely
Conditions
-----------------
Progress-free Survival, Overall Response Rate, Adverse Events
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: signed ICF pathologic diagnosis breast cancer HER2+ status defined as IHC3+ Staining or in situ hybridization positive at least 1 measurable lesion as per RECIST criteria age from 18y to 70y KPS>=70 Exclusion Criteria: More than three prior chemotherapy lines for advanced disease LVEF<50% prior exposure vinorebine for breast cancer prior exposure Trastuzumab for breast cancer uncontrolled brain metastasis breastfeeding or pregnant
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progress-free survival | | |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall response rate,safety | | |
|
||||||
NCT01278485
|
Evaluation of Low Blood Sugar Events in Participants With Diabetes (MK-0431-402)
|
This is a multicenter, observational, retrospective and cross-sectional study to be conducted in a cohort of consecutively selected participants with type 2 diabetes mellitus (T2DM) who have been treated with sulphonylurea (SU) monotherapy or SU + metformin (MF) combination therapy by their cardiologist, nephrologist, or family practice doctor for at least 6 months prior to study enrollment.~The purpose of the study is to assess treatment patterns, goal attainment rates, long-term diabetes complication rates, and frequency and severity of hypoglycemic episodes among T2DM participants treated in cardiology, nephrology and family practice settings.
|
Naturalistic Evaluation of Hypoglycemic Events in Diabetic Subjects
|
Type 2 Diabetes Mellitus
|
* Drug: Sulphonylurea
* Drug: Metformn
|
Inclusion Criteria~Participants diagnosed with type 2 diabetes mellitus (DM).~Participants at least 30 years of age at time of type 2 DM diagnosis.~Participants treated with SU monotherapy or SU + MF combination therapy for at least 6 months prior to enrollment.~Participants receiving diabetes care from a cardiologist, nephrologist or family practitioner for at least 6 months.~Participants with a clinical record in the health care center.~Participants in whose medical records a minimum core data set can be found; core data defined as: age, gender, duration of diabetes/age at diagnosis, all glucose-lowering medications (branded and generic names, dosage, dosing frequency, starting and stopping dates) since the start of all antihyperglycemic medications.~Exclusion Criteria~Participants with Type 1 DM.~Participants who are pregnant or with gestational DM.~Participants receiving any anti-diabetic treatment from an endocrinologist/diabetologist in the previous 6 months.~Participants requiring daily concomitant usage of insulin.~Participants receiving any other oral diabetes medications other than SU or SU + MF.~Participants who are already participating in a clinical trial or other clinical study.~Participants for whom it would be impossible to complete the questionnaire.
|
30 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing Hypoglycemic Episodes in the 6 Months Prior to Enrollment | The participant experience of low blood sugar (hypoglycemia) questionnaire was used to evaluate participants' experience of hypoglycemia during the previous 6 months. Participants were asked to record whether they experienced hypoglycemia symptoms (yes/no) and to record the severity of those symptoms as mild, moderate, severe, or very severe. | Up to 6 Months Prior to Enrollment |
| Number of Participants Experiencing Mild, Moderate, Severe, or Very Severe Hypoglycemic Episodes in the 6 Months Prior to Enrollment | At the time of enrollment, participants were asked to rate their hypoglycemic episodes in the last 6 months as mild, moderate, severe, or very severe. Participants were able to select more than one category. | Up to 6 Months Prior to Enrollment |
| Number of Participants With Hemoglobin A1c <7.0% at the Time of Enrollment | Participant serum samples were collected after an overnight fast to determine the hemoglobin A1c level. Hemoglobin A1c is a measure of the percentage of glycated hemoglobin in the blood and provides an indication of participant blood glucose control in the 2 to 3 months prior to the evaluation. | Day of Enrollment |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participant Mean Score on the EuroQol-5 Dimension (EQ-5D) Quality-of-Life Questionnaire At the Time of Enrollment | The EQ-5D is a questionnaire that assesses participant quality of life in 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each domain has 3 levels: no problems, some problems, extreme problems for which participants are asked to self-rate their experience. The EQ-5D total score ranges from -0.171 (worst health state) to 1 (perfect health state) and 1 reflects the best outcome. | Day of Enrollment |
| Participant Mean Score on the EuroQol Visual Analog Scale (EQ-VAS) Quality-of-Life Questionnaire At the Time of Enrollment | Participant health status was self-reported in 5 domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and was analyzed by using visual analog scale (VAS) which records participant responses on a scale of 0 (poor health) to 100 (excellent health). | Day of Enrollment |
| Participant Mean Score on the Treatment Satisfaction Questionnaire for Medication (TSQM) At the Time of Enrollment | The TSQM is a treatment satisfaction questionnaire containing 14 items covering the following dimensions: side effects, effectiveness, convenience, and global satisfaction. Participants were asked to respond in a yes or no fashion, or by using a 5- or 7-point Likert scale. The score for each dimension ranges from 0 to 100, with a higher score expressing a better quality of life. | Day of Enrollment |
| Participant Mean Score on the Self-Reported Adherence and Barriers Questionnaire At the Time of Enrollment | The self-reported adherence and barriers questionnaire to measure treatment compliance asked participants to rate their responses to 5 questions: How often do you take your diabetes medicines exactly as your healthcare provider prescribes them?; During the past 4 weeks, how often were you unsure about some of the things your doctor suggested you do for your diabetes?; During the past 4 weeks, how often were you unable to do what was necessary to follow your doctor's treatment plans for your diabetes?; During the past 4 weeks, how often were you bothered by side effects from your medicines?; and During the past 4 weeks, how often did you have problems getting your prescriptions filled? Participants responded using a scale of 1 to 5, where 1=always, 2=usually, 3=sometimes, 4=rarely, and 5=never. | Day of Enrollment |
| Participant Mean Score on the Worry Scale of Hypoglycemia Fear Survey (HFS II) At the Time of Enrollment | Fear about hypoglycemia during 6 months prior to enrollment was evaluated using the Worry Scale of the HFS II. Responses to the 18-item questionnaire were recorded on a 0 to 4 scale, with 0=never, 1=rarely, 2=sometimes, 3=often, 4=almost always. The total score ranges from 0 to 72, with higher scores indicating increasing fear of hypoglycemia. | Day of Enrollment |
| Number of Participants Experiencing a Change in Body Weight in the 12 Months Prior to Enrollment | Participants were asked to rate their weight change experience in the 12 months prior to enrollment as: weight increased, weight decreased, or weight remained stable. | Up to 12 Months Prior to Enrollment |
| Number of Participants Reporting Body Weight Fears in the 12 Months Prior to Enrollment | On the day of enrollment, participants were asked to rate their fear of gaining weight in the 12 months prior to enrollment using a self-administered questionnaire. The questionnaire elicited responses to 3 statements (I worry about gaining weight; I worry that my diabetic treatment makes me gain weight; and I worry about not being able to stabilize my weight) and relied on a scale of 0 to 4, where 0=never, 1=rarely, 2=sometimes, 3=often, and 4=almost always. | Up to 12 Months Prior to Enrollment |
|
Diabetes complications
|
Diabetes Mellitus, Type 2, Diabetes Mellitus, Glucose Metabolism Disorders, Metabolic Diseases, Endocrine System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sulphonylurea (SU) Monotherapy or SU + Metformin<br>Participants with Type 2 diabetes that have been treated with SU monotherapy for at least 6 months by a cardiologist, nephrologist, or family practice doctor. | Drug: Sulphonylurea<br>* SU administered according to usual practice.<br>Drug: Metformn<br>* Metformin administered according to usual practice.<br>|
|
Evaluation of Low Blood Sugar Events in Participants With Diabetes (MK-0431-402)
Study Overview
=================
Brief Summary
-----------------
This is a multicenter, observational, retrospective and cross-sectional study to be conducted in a cohort of consecutively selected participants with type 2 diabetes mellitus (T2DM) who have been treated with sulphonylurea (SU) monotherapy or SU + metformin (MF) combination therapy by their cardiologist, nephrologist, or family practice doctor for at least 6 months prior to study enrollment. The purpose of the study is to assess treatment patterns, goal attainment rates, long-term diabetes complication rates, and frequency and severity of hypoglycemic episodes among T2DM participants treated in cardiology, nephrology and family practice settings.
Official Title
-----------------
Naturalistic Evaluation of Hypoglycemic Events in Diabetic Subjects
Conditions
-----------------
Type 2 Diabetes Mellitus
Intervention / Treatment
-----------------
* Drug: Sulphonylurea
* Drug: Metformn
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Participants diagnosed with type 2 diabetes mellitus (DM). Participants at least 30 years of age at time of type 2 DM diagnosis. Participants treated with SU monotherapy or SU + MF combination therapy for at least 6 months prior to enrollment. Participants receiving diabetes care from a cardiologist, nephrologist or family practitioner for at least 6 months. Participants with a clinical record in the health care center. Participants in whose medical records a minimum core data set can be found; core data defined as: age, gender, duration of diabetes/age at diagnosis, all glucose-lowering medications (branded and generic names, dosage, dosing frequency, starting and stopping dates) since the start of all antihyperglycemic medications. Exclusion Criteria Participants with Type 1 DM. Participants who are pregnant or with gestational DM. Participants receiving any anti-diabetic treatment from an endocrinologist/diabetologist in the previous 6 months. Participants requiring daily concomitant usage of insulin. Participants receiving any other oral diabetes medications other than SU or SU + MF. Participants who are already participating in a clinical trial or other clinical study. Participants for whom it would be impossible to complete the questionnaire.
Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sulphonylurea (SU) Monotherapy or SU + Metformin<br>Participants with Type 2 diabetes that have been treated with SU monotherapy for at least 6 months by a cardiologist, nephrologist, or family practice doctor. | Drug: Sulphonylurea<br>* SU administered according to usual practice.<br>Drug: Metformn<br>* Metformin administered according to usual practice.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing Hypoglycemic Episodes in the 6 Months Prior to Enrollment | The participant experience of low blood sugar (hypoglycemia) questionnaire was used to evaluate participants' experience of hypoglycemia during the previous 6 months. Participants were asked to record whether they experienced hypoglycemia symptoms (yes/no) and to record the severity of those symptoms as mild, moderate, severe, or very severe. | Up to 6 Months Prior to Enrollment |
| Number of Participants Experiencing Mild, Moderate, Severe, or Very Severe Hypoglycemic Episodes in the 6 Months Prior to Enrollment | At the time of enrollment, participants were asked to rate their hypoglycemic episodes in the last 6 months as mild, moderate, severe, or very severe. Participants were able to select more than one category. | Up to 6 Months Prior to Enrollment |
| Number of Participants With Hemoglobin A1c <7.0% at the Time of Enrollment | Participant serum samples were collected after an overnight fast to determine the hemoglobin A1c level. Hemoglobin A1c is a measure of the percentage of glycated hemoglobin in the blood and provides an indication of participant blood glucose control in the 2 to 3 months prior to the evaluation. | Day of Enrollment |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participant Mean Score on the EuroQol-5 Dimension (EQ-5D) Quality-of-Life Questionnaire At the Time of Enrollment | The EQ-5D is a questionnaire that assesses participant quality of life in 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each domain has 3 levels: no problems, some problems, extreme problems for which participants are asked to self-rate their experience. The EQ-5D total score ranges from -0.171 (worst health state) to 1 (perfect health state) and 1 reflects the best outcome. | Day of Enrollment |
| Participant Mean Score on the EuroQol Visual Analog Scale (EQ-VAS) Quality-of-Life Questionnaire At the Time of Enrollment | Participant health status was self-reported in 5 domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and was analyzed by using visual analog scale (VAS) which records participant responses on a scale of 0 (poor health) to 100 (excellent health). | Day of Enrollment |
| Participant Mean Score on the Treatment Satisfaction Questionnaire for Medication (TSQM) At the Time of Enrollment | The TSQM is a treatment satisfaction questionnaire containing 14 items covering the following dimensions: side effects, effectiveness, convenience, and global satisfaction. Participants were asked to respond in a yes or no fashion, or by using a 5- or 7-point Likert scale. The score for each dimension ranges from 0 to 100, with a higher score expressing a better quality of life. | Day of Enrollment |
| Participant Mean Score on the Self-Reported Adherence and Barriers Questionnaire At the Time of Enrollment | The self-reported adherence and barriers questionnaire to measure treatment compliance asked participants to rate their responses to 5 questions: How often do you take your diabetes medicines exactly as your healthcare provider prescribes them?; During the past 4 weeks, how often were you unsure about some of the things your doctor suggested you do for your diabetes?; During the past 4 weeks, how often were you unable to do what was necessary to follow your doctor's treatment plans for your diabetes?; During the past 4 weeks, how often were you bothered by side effects from your medicines?; and During the past 4 weeks, how often did you have problems getting your prescriptions filled? Participants responded using a scale of 1 to 5, where 1=always, 2=usually, 3=sometimes, 4=rarely, and 5=never. | Day of Enrollment |
| Participant Mean Score on the Worry Scale of Hypoglycemia Fear Survey (HFS II) At the Time of Enrollment | Fear about hypoglycemia during 6 months prior to enrollment was evaluated using the Worry Scale of the HFS II. Responses to the 18-item questionnaire were recorded on a 0 to 4 scale, with 0=never, 1=rarely, 2=sometimes, 3=often, 4=almost always. The total score ranges from 0 to 72, with higher scores indicating increasing fear of hypoglycemia. | Day of Enrollment |
| Number of Participants Experiencing a Change in Body Weight in the 12 Months Prior to Enrollment | Participants were asked to rate their weight change experience in the 12 months prior to enrollment as: weight increased, weight decreased, or weight remained stable. | Up to 12 Months Prior to Enrollment |
| Number of Participants Reporting Body Weight Fears in the 12 Months Prior to Enrollment | On the day of enrollment, participants were asked to rate their fear of gaining weight in the 12 months prior to enrollment using a self-administered questionnaire. The questionnaire elicited responses to 3 statements (I worry about gaining weight; I worry that my diabetic treatment makes me gain weight; and I worry about not being able to stabilize my weight) and relied on a scale of 0 to 4, where 0=never, 1=rarely, 2=sometimes, 3=often, and 4=almost always. | Up to 12 Months Prior to Enrollment |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Diabetes complications
|
||
NCT03060148
|
Spinal Cord Stimulation in Heart Failure
|
Previous studies have shown that spinal cord stimulation (SCS) may improve cardiac output and decrease the risk of ischemic ventricular arrhythmia in animal model and its safety profile in human trial. The purposes of this study are to evaluate the feasibility, treatment efficacy and safety of SCS in patients with severe symptomatic heart failure (HF).
|
Morbidity and mortality in heart failure (HF) patients remain high, even with recent advances in therapies. Previous studies have shown that the autonomic nervous system plays an important role in the pathophysiology of HF and sudden cardiac death.~Spinal cord stimulation (SCS) is a neurostimulation therapy, which involves the stimulation of selected nerve fibers and intends to create end-organ responses characterized by changes in blood flow, decrease of catecholamines and reduction in inflammation. The SCS system consists of an implantable pulse generator (IPG) and dual leads. Each lead has electrodes on the distal end. Electrical impulses travel from the IPG through the leads to the electrodes positioned at the selected nerve fibers to provide the therapeutic stimulation. By virtue of its potential in augmenting blood flow, decreasing catecholamines and reducing inflammation, SCS may benefit HF patients.
|
The Treatment of Spinal Cord Stimulation in Severe Heart Failure
|
Heart Failure
|
* Device: Medtronic neurostimulation system
|
Inclusion Criteria:~Patients has a left ventricular ejection fraction between 20% and 35%~Patient is in New York Heart Association Class III or in Ambulatory Class IV~Patient is receiving stable medical therapy for HF (>90 days) at baseline~Patient has a left ventricular end diastolic diameter between 55 mm and 80 mm~Patient must be able and willing to provide written informed consent to participate in this study~Patient must be able and willing to comply with the required follow-up schedule~Exclusion Criteria:~Patient currently has an implanted spinal cord stimulator or previously had an implanted upper thoracic spinal cord stimulator which is now explanted~Patient has polyneuropathy~Patient requires short-wave diathermy, microwave diathermy or therapeutic ultrasound diathermy~Patient has received a tissue/organ transplant (or is expected to have a tissue/organ transplant within the next 180 days)~Patient has persistent or permanent atrial fibrillation~Patient has chronic refractory angina or peripheral vascular pain~Patient has critical valvular heart disease that requires valve repair or replacement~Patient has had a myocardial infarction (MI) or cardiac revascularization procedure (percutaneous coronary intervention or coronary artery bypass graft) <90 days at baseline or is expected to have this in the next 180 days~Patient is on IV inotropic therapy~Patient has active myocarditis or early postpartum cardiomyopathy~Patient has taken any of the following drugs within 30 days of enrollment: systemic corticosteroids, cytostatic and immunosuppressive drug therapy (cyclophosphamide, methotrexate, cyclosporine, azathioprine, etc.), DNA depleting or cytotoxic drugs~Patient is pregnant, or of childbearing potential and is not using adequate contraceptive methods, or nursing~Patient with a bleeding tendency (International Normalized Ratio >1.2 and platelet count <100 x10^9 per liter)~Patient has a local infection at the implantable cardioverter-defibrillator (ICD) implant location or systemic infection~Patient has renal insufficiency (creatinine >3.0 mg/dl)~Patient is participating in another clinical study~Patient is less than 20 years old~Patient's life's expectancy is less than 1 years as assessed by investigator
|
20 Years
|
100 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Medtronic neurostimulation
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of efficacy markers | Efficacy markers include peak oxygen uptake, New York Heart Association functional class, left ventricular structure and function (left ventricular end-systolic volume and ejection fraction), B-type natriuretic peptide, Minnesota Living with Heart Failure Questionnaire score: Improvement: +1; no change:0; worsening: -1. | 6 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post procedural adverse events | Post-procedure adverse events include implanted procedure related events, system related events and system modification related events. | 24 months |
|
Heart failure, Spinal cord stimulation
|
Heart Failure, Heart Diseases, Cardiovascular Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Spinal cord stimulation<br>Medtronic neurostimulation system for spinal cord stimulation | Device: Medtronic neurostimulation system<br>* Dual leads for spinal cord stimulation will be performed at 90% of the motor threshold for 24 hours/day at 50 Hz and pulse width 0.2 ms<br>* Other names: Medtronic Restore Sensor™ Neurostimulation System;|
| No Intervention: Control<br>No implantation of Medtronic neurostimulation system | |
|
Spinal Cord Stimulation in Heart Failure
Study Overview
=================
Brief Summary
-----------------
Previous studies have shown that spinal cord stimulation (SCS) may improve cardiac output and decrease the risk of ischemic ventricular arrhythmia in animal model and its safety profile in human trial. The purposes of this study are to evaluate the feasibility, treatment efficacy and safety of SCS in patients with severe symptomatic heart failure (HF).
Detailed Description
-----------------
Morbidity and mortality in heart failure (HF) patients remain high, even with recent advances in therapies. Previous studies have shown that the autonomic nervous system plays an important role in the pathophysiology of HF and sudden cardiac death. Spinal cord stimulation (SCS) is a neurostimulation therapy, which involves the stimulation of selected nerve fibers and intends to create end-organ responses characterized by changes in blood flow, decrease of catecholamines and reduction in inflammation. The SCS system consists of an implantable pulse generator (IPG) and dual leads. Each lead has electrodes on the distal end. Electrical impulses travel from the IPG through the leads to the electrodes positioned at the selected nerve fibers to provide the therapeutic stimulation. By virtue of its potential in augmenting blood flow, decreasing catecholamines and reducing inflammation, SCS may benefit HF patients.
Official Title
-----------------
The Treatment of Spinal Cord Stimulation in Severe Heart Failure
Conditions
-----------------
Heart Failure
Intervention / Treatment
-----------------
* Device: Medtronic neurostimulation system
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients has a left ventricular ejection fraction between 20% and 35% Patient is in New York Heart Association Class III or in Ambulatory Class IV Patient is receiving stable medical therapy for HF (>90 days) at baseline Patient has a left ventricular end diastolic diameter between 55 mm and 80 mm Patient must be able and willing to provide written informed consent to participate in this study Patient must be able and willing to comply with the required follow-up schedule Exclusion Criteria: Patient currently has an implanted spinal cord stimulator or previously had an implanted upper thoracic spinal cord stimulator which is now explanted Patient has polyneuropathy Patient requires short-wave diathermy, microwave diathermy or therapeutic ultrasound diathermy Patient has received a tissue/organ transplant (or is expected to have a tissue/organ transplant within the next 180 days) Patient has persistent or permanent atrial fibrillation Patient has chronic refractory angina or peripheral vascular pain Patient has critical valvular heart disease that requires valve repair or replacement Patient has had a myocardial infarction (MI) or cardiac revascularization procedure (percutaneous coronary intervention or coronary artery bypass graft) <90 days at baseline or is expected to have this in the next 180 days Patient is on IV inotropic therapy Patient has active myocarditis or early postpartum cardiomyopathy Patient has taken any of the following drugs within 30 days of enrollment: systemic corticosteroids, cytostatic and immunosuppressive drug therapy (cyclophosphamide, methotrexate, cyclosporine, azathioprine, etc.), DNA depleting or cytotoxic drugs Patient is pregnant, or of childbearing potential and is not using adequate contraceptive methods, or nursing Patient with a bleeding tendency (International Normalized Ratio >1.2 and platelet count <100 x10^9 per liter) Patient has a local infection at the implantable cardioverter-defibrillator (ICD) implant location or systemic infection Patient has renal insufficiency (creatinine >3.0 mg/dl) Patient is participating in another clinical study Patient is less than 20 years old Patient's life's expectancy is less than 1 years as assessed by investigator
Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 100 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Medtronic neurostimulation
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Spinal cord stimulation<br>Medtronic neurostimulation system for spinal cord stimulation | Device: Medtronic neurostimulation system<br>* Dual leads for spinal cord stimulation will be performed at 90% of the motor threshold for 24 hours/day at 50 Hz and pulse width 0.2 ms<br>* Other names: Medtronic Restore Sensor™ Neurostimulation System;|
| No Intervention: Control<br>No implantation of Medtronic neurostimulation system | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of efficacy markers | Efficacy markers include peak oxygen uptake, New York Heart Association functional class, left ventricular structure and function (left ventricular end-systolic volume and ejection fraction), B-type natriuretic peptide, Minnesota Living with Heart Failure Questionnaire score: Improvement: +1; no change:0; worsening: -1. | 6 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post procedural adverse events | Post-procedure adverse events include implanted procedure related events, system related events and system modification related events. | 24 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Heart failure, Spinal cord stimulation
|
NCT04700215
|
Comparison of BiPAP and ٰIS in Reducing Post CABG Pulmonary Complications
|
To evaluate the effect of Bi-level Positive Airway Pressure (BiPAP) and Incentive Spirometry (IS) in post CABG patients.
|
As postoperative pulmonary complications are major concern in cardiac surgery patients and our local data is deficient for making better management guidelines. My study aims to provide a base for future research on this dimension and to decide better management plan for post cardiac surgical pulmonary complications. The hypothesis is Post extubation BiPAP is more effective than Incentive Spirometry (IS) in reducing postoperative pulmonary complications in cardiac surgical patients and the purpose of the study is to evaluate the effect of Bi-level Positive Airway Pressure (BiPAP) and Incentive Spirometry (IS) in cardiac surgical patients.~This Randomized Controlled Trial (RCT) study will be conducted at Chaudhary pervaiz elahi institute of cardiology ICU multan.~A sample size of 350 patients will be taken and effect of BiPAP and Incentive spirometry will be studied in reducing pulmonary complications post CABG surgery. Data will be analyzed through SPSS. For quantitative variables, mean and standard deviation will be calculated and for qualitative variables, frequency and percentage will be calculated. Chi square test will be used to estimate association between qualitative variables. A p value < 0.05 will be significant.
|
Comparison of Effectiveness of Bilevel Positive Airway Pressure and Incentive Spirometry in Reducing Post CABG Surgery Pulmonary Complications
|
Pulmonary Complications
|
* Device: BiPAP
* Device: Incentive spirometry
|
Inclusion Criteria:~CABG patients~Patient willing to study~Patients planned for on-pump cardiac surgical procedures~Both genders (Male & Female)~Age 20-60 years~Ejection fraction 40-60%~Exclusion Criteria:~Patients with valvular lesions~Off-pump cardiac surgery~Refusal to give consent for BiPAP~Emergency surgery~Previous cardiac surgery~Obesity BMI>30~ASA status V
|
20 Years
|
60 Years
|
All
|
No
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post CABG pulmonary complications | To see the effect of BiPAP and IS in reducing post CABG pulmonary complications | 06 months |
|
IS, CABG, BiPAP
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 01 Effectiveness of BiPAP in reducing post CABG pulmonary complications<br>Bilevel positive airway pressure device after every 6 hours | Device: BiPAP<br>* To give bilevel positive airway pressure to the lungs<br>* Other names: Bilevel;|
| Active Comparator: Group 02 Effectiveness of IS in reducing post CABG pulmonary complications<br>Incentive spirometry for 15 minutes after every 4 hours | Device: Incentive spirometry<br>* IS for 15 minutes after every 4 hours<br>|
|
Comparison of BiPAP and ٰIS in Reducing Post CABG Pulmonary Complications
Study Overview
=================
Brief Summary
-----------------
To evaluate the effect of Bi-level Positive Airway Pressure (BiPAP) and Incentive Spirometry (IS) in post CABG patients.
Detailed Description
-----------------
As postoperative pulmonary complications are major concern in cardiac surgery patients and our local data is deficient for making better management guidelines. My study aims to provide a base for future research on this dimension and to decide better management plan for post cardiac surgical pulmonary complications. The hypothesis is Post extubation BiPAP is more effective than Incentive Spirometry (IS) in reducing postoperative pulmonary complications in cardiac surgical patients and the purpose of the study is to evaluate the effect of Bi-level Positive Airway Pressure (BiPAP) and Incentive Spirometry (IS) in cardiac surgical patients. This Randomized Controlled Trial (RCT) study will be conducted at Chaudhary pervaiz elahi institute of cardiology ICU multan. A sample size of 350 patients will be taken and effect of BiPAP and Incentive spirometry will be studied in reducing pulmonary complications post CABG surgery. Data will be analyzed through SPSS. For quantitative variables, mean and standard deviation will be calculated and for qualitative variables, frequency and percentage will be calculated. Chi square test will be used to estimate association between qualitative variables. A p value < 0.05 will be significant.
Official Title
-----------------
Comparison of Effectiveness of Bilevel Positive Airway Pressure and Incentive Spirometry in Reducing Post CABG Surgery Pulmonary Complications
Conditions
-----------------
Pulmonary Complications
Intervention / Treatment
-----------------
* Device: BiPAP
* Device: Incentive spirometry
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: CABG patients Patient willing to study Patients planned for on-pump cardiac surgical procedures Both genders (Male & Female) Age 20-60 years Ejection fraction 40-60% Exclusion Criteria: Patients with valvular lesions Off-pump cardiac surgery Refusal to give consent for BiPAP Emergency surgery Previous cardiac surgery Obesity BMI>30 ASA status V
Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 60 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 01 Effectiveness of BiPAP in reducing post CABG pulmonary complications<br>Bilevel positive airway pressure device after every 6 hours | Device: BiPAP<br>* To give bilevel positive airway pressure to the lungs<br>* Other names: Bilevel;|
| Active Comparator: Group 02 Effectiveness of IS in reducing post CABG pulmonary complications<br>Incentive spirometry for 15 minutes after every 4 hours | Device: Incentive spirometry<br>* IS for 15 minutes after every 4 hours<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post CABG pulmonary complications | To see the effect of BiPAP and IS in reducing post CABG pulmonary complications | 06 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
IS, CABG, BiPAP
|
||
NCT02528435
|
Understanding Methotrexate Induced Gastrointestinal Intolerance in Juvenile Idiopathic Arthritis and Childhood Leukemia
|
Methotrexate is a cornerstone in the treatment of childhood leukemia. When given in high-dose as part of the initial phase of treatment, gastrointestinal toxicity is a known problem. However when children reach maintenance treatment with low-dose methotrexate this is not described as a significant challenge. Children with juvenile idiopathic arthritis are another patient group receiving low-dose methotrexate. Among these patients gastrointestinal intolerance is such a significant problem that treatment may be ceased. The aim of this project is to create a greater understanding of gastrointestinal intolerance associated to low-dose methotrexate treatment by investigating the differences between these two patient groups, investigating genetic and psychological factors.
|
Background:~Childhood leukemia (Acute Lymphoblastic Leukemia, ALL) is the most frequent malignancy in the pediatric population (1). Survival rates have reached above 85% due to advances in chemotherapy. High-dose methotrexate (MTX) is a mainstay in the treatment of ALL (2-4). Gastrointestinal toxicity is a well known challenge associated to high-dose MTX treatment (5). However this is not described as a significant problem among these children when they reach maintenance treatment and receive low-dose MTX treatment. Children with Juvenile Idiopathic Arthritis (JIA) also receive low-dose MTX treatment. Among these patients MTX induced gastrointestinal intolerance is a significant problem. Studies have shown that more than half of the JIA patients have problems tolerating MTX because of nausea which may lead to cessation of treatment (6,7). It is largely unknown why MTX causes nausea but both pharmacogenetic and psychological factors are thought to play a role (8).~JIA is the most common chronic pediatric rheumatic disease. Without treatment the disease causes significant short- and long-term disability and quality of life impairment. Prognosis has greatly improved within recent years as a result of substantial progress in disease management and MTX is a mainstay in the treatment of JIA (9-13).~The aim of this project is to create a greater understanding of MTX induced gastrointestinal intolerance among children with leukemia and children with JIA. The project will focus on nausea and investigate the level of nausea in the two patient groups and compare if a difference does exist. The investigators will further investigate pharmacogenetic and psychological factors and their relation to the patients' level of nausea.~Pharmacogenetic background:~MTX is absorbed from the gastrointestinal tract and transported to the bloodstream by transporter proteins in the enterocytes. Elimination of MTX is primarily renal but a percentage of MTX passes through enterohepatic circulation first (14,15). Studies on the use of high-dose MTX treatment to children with ALL suggest that fast hepatic clearance of MTX increases the degree of gastrointestinal toxicity. It has further been shown that patients with mutations (Single Nucleotide Peptides, SNPs) in the gene encoding the hepatic transporter protein SLCO1B1, responsible for transporting MTX into the liver, have less gastrointestinal toxicity to high-dose MTX (16). The transporter protein encoded by SLC19A1 is placed both in the liver and the enterocytes (15).~Studies on adult patients diagnosed with either psoriasis or rheumatoid arthritis and treated with low-dose MTX, and studies on ALL patients in high-dose MTX show that SLC19A1 is associated to the concentration of MTX in plasma and erythrocytes as well as MTX-related toxicity (1,17-20). Transporter proteins that transport MTX out of the liver and into the bile ducts are encoded by ABCC2 and ABCB1(15). Studies on adult patients with rheumatoid arthritis in low-dose MTX, adults with Chronic Myeloid Leukemia and studies on ALL patients in high-dose MTX have shown that both genes are pharmacokinetically important and ABCC2 has further been shown associated to MTX-related gastrointestinal toxicity (5,21-24). Previous studies on patients with rheumatoid arthritis, childhood leukemia and JIA have shown that the frequency of clinically relevant SNPs in genes encoding MTX-related transporter proteins are: SLCO1B1 (70.3%), ABCB1 (20.6%), ABCC2 (56.8%), SLC19A1 (31%) (5,16,17,19,21,25-28).The investigators therefore believe it conceivable to find the selected genetic polymorphisms for MTX-related transporter proteins in the participating study population.~Pharmocogenetic Aims:~Investigate if MTX-related gastrointestinal intolerance is associated to the enterohepatic circulation. Specifically, to determine if SNPs in genes encoding MTX-related liver transporter proteins are associated to the level of drug induced gastrointestinal side effects.~Pharmacogenetic Hypotheses:~Patients with SNPs in genes encoding MTX-related transporter proteins in the liver have a lower level of enterohepatic circulation of MTX and thus have a lower level of nausea than other patients.~Psychological Background:~Studies on adult cancer patients have shown that psychologically based nausea occurring after treatment with chemotherapy is a possible explanation for the nausea which is out of proportion with the medicine's emetogenic potential. It is also a possible explanation for the great variation in the level of cancer patients' nausea after the same type of chemotherapy (29,30). Studies on children in chemotherapy for different cancers have shown that psychological factors, such as coping strategies and anxiety, affect the degree of chemotherapy associated nausea and vomiting (31-33). The investigators want to investigate if this is also the case for children with leukemia in maintenance treatment with low-dose MTX as well as JIA patients in low-dose MTX-treatment.~Psychological aims:~To investigate if the nausea-coping strategies and anxiety level of the study population are associated to the degree of MTX-induced gastrointestinal intolerance. And investigate if there is a difference between the two patient groups.~Psychological hypotheses:~Insufficient psychological coping strategies and high level of anxiety may cause psychologically based nausea. Thus patients with a high level of anxiety and insufficient coping strategies will have a higher degree of nausea to MTX treatment than other patients.~Perspectives This project will contribute to a greater understanding of MTX-induced intolerance in children with leukemia and JIA. This will also be beneficial for all other children who receive low-dose MTX treatment. The project will optimize the maintenance treatment of childhood leukemia and the treatment of JIA by using patient SNP genotypes to determine who can tolerate MTX and who cannot. Additionally, identify patients where psychological intervention may diminish MTX-induced nausea.~Materials and methods~The study population comprises:~Children diagnosed with ALL in maintenance treatment~Children diagnosed with JIA according to ILAR criteria~For inclusion/exclusion criteria see under Eligibility Criteria. For each patient a list of disease specific characteristics will be noted. The level of MTX-induced intolerance is determined by an electronic nausea-diary for four weeks, containing a faces of nausea scale based on a faces of pain scale (34). The gastrointestinal side effects will further be evaluated by a Methotrexate-Intolerance-Severity-Score questionnaire (MISS) (35).~Pharmacogenetic methods:~Blood samples on each patient will be used to determine the prevalence of SNPs in genes encoding MTX-related transporter proteins (genes including: SLCO1B1, SLC19A1, ABCC2, ABCB1). The genetic analysis will be performed at the Institute of Biomedicine, Aarhus University. Genotyping are carried out using the Sequenom MassARRAY Genotyping system (Sequenom, San Diego, CA). In brief multiplex PCR are performed in 5 μl reactions containing 10 ng of genomic DNA, 1.25 x PCR buffer, 0.5 mM dNTP, 100nM of each primer and 0.5U Taq polymerase using standard cycling conditions. The PCR products are then treated with SAP and the probe extension reaction (iPLEX) carried according to the iPLEX standard protocol (Sequenom). The desalted samples are analyzed using a Bruker matrix assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometer (Sequenom) and the genotypes determined using the MassARRAY Typer 3.4 software (Sequenom). The blood sample will also be used to measure the concentration of MTX-polyglutamates in the erythrocytes (Ery-MTX-PG). The measurement of Ery-MTX-PG will be performed by HPLC-technique at the children's oncology lab, Rigshospitalet, Copenhagen, Denmark.~2) Psychological methods: The patients' coping strategies will be investigated using a nausea-coping-questionnaire developed from a pain-coping questionnaire, which has specifically been developed for children and previously been translated to Danish, validated and used in earlier studies. It consists of eight subscales of main coping strategies: Information seeking, problem solving, seeking social support, positive self-statements, behavioral distraction, cognitive distraction, externalizing and internalizing/catastrophizing (36,37,39,40). The patients' level of anxiety will be assessed by Beck Youth Inventories (BYI), which previously have been translated into Danish and validated. The BYI is brief and easy to use. It consists of 20 sentences that investigate fear, worrying and physiological symptoms associated with anxiety (38).~Statistics Power calculation: This is based on the primary target measure (the degree of nausea) quantified by the faces of nausea scale in the nausea diary. The scale has the end points: no nausea and extreme nausea, in numbers 0 to 5. Results from an earlier study using the faces of pain scale show that mean scores were 0.74 (SD=0.70) and 0.91(SD=0.86) (36). From a clinical assessment the investigators expect the mean nausea score for the group of JIA patients to be 2.5 and 1 for the ALL patients. The standard deviation is expected to be similar to the study above (SD=0.9). If the level of significance (alpha) is 0.05, the power is 80% and the ratio between the group sizes is 2, then the calculated size of the study population will be 10 patients in the JIA group and 5 in the ALL group. If the mean nausea score only is 2 for the group of JIA patients, but still 1 for the group of ALL patients, and the standard deviation is greater than expected, SD=2. But alpha still is 0.05, the power is 80%, and the ratio between the group sizes is still 2. Then the calculated size of the study population will be 96 patients in the JIA group and 48 in the ALL group.~Research Plan~The research group consists of:~From Department of Pediatrics, Aarhus University Hospital Skejby:~Main applicant: Nini Kyvsgaard Brix Nørgaard, PhD-student (enrolled at Aarhus University), M.D.~Main supervisor: Troels Herlin, Professor, DMSc; Co-supervisor: Torben Stamm Mikkelsen, MD, PhD.~From Institute of Biomedicine, Aarhus University:~Co-supervisor: Thomas Juhl Corydon, Associate Professor, PhD, Deputy Head of Institute for Biomedicine, Aarhus University.~From Institute for Psychology, Aarhus University:~Co-Supervisor: Mikael Thastum, Professor, PhD, Head of Clinical Psychology, Aarhus University.~The PhD-student will perform and coordinate the daily execution of the project with guidance from the group of supervisors. The first and second year of the project will be dedicated to the collection of patient data and blood samples. Firstly, the inclusion of the JIA patients will commence. Then the inclusion of the ALL patients. The third year will be dedicated to analysis of gene polymorphisms and MTX levels, data analysis and compilation of manuscripts for publication. The research group has extensive research experience and clinical expertise within this area.~Feasibility The laboratory facilities to take the blood samples and carry out the initial handling of them are available. The final analysis will be performed as specified under 'pharmacogenetic methods'. The investigators have access to software to perform the questionnaires electronically, as well as access to statistical support.
|
Role of Pharmacogenetic and Psychological Factors in Methotrexate Tolerance: Studies in Children With Chronic Arthritis and Children With Leukemia
|
Juvenile Idiopathic Arthritis, ALL
|
Inclusion Criteria:~children diagnosed with JIA according to ILAR criteria, whom are followed at the departments of pediatrics at Aarhus University Hospital Skejby and Odense University Hospital.~and children diagnosed with ALL, whom are followed at the departments of pediatrics at Aarhus University Hospital Skejby, Aalborg University Hospital, Odense University Hospital and Rigshospitalet.~aged 9 years and above~currently treated with low-dose MTX for at least six weeks~Exclusion Criteria:~Children with cognitive difficulties will be excluded~Children without ability to speak Danish will be excluded.
|
9 Years
|
19 Years
|
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Methotrexate-induced Nausea | faces nausea scale in the nausea diary | after project year 2 there will be final data analysis |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Methotrexate Intolerance | Methotrexate Intolerance Severity Score by Bulatovic et al (see citation list) | after project year 2 there will be final data analysis |
|
Methotrexate
|
Arthritis, Arthritis, Juvenile, Joint Diseases, Musculoskeletal Diseases, Rheumatic Diseases, Connective Tissue Diseases, Autoimmune Diseases, Immune System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| JIA patients<br>observationational study including children diagnosed with JIA. Patients aged 9 years and above, whom are treated with low-dose MTX may be included. | |
| ALL patients<br>observationational study including children diagnosed with ALL. Patients aged 9 years and above, whom are in maintenance treatment with low-dose MTX may be included. | |
|
Understanding Methotrexate Induced Gastrointestinal Intolerance in Juvenile Idiopathic Arthritis and Childhood Leukemia
Study Overview
=================
Brief Summary
-----------------
Methotrexate is a cornerstone in the treatment of childhood leukemia. When given in high-dose as part of the initial phase of treatment, gastrointestinal toxicity is a known problem. However when children reach maintenance treatment with low-dose methotrexate this is not described as a significant challenge. Children with juvenile idiopathic arthritis are another patient group receiving low-dose methotrexate. Among these patients gastrointestinal intolerance is such a significant problem that treatment may be ceased. The aim of this project is to create a greater understanding of gastrointestinal intolerance associated to low-dose methotrexate treatment by investigating the differences between these two patient groups, investigating genetic and psychological factors.
Detailed Description
-----------------
Background: Childhood leukemia (Acute Lymphoblastic Leukemia, ALL) is the most frequent malignancy in the pediatric population (1). Survival rates have reached above 85% due to advances in chemotherapy. High-dose methotrexate (MTX) is a mainstay in the treatment of ALL (2-4). Gastrointestinal toxicity is a well known challenge associated to high-dose MTX treatment (5). However this is not described as a significant problem among these children when they reach maintenance treatment and receive low-dose MTX treatment. Children with Juvenile Idiopathic Arthritis (JIA) also receive low-dose MTX treatment. Among these patients MTX induced gastrointestinal intolerance is a significant problem. Studies have shown that more than half of the JIA patients have problems tolerating MTX because of nausea which may lead to cessation of treatment (6,7). It is largely unknown why MTX causes nausea but both pharmacogenetic and psychological factors are thought to play a role (8). JIA is the most common chronic pediatric rheumatic disease. Without treatment the disease causes significant short- and long-term disability and quality of life impairment. Prognosis has greatly improved within recent years as a result of substantial progress in disease management and MTX is a mainstay in the treatment of JIA (9-13). The aim of this project is to create a greater understanding of MTX induced gastrointestinal intolerance among children with leukemia and children with JIA. The project will focus on nausea and investigate the level of nausea in the two patient groups and compare if a difference does exist. The investigators will further investigate pharmacogenetic and psychological factors and their relation to the patients' level of nausea. Pharmacogenetic background: MTX is absorbed from the gastrointestinal tract and transported to the bloodstream by transporter proteins in the enterocytes. Elimination of MTX is primarily renal but a percentage of MTX passes through enterohepatic circulation first (14,15). Studies on the use of high-dose MTX treatment to children with ALL suggest that fast hepatic clearance of MTX increases the degree of gastrointestinal toxicity. It has further been shown that patients with mutations (Single Nucleotide Peptides, SNPs) in the gene encoding the hepatic transporter protein SLCO1B1, responsible for transporting MTX into the liver, have less gastrointestinal toxicity to high-dose MTX (16). The transporter protein encoded by SLC19A1 is placed both in the liver and the enterocytes (15). Studies on adult patients diagnosed with either psoriasis or rheumatoid arthritis and treated with low-dose MTX, and studies on ALL patients in high-dose MTX show that SLC19A1 is associated to the concentration of MTX in plasma and erythrocytes as well as MTX-related toxicity (1,17-20). Transporter proteins that transport MTX out of the liver and into the bile ducts are encoded by ABCC2 and ABCB1(15). Studies on adult patients with rheumatoid arthritis in low-dose MTX, adults with Chronic Myeloid Leukemia and studies on ALL patients in high-dose MTX have shown that both genes are pharmacokinetically important and ABCC2 has further been shown associated to MTX-related gastrointestinal toxicity (5,21-24). Previous studies on patients with rheumatoid arthritis, childhood leukemia and JIA have shown that the frequency of clinically relevant SNPs in genes encoding MTX-related transporter proteins are: SLCO1B1 (70.3%), ABCB1 (20.6%), ABCC2 (56.8%), SLC19A1 (31%) (5,16,17,19,21,25-28).The investigators therefore believe it conceivable to find the selected genetic polymorphisms for MTX-related transporter proteins in the participating study population. Pharmocogenetic Aims: Investigate if MTX-related gastrointestinal intolerance is associated to the enterohepatic circulation. Specifically, to determine if SNPs in genes encoding MTX-related liver transporter proteins are associated to the level of drug induced gastrointestinal side effects. Pharmacogenetic Hypotheses: Patients with SNPs in genes encoding MTX-related transporter proteins in the liver have a lower level of enterohepatic circulation of MTX and thus have a lower level of nausea than other patients. Psychological Background: Studies on adult cancer patients have shown that psychologically based nausea occurring after treatment with chemotherapy is a possible explanation for the nausea which is out of proportion with the medicine's emetogenic potential. It is also a possible explanation for the great variation in the level of cancer patients' nausea after the same type of chemotherapy (29,30). Studies on children in chemotherapy for different cancers have shown that psychological factors, such as coping strategies and anxiety, affect the degree of chemotherapy associated nausea and vomiting (31-33). The investigators want to investigate if this is also the case for children with leukemia in maintenance treatment with low-dose MTX as well as JIA patients in low-dose MTX-treatment. Psychological aims: To investigate if the nausea-coping strategies and anxiety level of the study population are associated to the degree of MTX-induced gastrointestinal intolerance. And investigate if there is a difference between the two patient groups. Psychological hypotheses: Insufficient psychological coping strategies and high level of anxiety may cause psychologically based nausea. Thus patients with a high level of anxiety and insufficient coping strategies will have a higher degree of nausea to MTX treatment than other patients. Perspectives This project will contribute to a greater understanding of MTX-induced intolerance in children with leukemia and JIA. This will also be beneficial for all other children who receive low-dose MTX treatment. The project will optimize the maintenance treatment of childhood leukemia and the treatment of JIA by using patient SNP genotypes to determine who can tolerate MTX and who cannot. Additionally, identify patients where psychological intervention may diminish MTX-induced nausea. Materials and methods The study population comprises: Children diagnosed with ALL in maintenance treatment Children diagnosed with JIA according to ILAR criteria For inclusion/exclusion criteria see under Eligibility Criteria. For each patient a list of disease specific characteristics will be noted. The level of MTX-induced intolerance is determined by an electronic nausea-diary for four weeks, containing a faces of nausea scale based on a faces of pain scale (34). The gastrointestinal side effects will further be evaluated by a Methotrexate-Intolerance-Severity-Score questionnaire (MISS) (35). Pharmacogenetic methods: Blood samples on each patient will be used to determine the prevalence of SNPs in genes encoding MTX-related transporter proteins (genes including: SLCO1B1, SLC19A1, ABCC2, ABCB1). The genetic analysis will be performed at the Institute of Biomedicine, Aarhus University. Genotyping are carried out using the Sequenom MassARRAY Genotyping system (Sequenom, San Diego, CA). In brief multiplex PCR are performed in 5 μl reactions containing 10 ng of genomic DNA, 1.25 x PCR buffer, 0.5 mM dNTP, 100nM of each primer and 0.5U Taq polymerase using standard cycling conditions. The PCR products are then treated with SAP and the probe extension reaction (iPLEX) carried according to the iPLEX standard protocol (Sequenom). The desalted samples are analyzed using a Bruker matrix assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometer (Sequenom) and the genotypes determined using the MassARRAY Typer 3.4 software (Sequenom). The blood sample will also be used to measure the concentration of MTX-polyglutamates in the erythrocytes (Ery-MTX-PG). The measurement of Ery-MTX-PG will be performed by HPLC-technique at the children's oncology lab, Rigshospitalet, Copenhagen, Denmark. 2) Psychological methods: The patients' coping strategies will be investigated using a nausea-coping-questionnaire developed from a pain-coping questionnaire, which has specifically been developed for children and previously been translated to Danish, validated and used in earlier studies. It consists of eight subscales of main coping strategies: Information seeking, problem solving, seeking social support, positive self-statements, behavioral distraction, cognitive distraction, externalizing and internalizing/catastrophizing (36,37,39,40). The patients' level of anxiety will be assessed by Beck Youth Inventories (BYI), which previously have been translated into Danish and validated. The BYI is brief and easy to use. It consists of 20 sentences that investigate fear, worrying and physiological symptoms associated with anxiety (38). Statistics Power calculation: This is based on the primary target measure (the degree of nausea) quantified by the faces of nausea scale in the nausea diary. The scale has the end points: no nausea and extreme nausea, in numbers 0 to 5. Results from an earlier study using the faces of pain scale show that mean scores were 0.74 (SD=0.70) and 0.91(SD=0.86) (36). From a clinical assessment the investigators expect the mean nausea score for the group of JIA patients to be 2.5 and 1 for the ALL patients. The standard deviation is expected to be similar to the study above (SD=0.9). If the level of significance (alpha) is 0.05, the power is 80% and the ratio between the group sizes is 2, then the calculated size of the study population will be 10 patients in the JIA group and 5 in the ALL group. If the mean nausea score only is 2 for the group of JIA patients, but still 1 for the group of ALL patients, and the standard deviation is greater than expected, SD=2. But alpha still is 0.05, the power is 80%, and the ratio between the group sizes is still 2. Then the calculated size of the study population will be 96 patients in the JIA group and 48 in the ALL group. Research Plan The research group consists of: From Department of Pediatrics, Aarhus University Hospital Skejby: Main applicant: Nini Kyvsgaard Brix Nørgaard, PhD-student (enrolled at Aarhus University), M.D. Main supervisor: Troels Herlin, Professor, DMSc; Co-supervisor: Torben Stamm Mikkelsen, MD, PhD. From Institute of Biomedicine, Aarhus University: Co-supervisor: Thomas Juhl Corydon, Associate Professor, PhD, Deputy Head of Institute for Biomedicine, Aarhus University. From Institute for Psychology, Aarhus University: Co-Supervisor: Mikael Thastum, Professor, PhD, Head of Clinical Psychology, Aarhus University. The PhD-student will perform and coordinate the daily execution of the project with guidance from the group of supervisors. The first and second year of the project will be dedicated to the collection of patient data and blood samples. Firstly, the inclusion of the JIA patients will commence. Then the inclusion of the ALL patients. The third year will be dedicated to analysis of gene polymorphisms and MTX levels, data analysis and compilation of manuscripts for publication. The research group has extensive research experience and clinical expertise within this area. Feasibility The laboratory facilities to take the blood samples and carry out the initial handling of them are available. The final analysis will be performed as specified under 'pharmacogenetic methods'. The investigators have access to software to perform the questionnaires electronically, as well as access to statistical support.
Official Title
-----------------
Role of Pharmacogenetic and Psychological Factors in Methotrexate Tolerance: Studies in Children With Chronic Arthritis and Children With Leukemia
Conditions
-----------------
Juvenile Idiopathic Arthritis, ALL
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: children diagnosed with JIA according to ILAR criteria, whom are followed at the departments of pediatrics at Aarhus University Hospital Skejby and Odense University Hospital. and children diagnosed with ALL, whom are followed at the departments of pediatrics at Aarhus University Hospital Skejby, Aalborg University Hospital, Odense University Hospital and Rigshospitalet. aged 9 years and above currently treated with low-dose MTX for at least six weeks Exclusion Criteria: Children with cognitive difficulties will be excluded Children without ability to speak Danish will be excluded.
Ages Eligible for Study
-----------------
Minimum Age: 9 Years
Maximum Age: 19 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| JIA patients<br>observationational study including children diagnosed with JIA. Patients aged 9 years and above, whom are treated with low-dose MTX may be included. | |
| ALL patients<br>observationational study including children diagnosed with ALL. Patients aged 9 years and above, whom are in maintenance treatment with low-dose MTX may be included. | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Methotrexate-induced Nausea | faces nausea scale in the nausea diary | after project year 2 there will be final data analysis |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Methotrexate Intolerance | Methotrexate Intolerance Severity Score by Bulatovic et al (see citation list) | after project year 2 there will be final data analysis |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Methotrexate
|
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NCT00886366
|
Single Ascending Dose Study With Healthy Male Volunteers and Type II Diabetic Patients
|
The purpose of this study is to assess safety and tolerability of AZD6714 after single ascending oral doses in healthy male subjects and type 2 diabetic patients.
|
A Randomised, Single-Blind, Placebo-Controlled, Single-Centre, Phase I Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Interaction After Single Ascending Oral Doses of AZD6714 in Healthy Male Volunteers and Male Type II Diabetic Patients
|
Type 2 Diabetes
|
* Drug: AZD6714
* Drug: Placebo
* Drug: AZD6714
* Drug: AZD6714
|
Inclusion Criteria:~Part A,Healthy male subjects, aged between ≥20 and ≤40 years.~Part B,Male T2DM patients, aged between ≥20 and ≤65 years. Treatment with metformin as single therapy for T2DM for at least 30 days prior to enrollment~Exclusion Criteria:~Part A,Clin sign illness or clin relevant trauma, as judged by the investigator, within 2 weeks before the first administration of the IP.~Part A Clin sign abnormalities in clinical chemistry, haematology, or urinalysis results as judged by the investigator~Part B, History of ischemic heart disease, symptomatic heart failure, stroke, transitory ischemic attack or symptomatic peripheral vascular disease.~Any clinically significant abnormality identified on physical examination, laboratory tests or ECG, which in the judgment of the investigator would compromise the patient's safety or successful participation.
|
20 Years
|
40 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety variables (AE, BP, pulse, plasma glucose, laboratory variables and ECG) | | AEs will be collected during the whole study period (1-3 months). The other variables will be measured repeatedly during 24 hours on the study day sessions |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic variables | | Blood samples taken repeatedly during 24 hours on study day sessions. |
| Pharmacodynamic variables (P-Glucose, S-Insulin and C-peptide) | | Blood samples taken repeatedly during 24 hours on study day sessions. |
|
Type II Diabetes
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>AZD6714 in 8 increasing oral single doses a-h given to 8 groups (3 on active and 1 on placebo in each group) | Drug: AZD6714<br>* Oral single doses a-h suspension<br>Drug: Placebo<br>* Oral single doses suspension<br>|
| Experimental: 2<br>2 oral single doses d and g suspensions of AZD6714 given to 2 groups (3+1) together with food | Drug: Placebo<br>* Oral single doses suspension<br>Drug: AZD6714<br>* Oral single doses d and g suspension<br>|
| Experimental: 3<br>Two increasing oral doses of AZD6714 and one placebo given to 2 groups with 3 type 2 diabetic patients. | Drug: Placebo<br>* Oral single doses suspension<br>Drug: AZD6714<br>* Oral single doses a-d suspension<br>|
|
Single Ascending Dose Study With Healthy Male Volunteers and Type II Diabetic Patients
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess safety and tolerability of AZD6714 after single ascending oral doses in healthy male subjects and type 2 diabetic patients.
Official Title
-----------------
A Randomised, Single-Blind, Placebo-Controlled, Single-Centre, Phase I Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Interaction After Single Ascending Oral Doses of AZD6714 in Healthy Male Volunteers and Male Type II Diabetic Patients
Conditions
-----------------
Type 2 Diabetes
Intervention / Treatment
-----------------
* Drug: AZD6714
* Drug: Placebo
* Drug: AZD6714
* Drug: AZD6714
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Part A,Healthy male subjects, aged between ≥20 and ≤40 years. Part B,Male T2DM patients, aged between ≥20 and ≤65 years. Treatment with metformin as single therapy for T2DM for at least 30 days prior to enrollment Exclusion Criteria: Part A,Clin sign illness or clin relevant trauma, as judged by the investigator, within 2 weeks before the first administration of the IP. Part A Clin sign abnormalities in clinical chemistry, haematology, or urinalysis results as judged by the investigator Part B, History of ischemic heart disease, symptomatic heart failure, stroke, transitory ischemic attack or symptomatic peripheral vascular disease. Any clinically significant abnormality identified on physical examination, laboratory tests or ECG, which in the judgment of the investigator would compromise the patient's safety or successful participation.
Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 40 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>AZD6714 in 8 increasing oral single doses a-h given to 8 groups (3 on active and 1 on placebo in each group) | Drug: AZD6714<br>* Oral single doses a-h suspension<br>Drug: Placebo<br>* Oral single doses suspension<br>|
| Experimental: 2<br>2 oral single doses d and g suspensions of AZD6714 given to 2 groups (3+1) together with food | Drug: Placebo<br>* Oral single doses suspension<br>Drug: AZD6714<br>* Oral single doses d and g suspension<br>|
| Experimental: 3<br>Two increasing oral doses of AZD6714 and one placebo given to 2 groups with 3 type 2 diabetic patients. | Drug: Placebo<br>* Oral single doses suspension<br>Drug: AZD6714<br>* Oral single doses a-d suspension<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety variables (AE, BP, pulse, plasma glucose, laboratory variables and ECG) | | AEs will be collected during the whole study period (1-3 months). The other variables will be measured repeatedly during 24 hours on the study day sessions |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic variables | | Blood samples taken repeatedly during 24 hours on study day sessions. |
| Pharmacodynamic variables (P-Glucose, S-Insulin and C-peptide) | | Blood samples taken repeatedly during 24 hours on study day sessions. |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Type II Diabetes
|
||
NCT01324856
|
Pancreaticogastrostomy Versus Pancreaticojejunostomy in Reconstruction After Cephalic Duodenopancreatectomy
|
Pancreaticoduodenectomy is the standards surgical procedure for various malignant and benign disease of the pancreas and periampullariy region. During the recent years, mortality rate of pancreaticoduodenectomy has decreased to 5% in specialized centers. Although, this procedure still carries considerable morbidity up to 40%, depending of definition of complications. Pancreatic fistula remains a common complication and the main cause of other morbidities and mortality. Pancreaticojejunal (PJ) anastomosis is the most often used method of reconstruction after pancreaticoduodenectomy. Several technique modifications such as placement of the stents, reinforcement of anasomosis with fibrin glue, pancreatic duct occlusion and pancreaticogastrostomy (PG) type of anastomosis was used in order to decrease pancreatic fistula rate. Since, some retrospective studies showed better results with some technique, several meta-analyses did not show any advantage of those various modifications. It was shown that the higher risk of pancreatic fistula was noticed in patients with soft residual pancreas and small diameter of pancreatic duct. There is only one randomized study in the literature dealing with this problem. This study did not reveal any significant differences between PG and PJ in patients with soft pancreas and small duct. In order to investigate once more this important issue, the researchers conducted randomized multicenter controlled trial.
|
Results of Pancreaticogastrostomy Versus Pancreaticojejunostomy in Reconstruction After Cephalic Duodenopancreatectomy in Patients With Soft Pancreas and Small Pancreatic Duct
|
Pancreatic Cancer, Pancreatic Anastomotic Leak
|
* Procedure: Pancreatico gastro anastomosis
* Procedure: Pancreaticojejuno anastomosis
|
Inclusion Criteria:~Patients undergone cephalic duodenopanceatectomy~soft pancreas~small diameter of the pancreatic remnant~Exclusion Criteria:~Age bellow 18 and under 80~prevous pancreatic surgery~pregnancy~Psychosis
|
18 Years
|
80 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| abdominal complications | Abdominal complications comprises: Pancreatic fistula, acute fluid collection, acute pancreatitis, billiay fistula, gastric fistula, enteral distula, hemorrhage and delayed gastric emptying | 2 years |
|
pancreatic cancer, periampulary cancer, pancreaticogastro vs pancreaticojejuno anastomosis
|
Pancreatic Neoplasms, Anastomotic Leak, Digestive System Neoplasms, Neoplasms by Site, Neoplasms, Endocrine Gland Neoplasms, Digestive System Diseases, Pancreatic Diseases, Endocrine System Diseases, Postoperative Complications, Pathologic Processes
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pancreaticogastro anastomosis<br> | Procedure: Pancreatico gastro anastomosis<br>* After the pylorus preserving cephalic pancreaticoduodenectomy, pancreatico gasto teremino-lateral anastomosis will be performed. The anastomosis will be done with posterior wall of the stomach. Pancreas will be mobilized at least 5 cm, two tobaco stiches will be applied on posterior wall of the stomach and hole of 2 cm will be done in the middle. Anterior wall of the stomach will be opened, for easier placement of the pancreas in to the stomach cavity. Pancreas will be entered in the stomach trough , tobacco stitches tided and just 2 or 3 stitches will be applied on the stomach mucosa and pancreatic capsule. After that classic hepatico jejuno and antecolic duodeno jejuno anatomosis will ber performed.<br>|
| Active Comparator: Pancreaticojejuno anastomosis<br> | Procedure: Pancreaticojejuno anastomosis<br>* After the pylorus preserving cephalic pancreaticoduodenectomy, pancreatico jejuno termino lateral duct to mucosa anastomosis will be performed. After that classic hepatico jejuno and antecolic duodeno jejuno anatomosis will ber performed.<br>|
|
Pancreaticogastrostomy Versus Pancreaticojejunostomy in Reconstruction After Cephalic Duodenopancreatectomy
Study Overview
=================
Brief Summary
-----------------
Pancreaticoduodenectomy is the standards surgical procedure for various malignant and benign disease of the pancreas and periampullariy region. During the recent years, mortality rate of pancreaticoduodenectomy has decreased to 5% in specialized centers. Although, this procedure still carries considerable morbidity up to 40%, depending of definition of complications. Pancreatic fistula remains a common complication and the main cause of other morbidities and mortality. Pancreaticojejunal (PJ) anastomosis is the most often used method of reconstruction after pancreaticoduodenectomy. Several technique modifications such as placement of the stents, reinforcement of anasomosis with fibrin glue, pancreatic duct occlusion and pancreaticogastrostomy (PG) type of anastomosis was used in order to decrease pancreatic fistula rate. Since, some retrospective studies showed better results with some technique, several meta-analyses did not show any advantage of those various modifications. It was shown that the higher risk of pancreatic fistula was noticed in patients with soft residual pancreas and small diameter of pancreatic duct. There is only one randomized study in the literature dealing with this problem. This study did not reveal any significant differences between PG and PJ in patients with soft pancreas and small duct. In order to investigate once more this important issue, the researchers conducted randomized multicenter controlled trial.
Official Title
-----------------
Results of Pancreaticogastrostomy Versus Pancreaticojejunostomy in Reconstruction After Cephalic Duodenopancreatectomy in Patients With Soft Pancreas and Small Pancreatic Duct
Conditions
-----------------
Pancreatic Cancer, Pancreatic Anastomotic Leak
Intervention / Treatment
-----------------
* Procedure: Pancreatico gastro anastomosis
* Procedure: Pancreaticojejuno anastomosis
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients undergone cephalic duodenopanceatectomy soft pancreas small diameter of the pancreatic remnant Exclusion Criteria: Age bellow 18 and under 80 prevous pancreatic surgery pregnancy Psychosis
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pancreaticogastro anastomosis<br> | Procedure: Pancreatico gastro anastomosis<br>* After the pylorus preserving cephalic pancreaticoduodenectomy, pancreatico gasto teremino-lateral anastomosis will be performed. The anastomosis will be done with posterior wall of the stomach. Pancreas will be mobilized at least 5 cm, two tobaco stiches will be applied on posterior wall of the stomach and hole of 2 cm will be done in the middle. Anterior wall of the stomach will be opened, for easier placement of the pancreas in to the stomach cavity. Pancreas will be entered in the stomach trough , tobacco stitches tided and just 2 or 3 stitches will be applied on the stomach mucosa and pancreatic capsule. After that classic hepatico jejuno and antecolic duodeno jejuno anatomosis will ber performed.<br>|
| Active Comparator: Pancreaticojejuno anastomosis<br> | Procedure: Pancreaticojejuno anastomosis<br>* After the pylorus preserving cephalic pancreaticoduodenectomy, pancreatico jejuno termino lateral duct to mucosa anastomosis will be performed. After that classic hepatico jejuno and antecolic duodeno jejuno anatomosis will ber performed.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| abdominal complications | Abdominal complications comprises: Pancreatic fistula, acute fluid collection, acute pancreatitis, billiay fistula, gastric fistula, enteral distula, hemorrhage and delayed gastric emptying | 2 years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
pancreatic cancer, periampulary cancer, pancreaticogastro vs pancreaticojejuno anastomosis
|
||
NCT05001256
|
Determination of Physical Activity Status and Adherence to the Mediterranean Diet in Adults and Related Health Outcomes
|
A physically active life with adequate and balanced nutrition is essential for a healthy life. Unhealthy diet and being physically inactive are among the common risk factors that need to be corrected in order to maintain and improve health. The Mediterranean diet, first described by Angel Keys, is rich in plant foods such as grains, fruits, vegetables, legumes, oilseeds and olives; The main source of added oils is olive oil; moderate-high consumption of fish and seafood, moderate-level consumption of eggs, poultry and dairy products, and low-level red meat; It is a nutrition model with moderate intake of wine / fermented beverages (such as turnip, grape juice). Preferring vegetable oils instead of animal fats, preferring fish instead of red meat consumption, preferring low-fat / fat-free milk and dairy products, limiting the intake of simple sugar and refined carbohydrates, fruit rich in fiber and antioxidants in the Mediterranean diet, which is shown as an example of healthy nutrition today. It is thought that this type of nutrition can prevent the formation of chronic diseases due to features such as increasing vegetable consumption.~Determining the nutritional status and physical activity levels of individuals and their associated health outcomes; It is very important in terms of determining the current situation and determining the priority problems that need to be solved.
|
A physically active life with adequate and balanced nutrition is essential for a healthy life. Unhealthy diet and being physically inactive are among the common risk factors that need to be corrected in order to maintain and improve health. In a cohort study of seven countries (USA, Finland, the Netherlands, Italy, the former Yugoslavia, Greece, and Japan) based on 25 years of follow-up and examining the relationship between dietary behaviors and mortality due to coronary heart disease, lower cardiovascular mortality rates were observed among participating countries in the Mediterranean region. . This has been attributed to traditional dietary behaviors such as high olive oil consumption in Greece, high fish consumption in Dalmatia (Croatia) and high vegetable consumption in Italy. Preferring vegetable oils instead of animal fats, preferring fish instead of red meat consumption, preferring low-fat/fat-free milk and dairy products, limiting simple sugar and refined carbohydrate intake, fruit rich in fiber and antioxidants in the Mediterranean diet, which is shown as an example of healthy nutrition today. It is thought that this type of nutrition can prevent the formation of chronic diseases due to the features such as increasing vegetable consumption. It is reported that low physical activity levels increase the risk of chronic diseases. Studies have shown that adherence to the Mediterranean diet is associated with lower BMI, total fat, and abdominal adiposity. It is also known that a decrease in body total fat rate is observed with physical activity. In addition, BMI values decrease with physical activity. With the changes in lifestyle habits in recent years, societies are moving away from the Mediterranean type of diet and becoming more and more sedentary. For this reason, it is very important to determine the current situation regarding the health outcomes related to the nutritional status and physical activity levels of the individuals, to determine the priority problems that need to be solved, and to raise the awareness of the society on this issue.~The aim of this study is to determine the adherence to the Mediterranean diet, physical activity status and related health outcomes of adult individuals who applied to the physical therapy outpatient clinic of a private hospital.
|
Determination of Physical Activity Status and Adherence to the Mediterranean Diet in Adults and Related Health Outcomes
|
Obesity, Nutrition, Physical Activity, Chronic Disease, Mediterranean Diet
|
* Other: questionnaire study
|
Inclusion Criteria:~be between the ages of 18-65 having applied to the physical therapy outpatient clinic voluntarily agree to participate in research~Exclusion Criteria:~be under the age of 18 be over 65
|
18 Years
|
65 Years
|
All
| null |
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mediterranean Diet Compliance Scale (MEDAS) | The 14-item Mediterranean Diet Adaptation Scale (MEDAS) will be used to determine the adaptation status of individuals to the Mediterranean diet. In the scale of adaptation to the Mediterranean diet, there are a total of 14 questions, 12 of which are about food consumption frequency and 2 are about food consumption habits. The score given for each question is 0 or 1 point. Then the scores are summed and the score is evaluated as ≤5 (low agreement), 6-9 (moderate agreement) and ≥10 (high agreement). | at baseline |
| International Physical Activity Questionnaire (IPAQ) | The International Physical Activity Questionnaire (IPAQ) will be used to examine physical activity status. According to the IPAQ form, in which daily activities are evaluated as sitting, walking, moderate and vigorous activities and questioning the activity status in the past week, individuals are grouped as inactive (<600met), minimally active (600-3000met) and active (>3000met) according to their IPAQ scores. | at baseline |
| obesity | Body mass index will be calculated by taking the person's height and body weight information.~Waist and hip circumference measurements will also be made. | at baseline |
| chronic disease | 79 / 5000 Çeviri sonuçları Participants will be asked about the presence of a chronic disease diagnosed by the physician. | at baseline |
|
obesity, mediterranean diet, physical activity, chronic diseases
|
Chronic Disease, Disease Attributes, Pathologic Processes
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| All Participants<br>Individuals between the ages of 18-65 who applied to the physical therapy and rehabilitation outpatient clinic of a private hospital and voluntarily agreed to participate in the study will be included in the study. Written consent will be obtained from the participants.~Participants' information will be recorded on a pre-prepared questionnaire containing structured questions. Questionnaire questioning will be applied to individuals through face-to-face interviews. The questionnaire form consists of three parts: 1. Sociodemographic characteristics, 2. Mediterranean Diet Adherence Scale (MEDAS), 3. International Physical Activity Questionnaire (IPAQ). | Other: questionnaire study<br>* Participants will be surveyed through face-to-face interviews.<br>|
|
Determination of Physical Activity Status and Adherence to the Mediterranean Diet in Adults and Related Health Outcomes
Study Overview
=================
Brief Summary
-----------------
A physically active life with adequate and balanced nutrition is essential for a healthy life. Unhealthy diet and being physically inactive are among the common risk factors that need to be corrected in order to maintain and improve health. The Mediterranean diet, first described by Angel Keys, is rich in plant foods such as grains, fruits, vegetables, legumes, oilseeds and olives; The main source of added oils is olive oil; moderate-high consumption of fish and seafood, moderate-level consumption of eggs, poultry and dairy products, and low-level red meat; It is a nutrition model with moderate intake of wine / fermented beverages (such as turnip, grape juice). Preferring vegetable oils instead of animal fats, preferring fish instead of red meat consumption, preferring low-fat / fat-free milk and dairy products, limiting the intake of simple sugar and refined carbohydrates, fruit rich in fiber and antioxidants in the Mediterranean diet, which is shown as an example of healthy nutrition today. It is thought that this type of nutrition can prevent the formation of chronic diseases due to features such as increasing vegetable consumption. Determining the nutritional status and physical activity levels of individuals and their associated health outcomes; It is very important in terms of determining the current situation and determining the priority problems that need to be solved.
Detailed Description
-----------------
A physically active life with adequate and balanced nutrition is essential for a healthy life. Unhealthy diet and being physically inactive are among the common risk factors that need to be corrected in order to maintain and improve health. In a cohort study of seven countries (USA, Finland, the Netherlands, Italy, the former Yugoslavia, Greece, and Japan) based on 25 years of follow-up and examining the relationship between dietary behaviors and mortality due to coronary heart disease, lower cardiovascular mortality rates were observed among participating countries in the Mediterranean region. . This has been attributed to traditional dietary behaviors such as high olive oil consumption in Greece, high fish consumption in Dalmatia (Croatia) and high vegetable consumption in Italy. Preferring vegetable oils instead of animal fats, preferring fish instead of red meat consumption, preferring low-fat/fat-free milk and dairy products, limiting simple sugar and refined carbohydrate intake, fruit rich in fiber and antioxidants in the Mediterranean diet, which is shown as an example of healthy nutrition today. It is thought that this type of nutrition can prevent the formation of chronic diseases due to the features such as increasing vegetable consumption. It is reported that low physical activity levels increase the risk of chronic diseases. Studies have shown that adherence to the Mediterranean diet is associated with lower BMI, total fat, and abdominal adiposity. It is also known that a decrease in body total fat rate is observed with physical activity. In addition, BMI values decrease with physical activity. With the changes in lifestyle habits in recent years, societies are moving away from the Mediterranean type of diet and becoming more and more sedentary. For this reason, it is very important to determine the current situation regarding the health outcomes related to the nutritional status and physical activity levels of the individuals, to determine the priority problems that need to be solved, and to raise the awareness of the society on this issue. The aim of this study is to determine the adherence to the Mediterranean diet, physical activity status and related health outcomes of adult individuals who applied to the physical therapy outpatient clinic of a private hospital.
Official Title
-----------------
Determination of Physical Activity Status and Adherence to the Mediterranean Diet in Adults and Related Health Outcomes
Conditions
-----------------
Obesity, Nutrition, Physical Activity, Chronic Disease, Mediterranean Diet
Intervention / Treatment
-----------------
* Other: questionnaire study
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: be between the ages of 18-65 having applied to the physical therapy outpatient clinic voluntarily agree to participate in research Exclusion Criteria: be under the age of 18 be over 65
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years
Sexes Eligible for Study
-----------------
All
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| All Participants<br>Individuals between the ages of 18-65 who applied to the physical therapy and rehabilitation outpatient clinic of a private hospital and voluntarily agreed to participate in the study will be included in the study. Written consent will be obtained from the participants. Participants' information will be recorded on a pre-prepared questionnaire containing structured questions. Questionnaire questioning will be applied to individuals through face-to-face interviews. The questionnaire form consists of three parts: 1. Sociodemographic characteristics, 2. Mediterranean Diet Adherence Scale (MEDAS), 3. International Physical Activity Questionnaire (IPAQ). | Other: questionnaire study<br>* Participants will be surveyed through face-to-face interviews.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mediterranean Diet Compliance Scale (MEDAS) | The 14-item Mediterranean Diet Adaptation Scale (MEDAS) will be used to determine the adaptation status of individuals to the Mediterranean diet. In the scale of adaptation to the Mediterranean diet, there are a total of 14 questions, 12 of which are about food consumption frequency and 2 are about food consumption habits. The score given for each question is 0 or 1 point. Then the scores are summed and the score is evaluated as ≤5 (low agreement), 6-9 (moderate agreement) and ≥10 (high agreement). | at baseline |
| International Physical Activity Questionnaire (IPAQ) | The International Physical Activity Questionnaire (IPAQ) will be used to examine physical activity status. According to the IPAQ form, in which daily activities are evaluated as sitting, walking, moderate and vigorous activities and questioning the activity status in the past week, individuals are grouped as inactive (<600met), minimally active (600-3000met) and active (>3000met) according to their IPAQ scores. | at baseline |
| obesity | Body mass index will be calculated by taking the person's height and body weight information. Waist and hip circumference measurements will also be made. | at baseline |
| chronic disease | 79 / 5000 Çeviri sonuçları Participants will be asked about the presence of a chronic disease diagnosed by the physician. | at baseline |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
obesity, mediterranean diet, physical activity, chronic diseases
|
||
NCT00852995
|
Dose Finding Study of HP802-247 in Venous Leg Ulcers
|
This is a 16-week study for subjects with a venous leg ulcer between the knee and ankle. This research is being done to determine the effectiveness of two dosing frequencies and two different concentrations of HP802-247, together with standard care, compared to placebo, plus standard care.
|
A Phase II Randomized, Double Blind, Placebo Controlled Dose Finding Study Investigating the Efficacy of HP802-247 in Venous Leg Ulcers
|
Venous Leg Ulcer, Venous Stasis Ulcers
|
* Biological: HP802-247
* Biological: Placebo (Vehicle)
|
Inclusion Criteria:~Provide informed consent.~Willing to comply with protocol instructions, including allowing all study assessments.~Have a venous leg ulcer (venous etiology)between the knee and ankle, at or above the malleolus.~Venous insufficiency confirmed by duplex Doppler ultrasound examination for valvular or venous incompetence.~Target ulcer duration greater than or equal to 6 weeks but less than or equal to 24 months.~Exclusion Criteria:~Women who are pregnant or lactating~Therapy with another investigational agent within thirty (30) days of Screening, or during the study.~A target ulcer of non-venous etiologies.~Refusal of or inability to tolerate compression therapy.~Therapy of the target ulcer with tissue-engineered cell-based skin equivalents within 30 days preceding the Screening Visit.~Therapy of the target ulcer with topical growth factors within 1 week preceding the Screening Visit.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Average Percent (%) Change From Baseline in the Target Wound Area in Each Treatment Group Over the Twelve-week Double-blind Treatment Period. | For each treatment group the area of each subject's target ulcer was measured on a weekly basis, for up to 12 weeks, or until wound closure, whichever occurred first, using a laser-based wound imaging system in conjunction with software to measure area. An average of the 12 measurements were assessed. | Weekly, over the 12 week treatment period, or until wound closure, which ever occurred first |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kaplan-Meier Probability of Non-Closure | This key secondary outcome was the days to wound closure based on a Kaplan-Meier survival analysis. | 14 weeks - the final visit for one subject was delayed by two weeks |
| Percent of Change From Baseline in Target Wound Area at Each of the Twelve Double-blind Treatment Weeks. | For each treatment group the area of each subject's target ulcer was measured on a weekly basis, for up to 12 weeks, using a laser-based wound imaging system in conjunction with software to measure area. | Weekly, over the 12 week treatment period, or until wound closure, which ever occurred first |
| Proportion of Subjects Achieving ≥ 50% Decrease in Target Wound Area From Baseline Through Week 13 | The area of each subject's target wound was measured at each visit and the proportion of subjects with a decrease in area from baseline ≥ 50% was calculated for each treatment group. | Over the 12 week treatment period or until the wound closed, which ever occurred first. |
| Percentage of Participants With Complete Wound Closure at Each Visit | Treatment groups were compared for the proportion of wounds closed at each weekly visit. For subjects who dropped from the study, their remaining visit values were imputed using LOCF. | Weekly, over the 12 week treatment period |
| Target Ulcer Pain Was Measured Using a Visual Analog Scale [Range: 0mm - 100mm]. Subjects Marked Their Pain Level on a 100 mm Horizontal Line, With a Short Vertical Line Across the Scale, 0 Denoting no Pain and 100mm the Maximum Pain. | Target ulcer pain was measured using a Visual Analog Scale [Range: 0mm - 100mm]. Subjects marked their pain level on a 100 mm horizontal line, with a short vertical line across the scale, 0 denoting no pain and 100mm the maximum pain. Each weekly measurement is reported as the average of all subjects scores at each week per treatment group. | Weekly, over the 12 week treatment period |
| Median Time to Achieve Complete Wound Closure, Based on Based on a Kaplan-Meier Survival Analysis, Over the 12-Week Treatment Period From Baseline. | This key secondary outcome was the days to wound closure based on a Kaplan-Meier survival analysis. | 14 weeks - the final visit for one subject was delayed by two weeks |
|
Venous Leg Ulcer (VLU), Venous Stasis Ulcer (VSU), VLU, VSU, Leg Ulcer, Leg Wound
|
Varicose Ulcer, Leg Ulcer, Ulcer, Pathologic Processes, Skin Ulcer, Skin Diseases, Varicose Veins, Vascular Diseases, Cardiovascular Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A - Low Q7D<br>Low dose HP802-247, applied at each visit | Biological: HP802-247<br>* One dose of HP802-247 consists of 260 microliters (uL) containing keratinocytes and fibroblasts totaling 0.5 x 10-6 power or 5.0 x 10-6 power cells per mL, plus fibrin.<br>|
| Experimental: B - Low Q14D<br>Low dose HP802-247 applied at Visits 1, 3, 5, 7, 9, 11 and Placebo at Visits 2, 4, 6, 8, 10, and 12 | Biological: HP802-247<br>* One dose of HP802-247 consists of 260 microliters (uL) containing keratinocytes and fibroblasts totaling 0.5 x 10-6 power or 5.0 x 10-6 power cells per mL, plus fibrin.<br>|
| Experimental: C - High Q7D<br>High dose HP802-247, applied at each visit | Biological: HP802-247<br>* One dose of HP802-247 consists of 260 microliters (uL) containing keratinocytes and fibroblasts totaling 0.5 x 10-6 power or 5.0 x 10-6 power cells per mL, plus fibrin.<br>|
| Experimental: D - High Q14D<br>High dose HP802-247, applied at Visits 1, 3, 5, 7, 9, 11 and Placebo at Visits 2, 4, 6, 8, 10, and 12 | Biological: HP802-247<br>* One dose of HP802-247 consists of 260 microliters (uL) containing keratinocytes and fibroblasts totaling 0.5 x 10-6 power or 5.0 x 10-6 power cells per mL, plus fibrin.<br>|
| Placebo Comparator: E - Vehicle<br>Placebo (Vehicle), applied at each visit | Biological: Placebo (Vehicle)<br>* Placebo (Vehicle) consisting of:~Component 1 - acellular fibrinogen solution; Component 2 - acellular thrombin solution<br>|
|
Dose Finding Study of HP802-247 in Venous Leg Ulcers
Study Overview
=================
Brief Summary
-----------------
This is a 16-week study for subjects with a venous leg ulcer between the knee and ankle. This research is being done to determine the effectiveness of two dosing frequencies and two different concentrations of HP802-247, together with standard care, compared to placebo, plus standard care.
Official Title
-----------------
A Phase II Randomized, Double Blind, Placebo Controlled Dose Finding Study Investigating the Efficacy of HP802-247 in Venous Leg Ulcers
Conditions
-----------------
Venous Leg Ulcer, Venous Stasis Ulcers
Intervention / Treatment
-----------------
* Biological: HP802-247
* Biological: Placebo (Vehicle)
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Provide informed consent. Willing to comply with protocol instructions, including allowing all study assessments. Have a venous leg ulcer (venous etiology)between the knee and ankle, at or above the malleolus. Venous insufficiency confirmed by duplex Doppler ultrasound examination for valvular or venous incompetence. Target ulcer duration greater than or equal to 6 weeks but less than or equal to 24 months. Exclusion Criteria: Women who are pregnant or lactating Therapy with another investigational agent within thirty (30) days of Screening, or during the study. A target ulcer of non-venous etiologies. Refusal of or inability to tolerate compression therapy. Therapy of the target ulcer with tissue-engineered cell-based skin equivalents within 30 days preceding the Screening Visit. Therapy of the target ulcer with topical growth factors within 1 week preceding the Screening Visit.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A - Low Q7D<br>Low dose HP802-247, applied at each visit | Biological: HP802-247<br>* One dose of HP802-247 consists of 260 microliters (uL) containing keratinocytes and fibroblasts totaling 0.5 x 10-6 power or 5.0 x 10-6 power cells per mL, plus fibrin.<br>|
| Experimental: B - Low Q14D<br>Low dose HP802-247 applied at Visits 1, 3, 5, 7, 9, 11 and Placebo at Visits 2, 4, 6, 8, 10, and 12 | Biological: HP802-247<br>* One dose of HP802-247 consists of 260 microliters (uL) containing keratinocytes and fibroblasts totaling 0.5 x 10-6 power or 5.0 x 10-6 power cells per mL, plus fibrin.<br>|
| Experimental: C - High Q7D<br>High dose HP802-247, applied at each visit | Biological: HP802-247<br>* One dose of HP802-247 consists of 260 microliters (uL) containing keratinocytes and fibroblasts totaling 0.5 x 10-6 power or 5.0 x 10-6 power cells per mL, plus fibrin.<br>|
| Experimental: D - High Q14D<br>High dose HP802-247, applied at Visits 1, 3, 5, 7, 9, 11 and Placebo at Visits 2, 4, 6, 8, 10, and 12 | Biological: HP802-247<br>* One dose of HP802-247 consists of 260 microliters (uL) containing keratinocytes and fibroblasts totaling 0.5 x 10-6 power or 5.0 x 10-6 power cells per mL, plus fibrin.<br>|
| Placebo Comparator: E - Vehicle<br>Placebo (Vehicle), applied at each visit | Biological: Placebo (Vehicle)<br>* Placebo (Vehicle) consisting of: Component 1 - acellular fibrinogen solution; Component 2 - acellular thrombin solution<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Average Percent (%) Change From Baseline in the Target Wound Area in Each Treatment Group Over the Twelve-week Double-blind Treatment Period. | For each treatment group the area of each subject's target ulcer was measured on a weekly basis, for up to 12 weeks, or until wound closure, whichever occurred first, using a laser-based wound imaging system in conjunction with software to measure area. An average of the 12 measurements were assessed. | Weekly, over the 12 week treatment period, or until wound closure, which ever occurred first |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kaplan-Meier Probability of Non-Closure | This key secondary outcome was the days to wound closure based on a Kaplan-Meier survival analysis. | 14 weeks - the final visit for one subject was delayed by two weeks |
| Percent of Change From Baseline in Target Wound Area at Each of the Twelve Double-blind Treatment Weeks. | For each treatment group the area of each subject's target ulcer was measured on a weekly basis, for up to 12 weeks, using a laser-based wound imaging system in conjunction with software to measure area. | Weekly, over the 12 week treatment period, or until wound closure, which ever occurred first |
| Proportion of Subjects Achieving ≥ 50% Decrease in Target Wound Area From Baseline Through Week 13 | The area of each subject's target wound was measured at each visit and the proportion of subjects with a decrease in area from baseline ≥ 50% was calculated for each treatment group. | Over the 12 week treatment period or until the wound closed, which ever occurred first. |
| Percentage of Participants With Complete Wound Closure at Each Visit | Treatment groups were compared for the proportion of wounds closed at each weekly visit. For subjects who dropped from the study, their remaining visit values were imputed using LOCF. | Weekly, over the 12 week treatment period |
| Target Ulcer Pain Was Measured Using a Visual Analog Scale [Range: 0mm - 100mm]. Subjects Marked Their Pain Level on a 100 mm Horizontal Line, With a Short Vertical Line Across the Scale, 0 Denoting no Pain and 100mm the Maximum Pain. | Target ulcer pain was measured using a Visual Analog Scale [Range: 0mm - 100mm]. Subjects marked their pain level on a 100 mm horizontal line, with a short vertical line across the scale, 0 denoting no pain and 100mm the maximum pain. Each weekly measurement is reported as the average of all subjects scores at each week per treatment group. | Weekly, over the 12 week treatment period |
| Median Time to Achieve Complete Wound Closure, Based on Based on a Kaplan-Meier Survival Analysis, Over the 12-Week Treatment Period From Baseline. | This key secondary outcome was the days to wound closure based on a Kaplan-Meier survival analysis. | 14 weeks - the final visit for one subject was delayed by two weeks |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Venous Leg Ulcer (VLU), Venous Stasis Ulcer (VSU), VLU, VSU, Leg Ulcer, Leg Wound
|
|
NCT02761278
|
Expression of HOXA10 and HOXA11 in the Endometrium of Infertility Patients With an Endometrial Polyp Before and After Polypectomy
|
The aim of this study is to measure the expression of HOXA10 and HOXA11 in the endometrium of infertility patients with an endometrial polyp before and after polypectomy. HOXA10 and HOXA11 are well-established markers of implantation. It is uncertain as to whether an endometrial polyp interferes with embryo implantation. A higher expression of HOXA10 and HOXA11 after polypectomy can indicate that endometrial polyp does interfere with embryo implantation.
| null |
Infertility
|
* Procedure: Endometrial biopsy
|
Inclusion Criteria:~Infertile women with endometrial polyp~Exclusion Criteria:~Endometriosis~Polycystic ovary syndrome~Hydrosalpinx~Sub-mucus myoma~Women who have taken hormonal therapy in the preceding month
|
20 Years
|
40 Years
|
Female
|
No
|
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of amounts of HOXA10 and HOXA11 expressed before and after polypectomy | | Four months |
|
Infertility, Genital Diseases, Urogenital Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: HOXA10 and HOXA11 Expression Before Polypectomy<br>A biopsy will taken in infertility patients with endometrial polyp before polypectomy | Procedure: Endometrial biopsy<br> <br> |
| Active Comparator: HOXA10 and HOXA11 Expression After Polypectomy<br>A biopsy will taken in infertility patients with endometrial polyp 1-3 months after polypectomy | Procedure: Endometrial biopsy<br> <br> |
|
Expression of HOXA10 and HOXA11 in the Endometrium of Infertility Patients With an Endometrial Polyp Before and After Polypectomy
Study Overview
=================
Brief Summary
-----------------
The aim of this study is to measure the expression of HOXA10 and HOXA11 in the endometrium of infertility patients with an endometrial polyp before and after polypectomy. HOXA10 and HOXA11 are well-established markers of implantation. It is uncertain as to whether an endometrial polyp interferes with embryo implantation. A higher expression of HOXA10 and HOXA11 after polypectomy can indicate that endometrial polyp does interfere with embryo implantation.
Conditions
-----------------
Infertility
Intervention / Treatment
-----------------
* Procedure: Endometrial biopsy
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Infertile women with endometrial polyp Exclusion Criteria: Endometriosis Polycystic ovary syndrome Hydrosalpinx Sub-mucus myoma Women who have taken hormonal therapy in the preceding month
Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 40 Years
Sexes Eligible for Study
-----------------
Female
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: HOXA10 and HOXA11 Expression Before Polypectomy<br>A biopsy will taken in infertility patients with endometrial polyp before polypectomy | Procedure: Endometrial biopsy<br> <br> |
| Active Comparator: HOXA10 and HOXA11 Expression After Polypectomy<br>A biopsy will taken in infertility patients with endometrial polyp 1-3 months after polypectomy | Procedure: Endometrial biopsy<br> <br> |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of amounts of HOXA10 and HOXA11 expressed before and after polypectomy | | Four months |
|
|||
NCT05064943
|
Reliability and Validity of the 2-Minute Step Test in Patients With Knee Arthroplasty
|
Total knee arthroplasty (TKA) is a cost-effective treatment for end-stage knee osteoarthritis. It has demonstrable benefits such as reducing pain and improving activity and quality of life. Despite the decrease in pain after surgery, the expectations of patients regarding their physical functions are not fully realized. Physical performance tests and reporting tests are used to objectively evaluate physical function and reveal the patient's condition. It is known that physical performance tests better reflect post-surgical changes. In addition, it has been stated that there may be serious differences between the results of the reports based tests and the actual functional capacities of the patients. The 2-minute walk test and the 6-minute walk test are tests that are used in the evaluation of lower extremity physical performance and have been shown to be valid and reliable in different populations. However, a certain length of corridor is needed in order to carry out these timed walking tests. As an alternative to these, another test used in the evaluation of physical performance is the 2-minute step test. This test, which was developed in 1999, does not require much equipment and space, so the test can be easily applied in any environment. In this test, a height specific to each individual is determined (as high from the ground as the distance between the Spina iliaca anterior superior and the midpoint of the patella), and the participant is asked to raise and lower both knees, respectively, to this height for 2 minutes. These tests used in the evaluation of patients should be valid, reliable and sensitive. In clinical studies, reliability is an important psychometric property. Because stable data are necessary to provide accurate data on treatment effects or the amount of change observed over time. Another important psychometric property is validity. Validity is defined as the degree to which a concept is accurately measured in a quantitative study. Reliability studies of the 2-minute step test in active and sedentary lean adults have been conducted, but the psychometric evaluations necessary for its routine use in patients with TDP have not been performed.
|
This study is a non-experimental, descriptive methodological study. Forty-nine patients who applied to the outpatient clinic of Kütahya Health Sciences University, Evliya Çelebi Training and Research Hospital due to knee osteoarthritis, will included in the study. Pre-study power analysis was performed and the power to detect clinically significant difference was calculated as 90% (5% Type I error level). The smallest sample size to be taken was determined by using the sample size creation section in the G-Power (version 3.0.10) program.
|
Reliability and Validity of the 2-Minute Step Test in Patients With Knee Arthroplasty
|
Total Knee Replacement, Reliability and Validity
|
* Diagnostic Test: 2-minute step test
|
Inclusion Criteria:~Being 18 years or older~Having been diagnosed with knee OA by an orthopedic specialist and having a knee prosthesis applied.~Exclusion Criteria:~Those who do not understand verbal and written information in Turkish~Patients who underwent complex surgery requiring bone grafting~Those with orthopedic or neurological disease causing gait disturbance~Those with pain of 5 or more on the numerical pain scale~Those with a history of Myocardial Infarction~Those who have undergone surgery in the last 6 months~Those with concomitant heart failure~Those with unstable angina~Those with uncontrolled hypertension~Those with severe COPD, Asthma and Interstitial Lung Disease
|
18 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital for Special Surgery Knee-Rating Scale | The Hospital for Special Surgery knee-rating scale was developed to be used as a standardized tool to measure outcomes in patients with osteoarthritis and knee arthroplasty. The scale can be used to evaluate the patient before surgery and to monitor knee function after surgery. Hospital for Special Surgery knee rating scale is widely used in the clinic by physiotherapists and orthopaedic surgeons. | Baseline |
| Numerical Pain Scale | The pain levels of the patients will be determined using the Numerical Pain Scale (NPS). This scale is a score containing values between 0-10 on a 10 cm horizontal line. In scoring, 0 points indicates the absence of pain, while 10 points means unbearable pain. Patients are asked to mark the part that is equivalent to their own pain on the 10 cm line. Thus, the pain level of the patients is determined. | Baseline |
| 2-Minute Step Test | The participant stands and counts for 2 minutes. The minimum height to raise the knee is determined for each participant by calculating the midpoint between the patella and the anterior superior iliac spine. They are instructed to complete as many steps as possible during the 2-minute period. A verbal command is given every 30 seconds to encourage performance: You're doing great, keep it up. If the claudication symptom becomes unbearable, the patient can stop during the test, but the time is not stopped. Patients who discontinue testing due to symptoms of claudication are encouraged to return to testing as soon as possible. An evaluator records the number of steps in the right leg. | Baseline |
| 6-Minute Walking Test | The participant is asked to walk as far as possible along a 30-meter straight corridor in a 6-minute period. Running is not allowed. The evaluator gives the standard incentive you are doing well, keep going every minute during the test. The distance traveled in 6 minutes is recorded in meters. | Baseline |
| 2-Minute Walk Test | Participants are asked to walk within 2 minutes along a 30 m indoor corridor. They are not allowed to talk while walking. The distance walked is recorded in meters. | Baseline |
| 2-Minute Step Test | The participant stands and counts for 2 minutes. The minimum height to raise the knee is determined for each participant by calculating the midpoint between the patella and the anterior superior iliac spine. They are instructed to complete as many steps as possible during the 2-minute period. A verbal command is given every 30 seconds to encourage performance: You're doing great, keep it up. If the claudication symptom becomes unbearable, the patient can stop during the test, but the time is not stopped. Patients who discontinue testing due to symptoms of claudication are encouraged to return to testing as soon as possible. An evaluator records the number of steps in the right leg. | Within same day after the baseline |
|
Total Knee Replacement, Step Test
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Total Knee Replacement<br>Patients who have undergone total knee replacement | Diagnostic Test: 2-minute step test<br>* The participant stands and counts for 2 minutes. The minimum height to raise the knee is determined for each participant by calculating the midpoint between the patella and the anterior superior iliac spine. They are instructed to complete as many steps as possible during the 2-minute period. A verbal command is given every 30 seconds to encourage performance: You're doing great, keep it up. If the claudication symptom becomes unbearable, the patient can stop during the test, but the time is not stopped. Patients who discontinue testing due to symptoms of claudication are encouraged to return to testing as soon as possible. An evaluator records the number of steps in the right leg.<br>|
|
Reliability and Validity of the 2-Minute Step Test in Patients With Knee Arthroplasty
Study Overview
=================
Brief Summary
-----------------
Total knee arthroplasty (TKA) is a cost-effective treatment for end-stage knee osteoarthritis. It has demonstrable benefits such as reducing pain and improving activity and quality of life. Despite the decrease in pain after surgery, the expectations of patients regarding their physical functions are not fully realized. Physical performance tests and reporting tests are used to objectively evaluate physical function and reveal the patient's condition. It is known that physical performance tests better reflect post-surgical changes. In addition, it has been stated that there may be serious differences between the results of the reports based tests and the actual functional capacities of the patients. The 2-minute walk test and the 6-minute walk test are tests that are used in the evaluation of lower extremity physical performance and have been shown to be valid and reliable in different populations. However, a certain length of corridor is needed in order to carry out these timed walking tests. As an alternative to these, another test used in the evaluation of physical performance is the 2-minute step test. This test, which was developed in 1999, does not require much equipment and space, so the test can be easily applied in any environment. In this test, a height specific to each individual is determined (as high from the ground as the distance between the Spina iliaca anterior superior and the midpoint of the patella), and the participant is asked to raise and lower both knees, respectively, to this height for 2 minutes. These tests used in the evaluation of patients should be valid, reliable and sensitive. In clinical studies, reliability is an important psychometric property. Because stable data are necessary to provide accurate data on treatment effects or the amount of change observed over time. Another important psychometric property is validity. Validity is defined as the degree to which a concept is accurately measured in a quantitative study. Reliability studies of the 2-minute step test in active and sedentary lean adults have been conducted, but the psychometric evaluations necessary for its routine use in patients with TDP have not been performed.
Detailed Description
-----------------
This study is a non-experimental, descriptive methodological study. Forty-nine patients who applied to the outpatient clinic of Kütahya Health Sciences University, Evliya Çelebi Training and Research Hospital due to knee osteoarthritis, will included in the study. Pre-study power analysis was performed and the power to detect clinically significant difference was calculated as 90% (5% Type I error level). The smallest sample size to be taken was determined by using the sample size creation section in the G-Power (version 3.0.10) program.
Official Title
-----------------
Reliability and Validity of the 2-Minute Step Test in Patients With Knee Arthroplasty
Conditions
-----------------
Total Knee Replacement, Reliability and Validity
Intervention / Treatment
-----------------
* Diagnostic Test: 2-minute step test
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Being 18 years or older Having been diagnosed with knee OA by an orthopedic specialist and having a knee prosthesis applied. Exclusion Criteria: Those who do not understand verbal and written information in Turkish Patients who underwent complex surgery requiring bone grafting Those with orthopedic or neurological disease causing gait disturbance Those with pain of 5 or more on the numerical pain scale Those with a history of Myocardial Infarction Those who have undergone surgery in the last 6 months Those with concomitant heart failure Those with unstable angina Those with uncontrolled hypertension Those with severe COPD, Asthma and Interstitial Lung Disease
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Total Knee Replacement<br>Patients who have undergone total knee replacement | Diagnostic Test: 2-minute step test<br>* The participant stands and counts for 2 minutes. The minimum height to raise the knee is determined for each participant by calculating the midpoint between the patella and the anterior superior iliac spine. They are instructed to complete as many steps as possible during the 2-minute period. A verbal command is given every 30 seconds to encourage performance: You're doing great, keep it up. If the claudication symptom becomes unbearable, the patient can stop during the test, but the time is not stopped. Patients who discontinue testing due to symptoms of claudication are encouraged to return to testing as soon as possible. An evaluator records the number of steps in the right leg.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital for Special Surgery Knee-Rating Scale | The Hospital for Special Surgery knee-rating scale was developed to be used as a standardized tool to measure outcomes in patients with osteoarthritis and knee arthroplasty. The scale can be used to evaluate the patient before surgery and to monitor knee function after surgery. Hospital for Special Surgery knee rating scale is widely used in the clinic by physiotherapists and orthopaedic surgeons. | Baseline |
| Numerical Pain Scale | The pain levels of the patients will be determined using the Numerical Pain Scale (NPS). This scale is a score containing values between 0-10 on a 10 cm horizontal line. In scoring, 0 points indicates the absence of pain, while 10 points means unbearable pain. Patients are asked to mark the part that is equivalent to their own pain on the 10 cm line. Thus, the pain level of the patients is determined. | Baseline |
| 2-Minute Step Test | The participant stands and counts for 2 minutes. The minimum height to raise the knee is determined for each participant by calculating the midpoint between the patella and the anterior superior iliac spine. They are instructed to complete as many steps as possible during the 2-minute period. A verbal command is given every 30 seconds to encourage performance: You're doing great, keep it up. If the claudication symptom becomes unbearable, the patient can stop during the test, but the time is not stopped. Patients who discontinue testing due to symptoms of claudication are encouraged to return to testing as soon as possible. An evaluator records the number of steps in the right leg. | Baseline |
| 6-Minute Walking Test | The participant is asked to walk as far as possible along a 30-meter straight corridor in a 6-minute period. Running is not allowed. The evaluator gives the standard incentive you are doing well, keep going every minute during the test. The distance traveled in 6 minutes is recorded in meters. | Baseline |
| 2-Minute Walk Test | Participants are asked to walk within 2 minutes along a 30 m indoor corridor. They are not allowed to talk while walking. The distance walked is recorded in meters. | Baseline |
| 2-Minute Step Test | The participant stands and counts for 2 minutes. The minimum height to raise the knee is determined for each participant by calculating the midpoint between the patella and the anterior superior iliac spine. They are instructed to complete as many steps as possible during the 2-minute period. A verbal command is given every 30 seconds to encourage performance: You're doing great, keep it up. If the claudication symptom becomes unbearable, the patient can stop during the test, but the time is not stopped. Patients who discontinue testing due to symptoms of claudication are encouraged to return to testing as soon as possible. An evaluator records the number of steps in the right leg. | Within same day after the baseline |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Total Knee Replacement, Step Test
|
|||
NCT03732742
|
Comparison of Mid-term Results of Total Correction of TOF Between Preservation of PV and Trans-annular Patch.
|
To compare of mid-term results of total correction of tetralogy of fallot between preservation of pulmonary valve and trans-annular patching , thus avoiding PV regurgitation during TOF repair , this will determine the value of this procedure over trans-annular patching regarding to right ventricular performance.
|
Surgical repair of congenital lesions associated with right ventricular outflow tract obstruction frequently requires the destruction of pulmonary valve (PV) competents including the pulmonary annulas. The resulatnt pulmonary insufficiency may lead to late functional deterioration of right ventricular performance. Acute right ventricular dysfunction has been associated with poor pulmonary runoff, tricuspid valve regurgitaion and pulmonary hypertension. Preservation of PV comptence may prevent both early and late right ventricular failure. Total repair of tetralogy of fallot is a corrective surgical procedure that involves closure of the ventricular septal defect (VSD) and relief of right ventricular outflow tract (RVOT) obstruction. The surgeon must decide whether the right ventricular outflow tract size will be sufficient to allow for the entire cardiac output to traverse it without causing extreme elevation in right ventricular pressure or will go for trans-annular patch. Recently interest has shifted to preserving the integrity of the pulmonary valve annulus thus avoiding pulmonary valve regurgitation.
|
Comparison of Mid-term Results of Total Correction of Tetralogy of Fallot Between Preservation of Pulmonary Valve and Trans-annular Patching
|
Tetrology of Fallot
|
* Procedure: TOF repair with trans-annular patch VS preservation of PV
|
Inclusion Criteria:~Patients undergoing elective total correction of tetralogy of Fallot.~Any age group.~Normal pulmonay branches~Exclusion Criteria:~Patients associated with other congenital anomalies.~Regarding PV morphology, patients with pulmonary atresia , absence of PV.~Patients with anomalous coronary artery anatomy obstructs access to the RV~Extra-cardiac illness that is expected to limit survival to less than 5 years.e.g active hepatitis or significant hepatic or renal disorders.
| null | null |
All
|
No
|
Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gender | Parameters will be measured include gender preoperatively | One week for preoperative assessment. |
| Body weight | Parameters will be measured include body weight in kilograms preoperatively | One week for preoperative assessment. |
| Height | Parameters will be measured include height in meters preoperatively | One week for preoperative assessment. |
| Oxygen saturation , RV function | Parameters will be measured include Oxygen saturation level % , RV function by measure RV fractional area changes (RVFAC) % preoperatively | One week for preoperative assessment. |
| include median RVOT gradient and degree of PV stenosis | Parameters will be measured include median RVOT gradient in mmhg , degree of PV stenosis by peak gradient across the PV in mmhg preoperatively | One week for preoperative assessment. |
| PV annulus and PV z-score | Parameters will be measured include median PV annulus diameter in mm , median PV Z-score diameter in mm preoperatively | One week for preoperative assessment. |
| degree of PV regurge, degree of TR and RV size | Parameters will be measured include degree of PV regurge jet size by color doppler,degree of TR by jet area -central jets in cm^2 , RV size (RV diastolic area in cm^ , RV systolic area in cm^ ) preoperatively | One week for preoperative assessment. |
| Age | Parameters will be measured include age in months preoperatively | One week for preoperative assessment |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gender | Parameters will be measured include gender pre-discharge postoperative assessment. | Pre-discharge postoperative assessment within one month |
| Body weight | Parameters will be measured include body weight in kilograms pre-discharge postoperative assessment. | Pre-discharge postoperative assessment within one month |
| Height | Parameters will be measured include height in meters pre-discharge postoperative assessment. | Pre-discharge postoperative assessment within one month |
| Oxygen saturation , RV function | Parameters will be measured include Oxygen saturation level % , RV function by measure RV fractional area changes (RVFAC) % Pre-discharge postoperative assessment. | Pre-discharge postoperative assessment within one month |
| Median RVOT gradient and degree of PV stenosis | Parameters will be measured include median RVOT gradient in mmhg , degree of PV stenosis by peak gradient across the PV in mmhg pre-discharge postoperative assessment. | Pre-discharge postoperative assessment within one month |
| PV annulus and PV z-score | Parameters will be measured include median PV annulus diameter in mm , median PV Z-score diameter in mm pre-discharge postoperative assessment. | Pre-discharge postoperative assessment within one month |
| degree of PV regurge, degree of TR and RV size | Parameters will be measured include degree of PV regurge jet size by color doppler,degree of TR by jet area -central jets in cm^2 , RV size (RV diastolic area in cm^ , RV systolic area in cm^ ) pre-discharge postoperative assessment. | Pre-discharge postoperative assessment within one month |
| Median cross clamp time and CPB time | Parameters will be measured include Median cross clamp time in minutes and CPB time in minutes pre-discharge postoperative assessment. | Pre-discharge postoperative assessment within one month |
| ICU stay | Parameters will be measured include ICU stay days pre-discharge postoperative assessment. | Pre-discharge postoperative assessment within one month |
| Time till weaning from mechanical ventilator | Parameters will be measured include Time till weaning from mechanical ventilator in hours pre-discharge postoperative assessment. | Pre-discharge postoperative assessment within one month |
| Age | Parameters will be measured include age in months pre-discharge postoperative assessment. | Pre-discharge postoperative assessment within one month |
|
Tetralogy of Fallot, Heart Defects, Congenital, Cardiovascular Abnormalities, Cardiovascular Diseases, Heart Diseases, Congenital Abnormalities
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TOF repair with preservation of PV<br>Surgical intervention by repair of Tetralogy of Fallot with preservation of pulmonary valve, recently interested has shifted to preserving the integrity of the pulmonary valve. | Procedure: TOF repair with trans-annular patch VS preservation of PV<br>* One group study<br>|
| Experimental: TOF repair with trans-annular patch<br>Surgical intervention by repair of Tetralogy of Fallot with trans-annular patch, right ventricular hypertrophy, right ventricular dilatation and pulmonary vavle regurgitation has been recognized as one of the most important risk factors for both right and left ventricular performance after the repair of Tetralogy of Fallot. | Procedure: TOF repair with trans-annular patch VS preservation of PV<br>* One group study<br>|
|
Comparison of Mid-term Results of Total Correction of TOF Between Preservation of PV and Trans-annular Patch.
Study Overview
=================
Brief Summary
-----------------
To compare of mid-term results of total correction of tetralogy of fallot between preservation of pulmonary valve and trans-annular patching , thus avoiding PV regurgitation during TOF repair , this will determine the value of this procedure over trans-annular patching regarding to right ventricular performance.
Detailed Description
-----------------
Surgical repair of congenital lesions associated with right ventricular outflow tract obstruction frequently requires the destruction of pulmonary valve (PV) competents including the pulmonary annulas. The resulatnt pulmonary insufficiency may lead to late functional deterioration of right ventricular performance. Acute right ventricular dysfunction has been associated with poor pulmonary runoff, tricuspid valve regurgitaion and pulmonary hypertension. Preservation of PV comptence may prevent both early and late right ventricular failure. Total repair of tetralogy of fallot is a corrective surgical procedure that involves closure of the ventricular septal defect (VSD) and relief of right ventricular outflow tract (RVOT) obstruction. The surgeon must decide whether the right ventricular outflow tract size will be sufficient to allow for the entire cardiac output to traverse it without causing extreme elevation in right ventricular pressure or will go for trans-annular patch. Recently interest has shifted to preserving the integrity of the pulmonary valve annulus thus avoiding pulmonary valve regurgitation.
Official Title
-----------------
Comparison of Mid-term Results of Total Correction of Tetralogy of Fallot Between Preservation of Pulmonary Valve and Trans-annular Patching
Conditions
-----------------
Tetrology of Fallot
Intervention / Treatment
-----------------
* Procedure: TOF repair with trans-annular patch VS preservation of PV
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients undergoing elective total correction of tetralogy of Fallot. Any age group. Normal pulmonay branches Exclusion Criteria: Patients associated with other congenital anomalies. Regarding PV morphology, patients with pulmonary atresia , absence of PV. Patients with anomalous coronary artery anatomy obstructs access to the RV Extra-cardiac illness that is expected to limit survival to less than 5 years.e.g active hepatitis or significant hepatic or renal disorders.
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TOF repair with preservation of PV<br>Surgical intervention by repair of Tetralogy of Fallot with preservation of pulmonary valve, recently interested has shifted to preserving the integrity of the pulmonary valve. | Procedure: TOF repair with trans-annular patch VS preservation of PV<br>* One group study<br>|
| Experimental: TOF repair with trans-annular patch<br>Surgical intervention by repair of Tetralogy of Fallot with trans-annular patch, right ventricular hypertrophy, right ventricular dilatation and pulmonary vavle regurgitation has been recognized as one of the most important risk factors for both right and left ventricular performance after the repair of Tetralogy of Fallot. | Procedure: TOF repair with trans-annular patch VS preservation of PV<br>* One group study<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gender | Parameters will be measured include gender preoperatively | One week for preoperative assessment. |
| Body weight | Parameters will be measured include body weight in kilograms preoperatively | One week for preoperative assessment. |
| Height | Parameters will be measured include height in meters preoperatively | One week for preoperative assessment. |
| Oxygen saturation , RV function | Parameters will be measured include Oxygen saturation level % , RV function by measure RV fractional area changes (RVFAC) % preoperatively | One week for preoperative assessment. |
| include median RVOT gradient and degree of PV stenosis | Parameters will be measured include median RVOT gradient in mmhg , degree of PV stenosis by peak gradient across the PV in mmhg preoperatively | One week for preoperative assessment. |
| PV annulus and PV z-score | Parameters will be measured include median PV annulus diameter in mm , median PV Z-score diameter in mm preoperatively | One week for preoperative assessment. |
| degree of PV regurge, degree of TR and RV size | Parameters will be measured include degree of PV regurge jet size by color doppler,degree of TR by jet area -central jets in cm^2 , RV size (RV diastolic area in cm^ , RV systolic area in cm^ ) preoperatively | One week for preoperative assessment. |
| Age | Parameters will be measured include age in months preoperatively | One week for preoperative assessment |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gender | Parameters will be measured include gender pre-discharge postoperative assessment. | Pre-discharge postoperative assessment within one month |
| Body weight | Parameters will be measured include body weight in kilograms pre-discharge postoperative assessment. | Pre-discharge postoperative assessment within one month |
| Height | Parameters will be measured include height in meters pre-discharge postoperative assessment. | Pre-discharge postoperative assessment within one month |
| Oxygen saturation , RV function | Parameters will be measured include Oxygen saturation level % , RV function by measure RV fractional area changes (RVFAC) % Pre-discharge postoperative assessment. | Pre-discharge postoperative assessment within one month |
| Median RVOT gradient and degree of PV stenosis | Parameters will be measured include median RVOT gradient in mmhg , degree of PV stenosis by peak gradient across the PV in mmhg pre-discharge postoperative assessment. | Pre-discharge postoperative assessment within one month |
| PV annulus and PV z-score | Parameters will be measured include median PV annulus diameter in mm , median PV Z-score diameter in mm pre-discharge postoperative assessment. | Pre-discharge postoperative assessment within one month |
| degree of PV regurge, degree of TR and RV size | Parameters will be measured include degree of PV regurge jet size by color doppler,degree of TR by jet area -central jets in cm^2 , RV size (RV diastolic area in cm^ , RV systolic area in cm^ ) pre-discharge postoperative assessment. | Pre-discharge postoperative assessment within one month |
| Median cross clamp time and CPB time | Parameters will be measured include Median cross clamp time in minutes and CPB time in minutes pre-discharge postoperative assessment. | Pre-discharge postoperative assessment within one month |
| ICU stay | Parameters will be measured include ICU stay days pre-discharge postoperative assessment. | Pre-discharge postoperative assessment within one month |
| Time till weaning from mechanical ventilator | Parameters will be measured include Time till weaning from mechanical ventilator in hours pre-discharge postoperative assessment. | Pre-discharge postoperative assessment within one month |
| Age | Parameters will be measured include age in months pre-discharge postoperative assessment. | Pre-discharge postoperative assessment within one month |
|
|
NCT04194775
|
A Study of Nofazinlimab (CS1003) in Subjects With Advanced Hepatocellular Carcinoma
|
This is a multi-center, double-blind, randomized, phase III study to investigate the efficacy and safety of Nofazinlimab (CS1003) in combination with lenvatinib and placebo in combination with lenvatinib in the treatment of subjects with no prior systemic treatment and with unresectable advanced hepatocellular carcinoma (HCC). Subjects cannot be eligible for locoregional therapy. In this study, Nofazinlimab (CS1003) (or placebo) and lenvatinib are both considered as the study treatment while Nofazinlimab (CS1003) (or placebo) is the investigational product of and lenvatinib is selected as the basic treatment for HCC.
|
A Multi-Center, Double-Blind, Randomized, Phase III Study to Investigate the Efficacy and Safety of Nofazinlimab (CS1003) in Combination With Lenvatinib Compared to Placebo in Combination With Lenvatinib as First-Line Therapy in Subjects With Advanced Hepatocellular Carcinoma (HCC)
|
Hepatocellular Carcinoma
|
* Drug: Nofazinlimab (CS1003)+Lenvatinib
* Drug: Nofazinlimab (CS1003) Placebo+Lenvatinib
|
Inclusion criteria~Age ≥18 years on the day of signing informed consent-(For Taiwan, the lower limit of age is 20 years).~Subjects with unresectable advanced HCC, that is not eligible for surgery and/or locoregional therapy (Stage B or C based on Barcelona Clinic Liver Cancer [BCLC] staging system, and meets either one of the following criteria: 1) histologically or cytologically confirmed diagnosis of HCC, 2) clinically confirmed diagnosis of HCC according to American Association for the Study of Liver Diseases (AASLD) criteria. Patients without cirrhosis require histological confirmation of diagnosis.~With at least one measurable lesion can be assessed~Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1.~Life expectancy ≥ 3 months.~Child-Pugh A~No prior systemic treatment for advanced HCC~Subjects with hepatitis B virus (HBV) infection, are willing to continue receiving antiviral treatment while on study.~Subjects have adequate organ and marrow function. Female subjects with childbearing potential must have negative serum pregnancy test result at screening. Female subjects with childbearing potential, and male subjects and their female partners with childbearing potential must agree to use an contraceptive method(s) from the day of signing informed consent form (ICF), during the study and till at least 6 months after the last dose of study treatment.~Exclusion criteria~Fibrolamellar-HCC, sarcomatoid, cholangiocellular carcinoma or mixed cholangiocarcinoma and HCC.~A prior bleeding event due to esophageal within 6 months or other gastrointestinal bleeding events within 28 days prior to screening.~Malabsorption syndrome or inability to take oral medication due to other causes.~HBV and HCV co-infection.~Investigator evaluates to increase the drug related risk caused by enrolling subjects in trial and taking study drug, or any serious or uncontrolled systematic disease that confound the drug absorption or the study outcome, e,g diabetes mellitus, hypertension, rheumatoid arthritis, major cardiovascular disease and so on.~Surgery or locoregional therapy for palliative purpose within 4 weeks prior to study treatment.~History of other malignancy(ies) in the past 5 years, except for malignant disease treated with curative intent and without active disease.~Known history of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS).~Current or prior use of systemic corticosteroid (> 10 mg/day prednisone or equivalent) or other immunosuppressive medication within 14 days prior to the first dose of study treatment.~History of bone marrow transplantation or organ transplantation.~History of anaphylaxis or hypersensitivity to any ingredient of the investigational product.~Any contraindication of lenvatinib.~Known history of drugs abuse that would interfere with cooperation with the requirements of the trial.~Pregnant or lactating female subjects.~History of psychiatric disease that would interfere with cooperation with the requirements of the trial; lack of or with restricted physical capability.~QTc interval > 470 msec (as calculated with Fridericia's formula) at screening electrocardiogram (ECG);~Any condition that would in the investigator's judgment, prevent the subject from participating in this study.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | | Expected to be 5.5 years after the first patient is enrollment. |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) assessed by blinded independent central review committee(BICR) | | Expected to be 5.5 years after the first patient is enrollment. |
| Progression-free survival(PFS) assessed by blinded independent central review committee(BICR) based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1 | | Expected to be 5.5 years after the first patient is enrollment. |
| Progression-free survival(PFS) evaluated by investigator based on RECIST v1.1 | | Expected to be 5.5 years after the first patient is enrollment. |
| Objective response rate (ORR) evaluated by investigators based on RECIST v1.1 | | Expected to be 5.5 years after the first patient is enrollment. |
| Duration of response (DoR) evaluated by blinded independent central review committee(BICR) based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1 | | Expected to be 5.5 years after the first patient is enrollment. |
| Duration of response (DoR) evaluated by investigators based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1 | | Expected to be 5.5 years after the first patient is enrollment. |
| Disease control rate (DCR) evaluated by blinded independent central review committee(BICR) based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1 | | Expected to be 5.5 years after the first patient is enrollment. |
| Disease control rate (DCR) evaluated by investigators based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1 | | Expected to be 5.5 years after the first patient is enrollment. |
| Percentage of Participants with Adverse Events | | Expected to be 5.5 years after the first patient is enrollment. |
| Peak and trough serum concentrations of CS1003 | | Expected to be 5.5 years after the first patient is enrollment. |
| Number and percentage of subjects who develop anti-CS1003 antibody (ADA) | | Expected to be 5.5 years after the first patient is enrollment. |
| Time to deterioration (TTD), defined as the time from randomization to the first deterioration of European Organization for the Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) scale | | Expected to be 5.5 years after the first patient is enrollment. |
|
Lenvatinib, Antineoplastic Agents, Protein Kinase Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nofazinlimab (CS1003)<br> | Drug: Nofazinlimab (CS1003)+Lenvatinib<br>* Nofazinlimab (CS1003), intravenous (i.v.) administration every 21 days; Lenvatinib oral administration, once daily<br>|
| Placebo Comparator: Nofazinlimab (CS1003) placebo<br> | Drug: Nofazinlimab (CS1003) Placebo+Lenvatinib<br>* Nofazinlimab (CS1003) Placebo, i.v. administration every 21 days ; Lenvatinib oral administration, once daily<br>|
|
A Study of Nofazinlimab (CS1003) in Subjects With Advanced Hepatocellular Carcinoma
Study Overview
=================
Brief Summary
-----------------
This is a multi-center, double-blind, randomized, phase III study to investigate the efficacy and safety of Nofazinlimab (CS1003) in combination with lenvatinib and placebo in combination with lenvatinib in the treatment of subjects with no prior systemic treatment and with unresectable advanced hepatocellular carcinoma (HCC). Subjects cannot be eligible for locoregional therapy. In this study, Nofazinlimab (CS1003) (or placebo) and lenvatinib are both considered as the study treatment while Nofazinlimab (CS1003) (or placebo) is the investigational product of and lenvatinib is selected as the basic treatment for HCC.
Official Title
-----------------
A Multi-Center, Double-Blind, Randomized, Phase III Study to Investigate the Efficacy and Safety of Nofazinlimab (CS1003) in Combination With Lenvatinib Compared to Placebo in Combination With Lenvatinib as First-Line Therapy in Subjects With Advanced Hepatocellular Carcinoma (HCC)
Conditions
-----------------
Hepatocellular Carcinoma
Intervention / Treatment
-----------------
* Drug: Nofazinlimab (CS1003)+Lenvatinib
* Drug: Nofazinlimab (CS1003) Placebo+Lenvatinib
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria Age ≥18 years on the day of signing informed consent-(For Taiwan, the lower limit of age is 20 years). Subjects with unresectable advanced HCC, that is not eligible for surgery and/or locoregional therapy (Stage B or C based on Barcelona Clinic Liver Cancer [BCLC] staging system, and meets either one of the following criteria: 1) histologically or cytologically confirmed diagnosis of HCC, 2) clinically confirmed diagnosis of HCC according to American Association for the Study of Liver Diseases (AASLD) criteria. Patients without cirrhosis require histological confirmation of diagnosis. With at least one measurable lesion can be assessed Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1. Life expectancy ≥ 3 months. Child-Pugh A No prior systemic treatment for advanced HCC Subjects with hepatitis B virus (HBV) infection, are willing to continue receiving antiviral treatment while on study. Subjects have adequate organ and marrow function. Female subjects with childbearing potential must have negative serum pregnancy test result at screening. Female subjects with childbearing potential, and male subjects and their female partners with childbearing potential must agree to use an contraceptive method(s) from the day of signing informed consent form (ICF), during the study and till at least 6 months after the last dose of study treatment. Exclusion criteria Fibrolamellar-HCC, sarcomatoid, cholangiocellular carcinoma or mixed cholangiocarcinoma and HCC. A prior bleeding event due to esophageal within 6 months or other gastrointestinal bleeding events within 28 days prior to screening. Malabsorption syndrome or inability to take oral medication due to other causes. HBV and HCV co-infection. Investigator evaluates to increase the drug related risk caused by enrolling subjects in trial and taking study drug, or any serious or uncontrolled systematic disease that confound the drug absorption or the study outcome, e,g diabetes mellitus, hypertension, rheumatoid arthritis, major cardiovascular disease and so on. Surgery or locoregional therapy for palliative purpose within 4 weeks prior to study treatment. History of other malignancy(ies) in the past 5 years, except for malignant disease treated with curative intent and without active disease. Known history of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS). Current or prior use of systemic corticosteroid (> 10 mg/day prednisone or equivalent) or other immunosuppressive medication within 14 days prior to the first dose of study treatment. History of bone marrow transplantation or organ transplantation. History of anaphylaxis or hypersensitivity to any ingredient of the investigational product. Any contraindication of lenvatinib. Known history of drugs abuse that would interfere with cooperation with the requirements of the trial. Pregnant or lactating female subjects. History of psychiatric disease that would interfere with cooperation with the requirements of the trial; lack of or with restricted physical capability. QTc interval > 470 msec (as calculated with Fridericia's formula) at screening electrocardiogram (ECG); Any condition that would in the investigator's judgment, prevent the subject from participating in this study.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nofazinlimab (CS1003)<br> | Drug: Nofazinlimab (CS1003)+Lenvatinib<br>* Nofazinlimab (CS1003), intravenous (i.v.) administration every 21 days; Lenvatinib oral administration, once daily<br>|
| Placebo Comparator: Nofazinlimab (CS1003) placebo<br> | Drug: Nofazinlimab (CS1003) Placebo+Lenvatinib<br>* Nofazinlimab (CS1003) Placebo, i.v. administration every 21 days ; Lenvatinib oral administration, once daily<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | | Expected to be 5.5 years after the first patient is enrollment. |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) assessed by blinded independent central review committee(BICR) | | Expected to be 5.5 years after the first patient is enrollment. |
| Progression-free survival(PFS) assessed by blinded independent central review committee(BICR) based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1 | | Expected to be 5.5 years after the first patient is enrollment. |
| Progression-free survival(PFS) evaluated by investigator based on RECIST v1.1 | | Expected to be 5.5 years after the first patient is enrollment. |
| Objective response rate (ORR) evaluated by investigators based on RECIST v1.1 | | Expected to be 5.5 years after the first patient is enrollment. |
| Duration of response (DoR) evaluated by blinded independent central review committee(BICR) based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1 | | Expected to be 5.5 years after the first patient is enrollment. |
| Duration of response (DoR) evaluated by investigators based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1 | | Expected to be 5.5 years after the first patient is enrollment. |
| Disease control rate (DCR) evaluated by blinded independent central review committee(BICR) based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1 | | Expected to be 5.5 years after the first patient is enrollment. |
| Disease control rate (DCR) evaluated by investigators based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1 | | Expected to be 5.5 years after the first patient is enrollment. |
| Percentage of Participants with Adverse Events | | Expected to be 5.5 years after the first patient is enrollment. |
| Peak and trough serum concentrations of CS1003 | | Expected to be 5.5 years after the first patient is enrollment. |
| Number and percentage of subjects who develop anti-CS1003 antibody (ADA) | | Expected to be 5.5 years after the first patient is enrollment. |
| Time to deterioration (TTD), defined as the time from randomization to the first deterioration of European Organization for the Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) scale | | Expected to be 5.5 years after the first patient is enrollment. |
|
||
NCT01629771
|
Disability and Quality of Life in Patients With Lymphatic Filariasis in Rural Southern India
|
According to the World Health Organization, lymphatic filariasis, a mosquito-borne parasitic disease, is the second leading cause of disability worldwide. Across 81 countries, approximately 120 million people are infected with the disease, and of those infected, an estimated 40% reside in India alone. The most disfiguring symptoms of lymphatic filariasis, elephantiasis and lymphedema, cause long-term suffering in patients who are then often embarrassed or even rejected from their communities. Because of the disease's debilitating physical and social effects on patients, this study will explore the intersection of disability and health-related quality of life (HRQoL) in lymphatic filariasis patients in India. Specifically, HRQoL and disability in lymphatic filariasis subjects and age- and gender- matched control subjects will be compared. Two HRQoL tools , the general Dermatology Life Quality Index (DLQI) and a disease-specific instrument developed by a dermatology group in India will be used to gauge HRQol. In addition, the demographic and disease-specific factors associated with HRQoL and disability in filarial lymphedema subjects will be identified.
|
Disability and Quality of Life in Patients With Lymphatic Filariasis in Rural Southern India
|
Lymphatic Filariasis
|
Case Inclusion Criteria~Subjects with a clinical diagnosis of lymphatic filariasis~Subjects over the age of 18 and able to give consent~Case Exclusion Criteria~Subjects on active treatment for lymphatic filariasis~Subjects who are under the age of 18 or unable to give informed consent~Control Inclusion Criteria~Subjects without a clinical diagnosis of lymphatic filariasis~Subjects over the age of 18 and able to give consent~Control Exclusion Criteria~Subjects without a clinical diagnosis of lymphatic filariasis~Subjects who are under the age of 18 or unable to give informed consent
|
18 Years
| null |
All
|
Accepts Healthy Volunteers
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dermatology Life Quality Index (DLQI) Domain Scores | The DLQI is a 10-item questionnaire measuring skin-specific quality of life through six domains: Symptoms & Feelings, Daily Activities, Leisure, Work & School, Personal Relationships, and Treatment. Symptoms & Feelings, Daily Activities, Leisure, and Personal Relationships are each scored from 0 to 3, where 0 is associated with no effect on a patient's life, and 3 is associated with a large effect on a patient's life. Work & School and Treatment are each scored from 0 to 3, where 0 is associated with no effect on a patient's life, and 6 is associated with a large effect on a patient's life. | Assessed after enrollment |
| Lymphatic Filariasis-Specific Quality of Life (LFSQQ) Domain Scores | The LFSQQ was developed to assess quality of life in subjects with lymphatic filariasis through seven domains: Mobility, Self-Care, Usual Activities, Disease Burden, Pain/Discomfort, Psychological Health, and Social Participation. Items are scored on a 5-point scale (no problem, mild, moderate, severe, most severe), and scores for each domain are calculated based on the number of questions answered and the raw scores. Scores for each domain range from 0 to 100, where 0 is associated with a worse quality of life and 100 is associated with a better quality of life. | Assessed after enrollment |
| World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) Domain Scores | The WHODAS 2.0 is a generic health and disability assessment tool that describes effects of disease on six domains: Cognition, Mobility, Self-Care, Getting Along, Life Activities, and Participation in Society. Responses are measured on a 5-point scale from 1 (no difficulty) to 5 (extreme difficulty or cannot do). Scores are calculated using a WHO SPSS 36 version syntax for employed subjects and a WHO SPSS 32 version syntax for unemployed subjects. Scores for each domain range from 0 to 100, where 0 is associated with no impairment of health status, and 100 is associated with a greater impairment of health status. | Assessed after enrollment |
|
Filariasis, Elephantiasis, Filarial, Elephantiasis, Spirurida Infections, Secernentea Infections, Nematode Infections, Helminthiasis, Parasitic Diseases, Infections, Lymphedema, Lymphatic Diseases, Vector Borne Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Lymphatic Filariasis<br> | |
| Patients without Lymphatic Filariasis<br> | |
|
Disability and Quality of Life in Patients With Lymphatic Filariasis in Rural Southern India
Study Overview
=================
Brief Summary
-----------------
According to the World Health Organization, lymphatic filariasis, a mosquito-borne parasitic disease, is the second leading cause of disability worldwide. Across 81 countries, approximately 120 million people are infected with the disease, and of those infected, an estimated 40% reside in India alone. The most disfiguring symptoms of lymphatic filariasis, elephantiasis and lymphedema, cause long-term suffering in patients who are then often embarrassed or even rejected from their communities. Because of the disease's debilitating physical and social effects on patients, this study will explore the intersection of disability and health-related quality of life (HRQoL) in lymphatic filariasis patients in India. Specifically, HRQoL and disability in lymphatic filariasis subjects and age- and gender- matched control subjects will be compared. Two HRQoL tools , the general Dermatology Life Quality Index (DLQI) and a disease-specific instrument developed by a dermatology group in India will be used to gauge HRQol. In addition, the demographic and disease-specific factors associated with HRQoL and disability in filarial lymphedema subjects will be identified.
Official Title
-----------------
Disability and Quality of Life in Patients With Lymphatic Filariasis in Rural Southern India
Conditions
-----------------
Lymphatic Filariasis
Participation Criteria
=================
Eligibility Criteria
-----------------
Case Inclusion Criteria Subjects with a clinical diagnosis of lymphatic filariasis Subjects over the age of 18 and able to give consent Case Exclusion Criteria Subjects on active treatment for lymphatic filariasis Subjects who are under the age of 18 or unable to give informed consent Control Inclusion Criteria Subjects without a clinical diagnosis of lymphatic filariasis Subjects over the age of 18 and able to give consent Control Exclusion Criteria Subjects without a clinical diagnosis of lymphatic filariasis Subjects who are under the age of 18 or unable to give informed consent
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Lymphatic Filariasis<br> | |
| Patients without Lymphatic Filariasis<br> | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dermatology Life Quality Index (DLQI) Domain Scores | The DLQI is a 10-item questionnaire measuring skin-specific quality of life through six domains: Symptoms & Feelings, Daily Activities, Leisure, Work & School, Personal Relationships, and Treatment. Symptoms & Feelings, Daily Activities, Leisure, and Personal Relationships are each scored from 0 to 3, where 0 is associated with no effect on a patient's life, and 3 is associated with a large effect on a patient's life. Work & School and Treatment are each scored from 0 to 3, where 0 is associated with no effect on a patient's life, and 6 is associated with a large effect on a patient's life. | Assessed after enrollment |
| Lymphatic Filariasis-Specific Quality of Life (LFSQQ) Domain Scores | The LFSQQ was developed to assess quality of life in subjects with lymphatic filariasis through seven domains: Mobility, Self-Care, Usual Activities, Disease Burden, Pain/Discomfort, Psychological Health, and Social Participation. Items are scored on a 5-point scale (no problem, mild, moderate, severe, most severe), and scores for each domain are calculated based on the number of questions answered and the raw scores. Scores for each domain range from 0 to 100, where 0 is associated with a worse quality of life and 100 is associated with a better quality of life. | Assessed after enrollment |
| World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) Domain Scores | The WHODAS 2.0 is a generic health and disability assessment tool that describes effects of disease on six domains: Cognition, Mobility, Self-Care, Getting Along, Life Activities, and Participation in Society. Responses are measured on a 5-point scale from 1 (no difficulty) to 5 (extreme difficulty or cannot do). Scores are calculated using a WHO SPSS 36 version syntax for employed subjects and a WHO SPSS 32 version syntax for unemployed subjects. Scores for each domain range from 0 to 100, where 0 is associated with no impairment of health status, and 100 is associated with a greater impairment of health status. | Assessed after enrollment |
|
|||||
NCT05023967
|
Metformin and Nightly Fasting in Women With Early Breast Cancer
|
This phase IIb trial studies the combined effect of prolonged nightly fasting and metformin hydrochloride extended release in decreasing breast tumor cell proliferation and other biomarkers of breast cancer. Preventing invasive breast cancer or DCIS. Metformin is widely used to treat type II diabetes and is associated with a decreased risk of cancer and death in diabetic individuals. Intermittent fasting may protect cancer patients from the toxic effects of chemotherapy agents without causing chronic weight loss. The combination of intermittent fasting and metformin may reduce breast cancer growth and may be used in women at risk for breast cancer or other cancers associated with being overweight.
|
PRIMARY OBJECTIVES:~I. To assess the safety of the experimental intervention based on the frequency of occurrence of a dose limiting toxicity (DLT) in the first 14 participants assigned to the experimental treatment arm.~II. Evaluate the difference in post-treatment Ki67 labeling index (LI) in cancer adjacent ductal carcinoma in situ (DCIS) (in the presence of invasive breast cancer [IBC]), if present, or intraepithelial neoplasia (IEN) (defined as atypical ductal hyperplasia [ADH] or atypical lobular hyperplasia [ALH] or lobular carcinoma in situ [LCIS]) between the active treatment and the control group.~SECONDARY OBJECTIVES:~I. To explore the effect of intervention on the change of expression of PP2A-GSK3beta-MCL-1 axis in pre-post treatment cancer tissue levels.~II. To measure the change in circulating biomarkers: Homeostatic model assessment (HOMA) index, highly sensitive C-reactive protein (CRP) (hsCRP), C-peptide, IGF-I, IGFBP-1, IGFBP-3, free IGF-I, Hb1Ac, lipid profile, adipokines (leptin and adiponectin).~III. To correlate a customized next generation sequencing (NGS) mutational profile panel focused on estrogen receptor (ER) positive (+ve) with the response of Ki67.~IV. To measure the difference of cell death by immunohistochemistry (IHC) for M30 in post- treatment cancer samples between arms.~V. To measure the difference of phosphorylated (p)S6 by IHC in post- treatment cancer samples between arms.~VI. To assess safety and toxicities according to National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 5.0.~VII. To correlate physiological distress, eating habits, tobacco and alcohol consumption with the response of Ki67 between arms.~VIII. To compare the area under the curve (AUC) of glucose levels between arms and within the experimental arm according to different doses of metformin hydrochloride extended release (0 mg, 750 mg and 1500 mg).~OUTLINE: Patients are randomized to 1 of 2 arms.~ARM I: Patients fast for >= 16 hours every night and use the continuous glucose monitoring system for 4-6 weeks. Patients also receive nutritional counseling sessions on days 0 and 10. Beginning week 2, patients also receive metformin hydrochloride extended release orally (PO) once daily (QD) until the day of surgery. Treatment continues for 4-6 weeks (until surgery) in the absence of disease progression or unacceptable toxicity. Patients undergo the collection of blood samples at baseline and at the final study visit (days 28-43), and the collection of tissue at the time of surgery (days 28-43).~ARM II: Patients continue their usual dietary pattern and use the continuous glucose monitoring system for 4-6 weeks (until surgery). Patients undergo the collection of blood samples at baseline and at the final study visit (days 28-43), and the collection of tissue at the time of surgery (days 28-43).~After completion of study intervention, patients are followed up at 30 days.
|
Time Restricted Eating And Metformin (TEAM) in Invasive Breast Cancer (IBC) or Ductal Carcinoma in Situ (DCIS). A Randomized, Phase IIb, Window of Opportunity Presurgical Trial.
|
Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Breast Ductal Carcinoma In Situ, Invasive Breast Carcinoma
|
* Procedure: Biospecimen Collection
* Drug: Extended Release Metformin Hydrochloride
* Other: Monitoring
* Other: Nutritional Assessment
* Other: Short-Term Fasting
|
Inclusion Criteria:~Women with histologically confirmed luminal (ER+ve and/or progesterone [PgR]+ve >= 1%) operable IBC (cT1-2, cN0-1, Mx) candidate to elective surgery and not to neo-adjuvant treatment. Women with larger tumors who refuse neo-adjuvant chemotherapy before surgery can also be eligible. Luminal HER2+ve (cT1, cN0) IBC and DCIS are also eligible~Age >= 18 years~Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)~Leukocytes >= 3,000/microliter~Absolute neutrophil count >= 1,500/microliter~Platelets >= 100,000/microliter~Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 x institutional upper limit of normal~Creatinine within normal institutional limits~Creatinine clearance estimated with Cockcroft-Gault formula > 45 mL/min~Female participants of child-bearing potential must agree to use contraception such as barrier method of birth control or abstinence, prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she has to inform her study physician immediately. The effects of metformin hydrochloride extended release on the developing human fetus at the recommended therapeutic dose are unknown~Ability to understand and the willingness to sign a written informed consent document~Exclusion Criteria:~Body mass index (BMI) < 18.5 Kg/m^2~Previous treatment for breast cancer including chemotherapy and endocrine therapy~Women who are planned to receive neoadjuvant therapy (HER2+ve T2 or N+ve IBC or women < 50 years with luminal B IBC)~Triple negative breast cancer (BC)~Documented history of symptomatic hypoglycemia~Diabetic patients or participants with fasting glucose level >= 126 mg/dL~Known hypersensitivity or intolerance to metformin hydrochloride extended release~Participants should not be receiving any other investigational agents~Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements~History of lactic acidosis~Liver dysfunction including chronic active hepatitis and cirrhosis not compensated~History of vitamin B12 deficiency or megaloblastic anemia~Chronic use of large doses of diuretics (e.g., > 80 mg furosemide)~Current use of oral hormonal contraceptives or female hormones in the last four weeks or 5 half-lives, excluding vaginal creams and intrauterine devices (IUDs)~Concomitant use of topiramate or other carbonic anhydrase inhibitors (e.g., zonisamide, acetazolamide or dichlorphenamide)~Pregnant women are excluded from this study because even though published data from post-marketing studies have not reported a clear association between metformin hydrochloride extended release and major birth defects, miscarriage, or adverse maternal or fetal outcomes when metformin hydrochloride extended release was used during pregnancy, these studies cannot definitely establish the absence of any metformin hydrochloride extended release associated risk because of methodological limitations, including small sample size and inconsistent comparator groups. Because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with metformin hydrochloride extended release, breastfeeding should be discontinued if the mother is treated with metformin hydrochloride extended release. Moreover, prolonged fasting is not recommended in pregnant woman~Women who practice any type of intermittent fasting program~Women who will not have anyone available to assist them in case of need
|
18 Years
| null |
Female
|
No
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of occurrence of dose limiting toxicity | Defined as a hypoglycemic event requiring permanent discontinuation of study treatment or any grade 3 or greater adverse event possibly, probably, or definitely related to the study drug. | Up to 4-6 weeks |
| Change in pre-post treatment Ki67 labeling index in invasive breast cancer (IBC) or ductal carcinoma in situ (DCIS) (in the absence of IBC) | Generalized linear models will be used to assess differences between treatment arms for Ki67. Log transformation will be considered to obtain normal distribution of residuals. Will also evaluate the need to adjust for baseline characteristics and significant confounders (such as body mass index [BMI] and HER2 status). | Baseline up to 4-6 weeks |
| Difference in post-treatment adjacent DCIS (in the presence of IBC), if present, or intraepithelial neoplasia Ki67 between arms | Generalized linear models will be used to assess differences between treatment arms for Ki67. Log transformation will be considered to obtain normal distribution of residuals. Will also evaluate the need to adjust for baseline characteristics and significant confounders (such as BMI and HER2 status). | Post-treatment (4-6 weeks) |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in circulating biomarkers | Will include Homeostatic model assessment index, highly sensitive C-reactive protein, C-peptide, IGF-I, IGFBP-1, IGFBP-3, free IGF-I, Hb1Ac, lipid profile, leptin and adiponectin. Will present full distributions and median values of circulating biomarkers, Ki67, at baseline, after treatment, and of changes and percentage changes (with interquartile ranges) of all continuous variables, by arms. Analysis of covariance (ANCOVA) models will evaluate the associations of post values (after treatment) and changes from baseline by study arms adjusting for baseline values, explanatory variables and possible confounders (such as age and BMI). Normal distribution of residuals from full models will be checked and, if needed, a transformation will be considered. | Baseline up to 4-6 weeks |
| Change of CIP2A-PP2A-GSK3beta-MCL-1 axis in cancer tissue | Will present full distributions and median values of circulating biomarkers, Ki67, at baseline, after treatment, and of changes and percentage changes (with interquartile ranges) of all continuous variables, by arms. ANCOVA models will evaluate the associations of post values (after treatment) and changes from baseline by study arms adjusting for baseline values, explanatory variables and possible confounders (such as age and BMI). Normal distribution of residuals from full models will be checked and, if needed, a transformation will be considered. | Baseline up to 4-6 weeks |
| Change of Ki67 in cancer tissue | Will depend upon next generation sequencing mutational profile obtained in post-treatment surgical specimens. Will present full distributions and median values of circulating biomarkers, Ki67, at baseline, after treatment, and of changes and percentage changes (with interquartile ranges) of all continuous variables, by arms. ANCOVA models will evaluate the associations of post values (after treatment) and changes from baseline by study arms adjusting for baseline values, explanatory variables and possible confounders (such as age and BMI). Normal distribution of residuals from full models will be checked and, if needed, a transformation will be considered. | Baseline up to 4-6 weeks |
| Difference of M30 | Will be assessed between arms. Will be assessed using IHC. | Post-treatment |
| Difference of phosphorylated S6 | Will be assessed between arms. Will be assessed using IHC. | Post-treatment |
| Physiological distress | Will be correlated with response biomarkers. | Up to 4-6 weeks |
| Eating habits | Will be correlated with response biomarkers. | Up to 4-6 weeks |
| Tobacco | Will be correlated with response biomarkers. | Up to 4-6 weeks |
| Alcohol consumption | Will be correlated with response biomarkers. | Up to 4-6 weeks |
| Incidence of adverse events | Evaluated according to the Common Terminology Criteria for Adverse Events version 5.0. | Up to 4-6 weeks |
| Difference of the area under the curve of glucose levels | Will be assessed between arms. | Up to 4-6 weeks |
|
Metformin, Hypoglycemic Agents, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (fasting, glucose monitoring, counseling, metformin)<br>Patients fast for >= 16 hours every night and use the continuous glucose monitoring system for 4-6 weeks. Patients also receive nutritional counseling sessions on days 0 and 10. Beginning week 2, patients also receive metformin hydrochloride extended release PO QD until the day of surgery. Treatment continues for 4-6 weeks (until surgery) in the absence of disease progression or unacceptable toxicity. Patients undergo the collection of blood samples at baseline and at the final study visit (days 28-43), and the collection of tissue at the time of surgery (days 28-43). | Procedure: Biospecimen Collection<br>* Undergo collection of blood and tissue samples<br>* Other names: Specimen Collection;Drug: Extended Release Metformin Hydrochloride<br>* Given PO<br>* Other names: Metformin Hydrochloride Extended Release;Other: Monitoring<br>* Use continuous glucose monitoring system<br>* Other names: monitor;Other: Nutritional Assessment<br>* Receive nutritional counseling<br>* Other names: nutritional counseling;Other: Short-Term Fasting<br>* Perform intermittent fasting<br>* Other names: Short-term Intermittent Fasting;|
| Active Comparator: Arm II (glucose monitoring)<br>Patients continue their usual dietary pattern and use the continuous glucose monitoring system for 4-6 weeks (until surgery). Patients undergo the collection of blood samples at baseline and at the final study visit (days 28-43), and the collection of tissue at the time of surgery (days 28-43). | Procedure: Biospecimen Collection<br>* Undergo collection of blood and tissue samples<br>* Other names: Specimen Collection;Other: Monitoring<br>* Use continuous glucose monitoring system<br>* Other names: monitor;|
|
Metformin and Nightly Fasting in Women With Early Breast Cancer
Study Overview
=================
Brief Summary
-----------------
This phase IIb trial studies the combined effect of prolonged nightly fasting and metformin hydrochloride extended release in decreasing breast tumor cell proliferation and other biomarkers of breast cancer. Preventing invasive breast cancer or DCIS. Metformin is widely used to treat type II diabetes and is associated with a decreased risk of cancer and death in diabetic individuals. Intermittent fasting may protect cancer patients from the toxic effects of chemotherapy agents without causing chronic weight loss. The combination of intermittent fasting and metformin may reduce breast cancer growth and may be used in women at risk for breast cancer or other cancers associated with being overweight.
Detailed Description
-----------------
PRIMARY OBJECTIVES: I. To assess the safety of the experimental intervention based on the frequency of occurrence of a dose limiting toxicity (DLT) in the first 14 participants assigned to the experimental treatment arm. II. Evaluate the difference in post-treatment Ki67 labeling index (LI) in cancer adjacent ductal carcinoma in situ (DCIS) (in the presence of invasive breast cancer [IBC]), if present, or intraepithelial neoplasia (IEN) (defined as atypical ductal hyperplasia [ADH] or atypical lobular hyperplasia [ALH] or lobular carcinoma in situ [LCIS]) between the active treatment and the control group. SECONDARY OBJECTIVES: I. To explore the effect of intervention on the change of expression of PP2A-GSK3beta-MCL-1 axis in pre-post treatment cancer tissue levels. II. To measure the change in circulating biomarkers: Homeostatic model assessment (HOMA) index, highly sensitive C-reactive protein (CRP) (hsCRP), C-peptide, IGF-I, IGFBP-1, IGFBP-3, free IGF-I, Hb1Ac, lipid profile, adipokines (leptin and adiponectin). III. To correlate a customized next generation sequencing (NGS) mutational profile panel focused on estrogen receptor (ER) positive (+ve) with the response of Ki67. IV. To measure the difference of cell death by immunohistochemistry (IHC) for M30 in post- treatment cancer samples between arms. V. To measure the difference of phosphorylated (p)S6 by IHC in post- treatment cancer samples between arms. VI. To assess safety and toxicities according to National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 5.0. VII. To correlate physiological distress, eating habits, tobacco and alcohol consumption with the response of Ki67 between arms. VIII. To compare the area under the curve (AUC) of glucose levels between arms and within the experimental arm according to different doses of metformin hydrochloride extended release (0 mg, 750 mg and 1500 mg). OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients fast for >= 16 hours every night and use the continuous glucose monitoring system for 4-6 weeks. Patients also receive nutritional counseling sessions on days 0 and 10. Beginning week 2, patients also receive metformin hydrochloride extended release orally (PO) once daily (QD) until the day of surgery. Treatment continues for 4-6 weeks (until surgery) in the absence of disease progression or unacceptable toxicity. Patients undergo the collection of blood samples at baseline and at the final study visit (days 28-43), and the collection of tissue at the time of surgery (days 28-43). ARM II: Patients continue their usual dietary pattern and use the continuous glucose monitoring system for 4-6 weeks (until surgery). Patients undergo the collection of blood samples at baseline and at the final study visit (days 28-43), and the collection of tissue at the time of surgery (days 28-43). After completion of study intervention, patients are followed up at 30 days.
Official Title
-----------------
Time Restricted Eating And Metformin (TEAM) in Invasive Breast Cancer (IBC) or Ductal Carcinoma in Situ (DCIS). A Randomized, Phase IIb, Window of Opportunity Presurgical Trial.
Conditions
-----------------
Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Breast Ductal Carcinoma In Situ, Invasive Breast Carcinoma
Intervention / Treatment
-----------------
* Procedure: Biospecimen Collection
* Drug: Extended Release Metformin Hydrochloride
* Other: Monitoring
* Other: Nutritional Assessment
* Other: Short-Term Fasting
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women with histologically confirmed luminal (ER+ve and/or progesterone [PgR]+ve >= 1%) operable IBC (cT1-2, cN0-1, Mx) candidate to elective surgery and not to neo-adjuvant treatment. Women with larger tumors who refuse neo-adjuvant chemotherapy before surgery can also be eligible. Luminal HER2+ve (cT1, cN0) IBC and DCIS are also eligible Age >= 18 years Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%) Leukocytes >= 3,000/microliter Absolute neutrophil count >= 1,500/microliter Platelets >= 100,000/microliter Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 x institutional upper limit of normal Creatinine within normal institutional limits Creatinine clearance estimated with Cockcroft-Gault formula > 45 mL/min Female participants of child-bearing potential must agree to use contraception such as barrier method of birth control or abstinence, prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she has to inform her study physician immediately. The effects of metformin hydrochloride extended release on the developing human fetus at the recommended therapeutic dose are unknown Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Body mass index (BMI) < 18.5 Kg/m^2 Previous treatment for breast cancer including chemotherapy and endocrine therapy Women who are planned to receive neoadjuvant therapy (HER2+ve T2 or N+ve IBC or women < 50 years with luminal B IBC) Triple negative breast cancer (BC) Documented history of symptomatic hypoglycemia Diabetic patients or participants with fasting glucose level >= 126 mg/dL Known hypersensitivity or intolerance to metformin hydrochloride extended release Participants should not be receiving any other investigational agents Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements History of lactic acidosis Liver dysfunction including chronic active hepatitis and cirrhosis not compensated History of vitamin B12 deficiency or megaloblastic anemia Chronic use of large doses of diuretics (e.g., > 80 mg furosemide) Current use of oral hormonal contraceptives or female hormones in the last four weeks or 5 half-lives, excluding vaginal creams and intrauterine devices (IUDs) Concomitant use of topiramate or other carbonic anhydrase inhibitors (e.g., zonisamide, acetazolamide or dichlorphenamide) Pregnant women are excluded from this study because even though published data from post-marketing studies have not reported a clear association between metformin hydrochloride extended release and major birth defects, miscarriage, or adverse maternal or fetal outcomes when metformin hydrochloride extended release was used during pregnancy, these studies cannot definitely establish the absence of any metformin hydrochloride extended release associated risk because of methodological limitations, including small sample size and inconsistent comparator groups. Because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with metformin hydrochloride extended release, breastfeeding should be discontinued if the mother is treated with metformin hydrochloride extended release. Moreover, prolonged fasting is not recommended in pregnant woman Women who practice any type of intermittent fasting program Women who will not have anyone available to assist them in case of need
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
Female
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (fasting, glucose monitoring, counseling, metformin)<br>Patients fast for >= 16 hours every night and use the continuous glucose monitoring system for 4-6 weeks. Patients also receive nutritional counseling sessions on days 0 and 10. Beginning week 2, patients also receive metformin hydrochloride extended release PO QD until the day of surgery. Treatment continues for 4-6 weeks (until surgery) in the absence of disease progression or unacceptable toxicity. Patients undergo the collection of blood samples at baseline and at the final study visit (days 28-43), and the collection of tissue at the time of surgery (days 28-43). | Procedure: Biospecimen Collection<br>* Undergo collection of blood and tissue samples<br>* Other names: Specimen Collection;Drug: Extended Release Metformin Hydrochloride<br>* Given PO<br>* Other names: Metformin Hydrochloride Extended Release;Other: Monitoring<br>* Use continuous glucose monitoring system<br>* Other names: monitor;Other: Nutritional Assessment<br>* Receive nutritional counseling<br>* Other names: nutritional counseling;Other: Short-Term Fasting<br>* Perform intermittent fasting<br>* Other names: Short-term Intermittent Fasting;|
| Active Comparator: Arm II (glucose monitoring)<br>Patients continue their usual dietary pattern and use the continuous glucose monitoring system for 4-6 weeks (until surgery). Patients undergo the collection of blood samples at baseline and at the final study visit (days 28-43), and the collection of tissue at the time of surgery (days 28-43). | Procedure: Biospecimen Collection<br>* Undergo collection of blood and tissue samples<br>* Other names: Specimen Collection;Other: Monitoring<br>* Use continuous glucose monitoring system<br>* Other names: monitor;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of occurrence of dose limiting toxicity | Defined as a hypoglycemic event requiring permanent discontinuation of study treatment or any grade 3 or greater adverse event possibly, probably, or definitely related to the study drug. | Up to 4-6 weeks |
| Change in pre-post treatment Ki67 labeling index in invasive breast cancer (IBC) or ductal carcinoma in situ (DCIS) (in the absence of IBC) | Generalized linear models will be used to assess differences between treatment arms for Ki67. Log transformation will be considered to obtain normal distribution of residuals. Will also evaluate the need to adjust for baseline characteristics and significant confounders (such as body mass index [BMI] and HER2 status). | Baseline up to 4-6 weeks |
| Difference in post-treatment adjacent DCIS (in the presence of IBC), if present, or intraepithelial neoplasia Ki67 between arms | Generalized linear models will be used to assess differences between treatment arms for Ki67. Log transformation will be considered to obtain normal distribution of residuals. Will also evaluate the need to adjust for baseline characteristics and significant confounders (such as BMI and HER2 status). | Post-treatment (4-6 weeks) |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in circulating biomarkers | Will include Homeostatic model assessment index, highly sensitive C-reactive protein, C-peptide, IGF-I, IGFBP-1, IGFBP-3, free IGF-I, Hb1Ac, lipid profile, leptin and adiponectin. Will present full distributions and median values of circulating biomarkers, Ki67, at baseline, after treatment, and of changes and percentage changes (with interquartile ranges) of all continuous variables, by arms. Analysis of covariance (ANCOVA) models will evaluate the associations of post values (after treatment) and changes from baseline by study arms adjusting for baseline values, explanatory variables and possible confounders (such as age and BMI). Normal distribution of residuals from full models will be checked and, if needed, a transformation will be considered. | Baseline up to 4-6 weeks |
| Change of CIP2A-PP2A-GSK3beta-MCL-1 axis in cancer tissue | Will present full distributions and median values of circulating biomarkers, Ki67, at baseline, after treatment, and of changes and percentage changes (with interquartile ranges) of all continuous variables, by arms. ANCOVA models will evaluate the associations of post values (after treatment) and changes from baseline by study arms adjusting for baseline values, explanatory variables and possible confounders (such as age and BMI). Normal distribution of residuals from full models will be checked and, if needed, a transformation will be considered. | Baseline up to 4-6 weeks |
| Change of Ki67 in cancer tissue | Will depend upon next generation sequencing mutational profile obtained in post-treatment surgical specimens. Will present full distributions and median values of circulating biomarkers, Ki67, at baseline, after treatment, and of changes and percentage changes (with interquartile ranges) of all continuous variables, by arms. ANCOVA models will evaluate the associations of post values (after treatment) and changes from baseline by study arms adjusting for baseline values, explanatory variables and possible confounders (such as age and BMI). Normal distribution of residuals from full models will be checked and, if needed, a transformation will be considered. | Baseline up to 4-6 weeks |
| Difference of M30 | Will be assessed between arms. Will be assessed using IHC. | Post-treatment |
| Difference of phosphorylated S6 | Will be assessed between arms. Will be assessed using IHC. | Post-treatment |
| Physiological distress | Will be correlated with response biomarkers. | Up to 4-6 weeks |
| Eating habits | Will be correlated with response biomarkers. | Up to 4-6 weeks |
| Tobacco | Will be correlated with response biomarkers. | Up to 4-6 weeks |
| Alcohol consumption | Will be correlated with response biomarkers. | Up to 4-6 weeks |
| Incidence of adverse events | Evaluated according to the Common Terminology Criteria for Adverse Events version 5.0. | Up to 4-6 weeks |
| Difference of the area under the curve of glucose levels | Will be assessed between arms. | Up to 4-6 weeks |
|
|
NCT01964092
|
Effect Evaluation of Individual Placement and Support (IPS)
|
Roughly one third of disability pensions issued in Norway are classified as mental and behavioral disorders. The proposed study aims to evaluate the effect of an innovative intervention for returning people with moderate to severe mental health disorders to work: Individual Placement and Support (IPS).
|
The current employment schemes offered to this diagnostic group are primarily based on a train-and-place principle with assisted or sheltered employment. Building on a place-and-train principle, rather, the IPS model of supported employment in real-life competitive work settings has proven largely successful in previous studies, but has never been tested in this group in the Norwegian context.
|
Effect Evaluation of Individual Placement and Support (IPS)
|
Anxiety, Psychosis, Substance Abuse, Depression
|
* Behavioral: Individual Placement and Support
* Behavioral: Ordinary employment schemes
|
Inclusion Criteria:~Participants must be undergoing treatment for moderate to severe mental health problems.~Participants must have an expressed desire to work.~Participants must have sufficient Norwegian reading and writing skills.~Exclusion Criteria:~Participants are not undergoing treatment for moderate to severe mental health problems.~Participants do not have an expressed desire to work.~Participants do not have sufficient Norwegian reading and writing skills.
|
18 Years
|
67 Years
|
All
|
No
|
Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Labor Market Participation in Ordinary Paid Employment, or Education. | Labor market participation is operationalized as being registered in the Norwegian Labour and Welfare Administrations (NAV) State Register of Employers and Employees, and not as a recipient of unemployment or sickness benefits, not receiving work assessment allowance or disability pension with a higher degree of disability than by study inclusion, and registered yearly income. | 1 year (2016) |
|
Disability, Individual placement and support, Mental health, Quality of life, Randomized controlled trial, Rehabilitation, Return to work, Supported employment
|
Substance-Related Disorders, Mental Disorders, Chemically-Induced Disorders
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Individual Placement and Support<br>Individual Placement and Support (IPS) is a well-defined intervention aiming to help people with disabilities participate in the competitive labor market by working in jobs they prefer with the professional help that they need. IPS actively facilitates job acquisition and provides ongoing support once the client is employed. | Behavioral: Individual Placement and Support<br> <br> |
| Active Comparator: Ordinary employment schemes<br>The control group will receive treatment as usual in terms of the ordinary employment schemes offered to this group, primarily Work with assistance and/or Traineeship in a sheltered business. | Behavioral: Ordinary employment schemes<br> <br> |
|
Effect Evaluation of Individual Placement and Support (IPS)
Study Overview
=================
Brief Summary
-----------------
Roughly one third of disability pensions issued in Norway are classified as mental and behavioral disorders. The proposed study aims to evaluate the effect of an innovative intervention for returning people with moderate to severe mental health disorders to work: Individual Placement and Support (IPS).
Detailed Description
-----------------
The current employment schemes offered to this diagnostic group are primarily based on a train-and-place principle with assisted or sheltered employment. Building on a place-and-train principle, rather, the IPS model of supported employment in real-life competitive work settings has proven largely successful in previous studies, but has never been tested in this group in the Norwegian context.
Official Title
-----------------
Effect Evaluation of Individual Placement and Support (IPS)
Conditions
-----------------
Anxiety, Psychosis, Substance Abuse, Depression
Intervention / Treatment
-----------------
* Behavioral: Individual Placement and Support
* Behavioral: Ordinary employment schemes
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants must be undergoing treatment for moderate to severe mental health problems. Participants must have an expressed desire to work. Participants must have sufficient Norwegian reading and writing skills. Exclusion Criteria: Participants are not undergoing treatment for moderate to severe mental health problems. Participants do not have an expressed desire to work. Participants do not have sufficient Norwegian reading and writing skills.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 67 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Individual Placement and Support<br>Individual Placement and Support (IPS) is a well-defined intervention aiming to help people with disabilities participate in the competitive labor market by working in jobs they prefer with the professional help that they need. IPS actively facilitates job acquisition and provides ongoing support once the client is employed. | Behavioral: Individual Placement and Support<br> <br> |
| Active Comparator: Ordinary employment schemes<br>The control group will receive treatment as usual in terms of the ordinary employment schemes offered to this group, primarily Work with assistance and/or Traineeship in a sheltered business. | Behavioral: Ordinary employment schemes<br> <br> |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Labor Market Participation in Ordinary Paid Employment, or Education. | Labor market participation is operationalized as being registered in the Norwegian Labour and Welfare Administrations (NAV) State Register of Employers and Employees, and not as a recipient of unemployment or sickness benefits, not receiving work assessment allowance or disability pension with a higher degree of disability than by study inclusion, and registered yearly income. | 1 year (2016) |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Disability, Individual placement and support, Mental health, Quality of life, Randomized controlled trial, Rehabilitation, Return to work, Supported employment
|
|
NCT00874731
|
A Study to Evaluate the Effect of MK-8669 (Ridaforolimus) on QTc Interval in Participants With Advanced Cancer (MK-8669-037)
|
To assess the potential for ridaforolimus to prolong the QTc interval (an effect on the electrical activity of the heart) in participants with advanced cancer. This study will be done in 2 parts. Part 1 (Pt 1) will evaluate the effect of a single 100 mg dose of ridaforolimus on QT interval in participants with advanced cancer. Fridericias's correction (QTcF) will be used. In Part 2 (Pt 2), participants will receive ridaforolimus at the current therapeutic dose (40 mg x 5 days).
|
A Clinical Trial to Assess the Effect of Ridaforolimus (AP23573; MK-8669) on QTc Interval in Patients
|
Metastatic or Locally Advanced Cancer
|
* Drug: Ridaforolimus 100 mg
* Drug: Ridaforolimus 40 mg
* Drug: Placebo
|
Inclusion Criteria:~Participant must have metastatic or locally advanced cancer which has failed to respond to standard therapy or no therapy exists.~If the participant is a female, she must be postmenopausal or if she is of childbearing potential she must have blood pregnancy tests during the study and be willing to use 2 methods of contraception.~If the participant is male and has female partners of child-bearing potential, he must agree to use a medically acceptable method of contraception during the study and for 30 days after the last dose of study drug.~Exclusion Criteria:~Participant has had chemotherapy, radiotherapy or biological therapy within the past 4 weeks.~Participant is currently receiving other anti-cancer therapy.~Participant is currently participating or has participated in a study with an investigation drug or device within the last 30 days.~Participant has a primary central nervous system tumor or active brain metastases.~Participant has a psychiatric disorder.~Participant uses illegal drugs.~Participant is pregnant or breastfeeding.~Participant is known to be human immunodeficiency virus (HIV) positive.~Participant has a known history of Hepatitis B or C.~Participant has newly diagnosed diabetes.~Participant has an active infection.~Participant is unable to swallow capsules.~Participant has received a blood transfusion with one week of study entry.~Participant has a history of cardiac problems including heart failure, myocardial infarction, unstable angina, congestive heart failure or cardiac arrhythmia.~Participant has a known sensitivity to the components of the study drug.~Participant has not adequately recovered from any prior surgical procedure.~Participant does not agree to refrain from use of herbal remedies and consumption of grapefruit juice for 2 weeks prior to and during the study.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 0.5 Hours | The mean change from baseline (CFB) in QTcF at 0.5 hours post-dose was assessed. At baseline (pre-dose) and at 0.5 hours post-dose, 5 replicate electrocardiograms (ECGs) were collected to reduce measurement variability. The 5 replicate QTcF values were averaged to calculate the QTcF value for each participant. Further, each participant served as their own control for the calculation of CFB in QTcF after placebo and ridaforolimus 100 mg dosing. Additionally, CFB in QTcF after single ridaforolimus 100 mg dosing for each participant was adjusted for the CFB in QTcF observed after placebo dosing. | Baseline and 0.5 hours post-dose on Days 1 & 2 of Part 1 |
| Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 1 Hour | The mean change from baseline (CFB) in QTcF at 1 hour post-dose was assessed. At baseline (pre-dose) and at 1 hour post-dose, 5 replicate electrocardiograms (ECGs) were collected to reduce measurement variability. The 5 replicate QTcF values were averaged to calculate the QTcF value for each participant. Further, each participant served as their own control for the calculation of CFB in QTcF after placebo and ridaforolimus 100 mg dosing. Additionally, CFB in QTcF after single ridaforolimus 100 mg dosing for each participant was adjusted for the CFB in QTcF observed after placebo dosing. | Baseline and 1 hour post-dose on Days 1 & 2 of Part 1 |
| Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 2 Hours | The mean change from baseline (CFB) in QTcF at 2 hours post-dose was assessed. At baseline (pre-dose) and at 2 hours post-dose, 5 replicate electrocardiograms (ECGs) were collected to reduce measurement variability. The 5 replicate QTcF values were averaged to calculate the QTcF value for each participant. Further, each participant served as their own control for the calculation of CFB in QTcF after placebo and ridaforolimus 100 mg dosing. Additionally, CFB in QTcF after single ridaforolimus 100 mg dosing for each participant was adjusted for the CFB in QTcF observed after placebo dosing. | Baseline and 2 hours post-dose on Days 1 & 2 of Part 1 |
| Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 3 Hours | The mean change from baseline (CFB) in QTcF at 3 hours post-dose was assessed. At baseline (pre-dose) and at 3 hours post-dose, 5 replicate electrocardiograms (ECGs) were collected to reduce measurement variability. The 5 replicate QTcF values were averaged to calculate the QTcF value for each participant. Further, each participant served as their own control for the calculation of CFB in QTcF after placebo and ridaforolimus 100 mg dosing. Additionally, CFB in QTcF after single ridaforolimus 100 mg dosing for each participant was adjusted for the CFB in QTcF observed after placebo dosing. | Baseline and 3 hours post-dose on Days 1 & 2 of Part 1 |
| Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 4 Hours | The mean change from baseline (CFB) in QTcF at 4 hours post-dose was assessed. At baseline (pre-dose) and at 4 hours post-dose, 5 replicate electrocardiograms (ECGs) were collected to reduce measurement variability. The 5 replicate QTcF values were averaged to calculate the QTcF value for each participant. Further, each participant served as their own control for the calculation of CFB in QTcF after placebo and ridaforolimus 100 mg dosing. Additionally, CFB in QTcF after single ridaforolimus 100 mg dosing for each participant was adjusted for the CFB in QTcF observed after placebo dosing. | Baseline and 4 hours post-dose on Days 1 & 2 of Part 1 |
| Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 6 Hours | The mean change from baseline (CFB) in QTcF at 6 hours post-dose was assessed. At baseline (pre-dose) and at 6 hours post-dose, 5 replicate electrocardiograms (ECGs) were collected to reduce measurement variability. The 5 replicate QTcF values were averaged to calculate the QTcF value for each participant. Further, each participant served as their own control for the calculation of CFB in QTcF after placebo and ridaforolimus 100 mg dosing. Additionally, CFB in QTcF after single ridaforolimus 100 mg dosing for each participant was adjusted for the CFB in QTcF observed after placebo dosing. | Baseline and 6 hours post-dose on Days 1 & 2 of Part 1 |
| Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 8 Hours | The mean change from baseline (CFB) in QTcF at 8 hours post-dose was assessed. At baseline (pre-dose) and at 8 hours post-dose, 5 replicate electrocardiograms (ECGs) were collected to reduce measurement variability. The 5 replicate QTcF values were averaged to calculate the QTcF value for each participant. Further, each participant served as their own control for the calculation of CFB in QTcF after placebo and ridaforolimus 100 mg dosing. Additionally, CFB in QTcF after single ridaforolimus 100 mg dosing for each participant was adjusted for the CFB in QTcF observed after placebo dosing. | Baseline and 8 hours post-dose on Days 1 & 2 of Part 1 |
| Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 10 Hours | The mean change from baseline (CFB) in QTcF at 10 hours post-dose was assessed. At baseline (pre-dose) and at 10 hours post-dose, 5 replicate electrocardiograms (ECGs) were collected to reduce measurement variability. The 5 replicate QTcF values were averaged to calculate the QTcF value for each participant. Further, each participant served as their own control for the calculation of CFB in QTcF after placebo and ridaforolimus 100 mg dosing. Additionally, CFB in QTcF after single ridaforolimus 100 mg dosing for each participant was adjusted for the CFB in QTcF observed after placebo dosing. | Baseline and 10 hours post-dose on Days 1 & 2 of Part 1 |
| Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 24 Hours | The mean change from baseline (CFB) in QTcF at 24 hours post-dose was assessed. At baseline (pre-dose) and at 24 hours post-dose, 5 replicate electrocardiograms (ECGs) were collected to reduce measurement variability. The 5 replicate QTcF values were averaged to calculate the QTcF value for each participant. Further, each participant served as their own control for the calculation of CFB in QTcF after placebo and ridaforolimus 100 mg dosing. Additionally, CFB in QTcF after single ridaforolimus 100 mg dosing for each participant was adjusted for the CFB in QTcF observed after placebo dosing. | Baseline and 24 hours post-dose on Days 1 & 2 of Part 1 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing an Adverse Event (AE) | The number of participants experiencing an AE was assessed. An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. Participants experiencing AEs were counted under the treatment they received when the AE occurred. Participants experiencing AEs during the washout period between Part 1 and Part 2 are counted in the Pt 1, Day 2. Ridaforolimus 100 mg arm. | Up to 7 months |
| Number of Participants Discontinuing Study Treatment Due to an Adverse Event | The number of participants discontinuing study treatment due to an AE was assessed. An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. Participants discontinuing study treatment due to an AE were counted as discontinuing under the treatment they received when the AE occurred. | Up to 6 months |
|
Sirolimus, Anti-Bacterial Agents, Anti-Infective Agents, Antibiotics, Antineoplastic, Antineoplastic Agents, Antifungal Agents, Immunosuppressive Agents, Immunologic Factors, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pt 1. Placebo/Ridaforolimus 100 mg; Pt 2. Ridaforolimus 40 mg<br>[Pt 1, Day 1]: Participants received a single dose of placebo (10 oral tablets) on Day 1 of Part 1. [Pt 1, Day 2]: Following completion of Part 1 / Day 1, participants received a single dose of ridaforolimus 100 mg (10 x 10 mg oral tablets) on Day 2 of Part 1. Following completion of Part 1 / Day 2, participants entered a washout period of ≥5 days before the first dose Part 2. [Pt 2]: Following completion of Part 1, participants received ridaforolimus 40 mg (4 x 10 mg oral tablets) given once daily (QD) for 5 consecutive days followed by 2 days off-drug. | Drug: Ridaforolimus 100 mg<br>* Part 1: A single oral dose of 100 mg ridaforolimus (10 x 10 mg tablets) was given on Day 2.<br>* Other names: deforolimus (until May 2009);Drug: Ridaforolimus 40 mg<br>* Part 2 (optional): Ridaforolimus 40 mg (4 x 10 mg tablets) was received on a regimen of daily oral doses for 5 consecutive days followed by 2 days off-drug.<br>* Other names: deforolimus (until May 2009);Drug: Placebo<br>* Part 1: A single oral dose of placebo (10 x placebo tablets) was given on Day 1.<br>|
|
A Study to Evaluate the Effect of MK-8669 (Ridaforolimus) on QTc Interval in Participants With Advanced Cancer (MK-8669-037)
Study Overview
=================
Brief Summary
-----------------
To assess the potential for ridaforolimus to prolong the QTc interval (an effect on the electrical activity of the heart) in participants with advanced cancer. This study will be done in 2 parts. Part 1 (Pt 1) will evaluate the effect of a single 100 mg dose of ridaforolimus on QT interval in participants with advanced cancer. Fridericias's correction (QTcF) will be used. In Part 2 (Pt 2), participants will receive ridaforolimus at the current therapeutic dose (40 mg x 5 days).
Official Title
-----------------
A Clinical Trial to Assess the Effect of Ridaforolimus (AP23573; MK-8669) on QTc Interval in Patients
Conditions
-----------------
Metastatic or Locally Advanced Cancer
Intervention / Treatment
-----------------
* Drug: Ridaforolimus 100 mg
* Drug: Ridaforolimus 40 mg
* Drug: Placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participant must have metastatic or locally advanced cancer which has failed to respond to standard therapy or no therapy exists. If the participant is a female, she must be postmenopausal or if she is of childbearing potential she must have blood pregnancy tests during the study and be willing to use 2 methods of contraception. If the participant is male and has female partners of child-bearing potential, he must agree to use a medically acceptable method of contraception during the study and for 30 days after the last dose of study drug. Exclusion Criteria: Participant has had chemotherapy, radiotherapy or biological therapy within the past 4 weeks. Participant is currently receiving other anti-cancer therapy. Participant is currently participating or has participated in a study with an investigation drug or device within the last 30 days. Participant has a primary central nervous system tumor or active brain metastases. Participant has a psychiatric disorder. Participant uses illegal drugs. Participant is pregnant or breastfeeding. Participant is known to be human immunodeficiency virus (HIV) positive. Participant has a known history of Hepatitis B or C. Participant has newly diagnosed diabetes. Participant has an active infection. Participant is unable to swallow capsules. Participant has received a blood transfusion with one week of study entry. Participant has a history of cardiac problems including heart failure, myocardial infarction, unstable angina, congestive heart failure or cardiac arrhythmia. Participant has a known sensitivity to the components of the study drug. Participant has not adequately recovered from any prior surgical procedure. Participant does not agree to refrain from use of herbal remedies and consumption of grapefruit juice for 2 weeks prior to and during the study.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pt 1. Placebo/Ridaforolimus 100 mg; Pt 2. Ridaforolimus 40 mg<br>[Pt 1, Day 1]: Participants received a single dose of placebo (10 oral tablets) on Day 1 of Part 1. [Pt 1, Day 2]: Following completion of Part 1 / Day 1, participants received a single dose of ridaforolimus 100 mg (10 x 10 mg oral tablets) on Day 2 of Part 1. Following completion of Part 1 / Day 2, participants entered a washout period of ≥5 days before the first dose Part 2. [Pt 2]: Following completion of Part 1, participants received ridaforolimus 40 mg (4 x 10 mg oral tablets) given once daily (QD) for 5 consecutive days followed by 2 days off-drug. | Drug: Ridaforolimus 100 mg<br>* Part 1: A single oral dose of 100 mg ridaforolimus (10 x 10 mg tablets) was given on Day 2.<br>* Other names: deforolimus (until May 2009);Drug: Ridaforolimus 40 mg<br>* Part 2 (optional): Ridaforolimus 40 mg (4 x 10 mg tablets) was received on a regimen of daily oral doses for 5 consecutive days followed by 2 days off-drug.<br>* Other names: deforolimus (until May 2009);Drug: Placebo<br>* Part 1: A single oral dose of placebo (10 x placebo tablets) was given on Day 1.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 0.5 Hours | The mean change from baseline (CFB) in QTcF at 0.5 hours post-dose was assessed. At baseline (pre-dose) and at 0.5 hours post-dose, 5 replicate electrocardiograms (ECGs) were collected to reduce measurement variability. The 5 replicate QTcF values were averaged to calculate the QTcF value for each participant. Further, each participant served as their own control for the calculation of CFB in QTcF after placebo and ridaforolimus 100 mg dosing. Additionally, CFB in QTcF after single ridaforolimus 100 mg dosing for each participant was adjusted for the CFB in QTcF observed after placebo dosing. | Baseline and 0.5 hours post-dose on Days 1 & 2 of Part 1 |
| Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 1 Hour | The mean change from baseline (CFB) in QTcF at 1 hour post-dose was assessed. At baseline (pre-dose) and at 1 hour post-dose, 5 replicate electrocardiograms (ECGs) were collected to reduce measurement variability. The 5 replicate QTcF values were averaged to calculate the QTcF value for each participant. Further, each participant served as their own control for the calculation of CFB in QTcF after placebo and ridaforolimus 100 mg dosing. Additionally, CFB in QTcF after single ridaforolimus 100 mg dosing for each participant was adjusted for the CFB in QTcF observed after placebo dosing. | Baseline and 1 hour post-dose on Days 1 & 2 of Part 1 |
| Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 2 Hours | The mean change from baseline (CFB) in QTcF at 2 hours post-dose was assessed. At baseline (pre-dose) and at 2 hours post-dose, 5 replicate electrocardiograms (ECGs) were collected to reduce measurement variability. The 5 replicate QTcF values were averaged to calculate the QTcF value for each participant. Further, each participant served as their own control for the calculation of CFB in QTcF after placebo and ridaforolimus 100 mg dosing. Additionally, CFB in QTcF after single ridaforolimus 100 mg dosing for each participant was adjusted for the CFB in QTcF observed after placebo dosing. | Baseline and 2 hours post-dose on Days 1 & 2 of Part 1 |
| Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 3 Hours | The mean change from baseline (CFB) in QTcF at 3 hours post-dose was assessed. At baseline (pre-dose) and at 3 hours post-dose, 5 replicate electrocardiograms (ECGs) were collected to reduce measurement variability. The 5 replicate QTcF values were averaged to calculate the QTcF value for each participant. Further, each participant served as their own control for the calculation of CFB in QTcF after placebo and ridaforolimus 100 mg dosing. Additionally, CFB in QTcF after single ridaforolimus 100 mg dosing for each participant was adjusted for the CFB in QTcF observed after placebo dosing. | Baseline and 3 hours post-dose on Days 1 & 2 of Part 1 |
| Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 4 Hours | The mean change from baseline (CFB) in QTcF at 4 hours post-dose was assessed. At baseline (pre-dose) and at 4 hours post-dose, 5 replicate electrocardiograms (ECGs) were collected to reduce measurement variability. The 5 replicate QTcF values were averaged to calculate the QTcF value for each participant. Further, each participant served as their own control for the calculation of CFB in QTcF after placebo and ridaforolimus 100 mg dosing. Additionally, CFB in QTcF after single ridaforolimus 100 mg dosing for each participant was adjusted for the CFB in QTcF observed after placebo dosing. | Baseline and 4 hours post-dose on Days 1 & 2 of Part 1 |
| Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 6 Hours | The mean change from baseline (CFB) in QTcF at 6 hours post-dose was assessed. At baseline (pre-dose) and at 6 hours post-dose, 5 replicate electrocardiograms (ECGs) were collected to reduce measurement variability. The 5 replicate QTcF values were averaged to calculate the QTcF value for each participant. Further, each participant served as their own control for the calculation of CFB in QTcF after placebo and ridaforolimus 100 mg dosing. Additionally, CFB in QTcF after single ridaforolimus 100 mg dosing for each participant was adjusted for the CFB in QTcF observed after placebo dosing. | Baseline and 6 hours post-dose on Days 1 & 2 of Part 1 |
| Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 8 Hours | The mean change from baseline (CFB) in QTcF at 8 hours post-dose was assessed. At baseline (pre-dose) and at 8 hours post-dose, 5 replicate electrocardiograms (ECGs) were collected to reduce measurement variability. The 5 replicate QTcF values were averaged to calculate the QTcF value for each participant. Further, each participant served as their own control for the calculation of CFB in QTcF after placebo and ridaforolimus 100 mg dosing. Additionally, CFB in QTcF after single ridaforolimus 100 mg dosing for each participant was adjusted for the CFB in QTcF observed after placebo dosing. | Baseline and 8 hours post-dose on Days 1 & 2 of Part 1 |
| Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 10 Hours | The mean change from baseline (CFB) in QTcF at 10 hours post-dose was assessed. At baseline (pre-dose) and at 10 hours post-dose, 5 replicate electrocardiograms (ECGs) were collected to reduce measurement variability. The 5 replicate QTcF values were averaged to calculate the QTcF value for each participant. Further, each participant served as their own control for the calculation of CFB in QTcF after placebo and ridaforolimus 100 mg dosing. Additionally, CFB in QTcF after single ridaforolimus 100 mg dosing for each participant was adjusted for the CFB in QTcF observed after placebo dosing. | Baseline and 10 hours post-dose on Days 1 & 2 of Part 1 |
| Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 24 Hours | The mean change from baseline (CFB) in QTcF at 24 hours post-dose was assessed. At baseline (pre-dose) and at 24 hours post-dose, 5 replicate electrocardiograms (ECGs) were collected to reduce measurement variability. The 5 replicate QTcF values were averaged to calculate the QTcF value for each participant. Further, each participant served as their own control for the calculation of CFB in QTcF after placebo and ridaforolimus 100 mg dosing. Additionally, CFB in QTcF after single ridaforolimus 100 mg dosing for each participant was adjusted for the CFB in QTcF observed after placebo dosing. | Baseline and 24 hours post-dose on Days 1 & 2 of Part 1 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing an Adverse Event (AE) | The number of participants experiencing an AE was assessed. An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. Participants experiencing AEs were counted under the treatment they received when the AE occurred. Participants experiencing AEs during the washout period between Part 1 and Part 2 are counted in the Pt 1, Day 2. Ridaforolimus 100 mg arm. | Up to 7 months |
| Number of Participants Discontinuing Study Treatment Due to an Adverse Event | The number of participants discontinuing study treatment due to an AE was assessed. An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. Participants discontinuing study treatment due to an AE were counted as discontinuing under the treatment they received when the AE occurred. | Up to 6 months |
|
||
NCT03883737
|
Percutaneous Neuromodulation on the Anterior Pain Knee
|
Anterior knee pain (AKP) is one of the most frequent pathologies of the lower limb, in young and adult subjects. In the field of Physiotherapy, ultrasound-guided Percutaneous Neuromodulation (PNM) is defined as the application through a needle with ultrasound guidance of an electrical current at low or medium frequency, seeking a sensitive and / or motor response of a peripheral nerve in some point of its trajectory, or of a muscle in a motor point, with a therapeutic objective. The objective of this study is to analyze that the effect of PNM on the femoral nerve produces statistically significant changes in pain, joint range and knee functionality in patients with chronic AKP. Thirty subjects will be recruited, which will be divided into 2 groups: group 1 to which PNM will be applied to the femoral nerve of the pain knee; and group 2 to which PNM will be applied to the femoral nerve of the non-pain knee. The PNM intervention with NMP will consist in the single application of an asymmetric rectangular biphasic current (250 microseconds, 10 Hz)
|
Effect of the Ultrasound-guided Percutaneous Neuromodulation on the Anterior Pain Knee: a Pilot Study
|
Neuromodulation, Anterior Pain Knee, Femoral Nerve
|
* Other: PNM
|
Inclusion Criteria:~chronic anterior knee pain >3 months~older than 18 years-old~Exclusion Criteria:~Surgical intervention in the intervention area~Prosthesis or osteosynthesis in the intervention area~Cardiac or tumoral diseases~Coagulopathies~Be under the effects of certain medications~contraindication characteristic of the puncture
|
18 Years
|
50 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| visual analog scale (VAS) (0, no pain; 100, maximum pain). | pain | up to 1 week |
| range joint | goniometer | up to 1 week |
| VISA-p questionnaire (0, maximum pain; 100, no pain). | Functional pain | up to 1 week |
| Kujala questionnaire (0, maximum pain; 100, no pain). | Functional pain | up to 1 week |
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: PNM in pain knee<br>participants in whom PNM will be applied to the femoral nerve of the pain knee | Other: PNM<br>* an asymmetric rectangular biphasic current (250 microseconds, 10 Hz)<br>|
| Experimental: Group 2: PNM in non-pain knee<br>participants in whom PNM will be applied to the femoral nerve of the non-pain knee | Other: PNM<br>* an asymmetric rectangular biphasic current (250 microseconds, 10 Hz)<br>|
|
Percutaneous Neuromodulation on the Anterior Pain Knee
Study Overview
=================
Brief Summary
-----------------
Anterior knee pain (AKP) is one of the most frequent pathologies of the lower limb, in young and adult subjects. In the field of Physiotherapy, ultrasound-guided Percutaneous Neuromodulation (PNM) is defined as the application through a needle with ultrasound guidance of an electrical current at low or medium frequency, seeking a sensitive and / or motor response of a peripheral nerve in some point of its trajectory, or of a muscle in a motor point, with a therapeutic objective. The objective of this study is to analyze that the effect of PNM on the femoral nerve produces statistically significant changes in pain, joint range and knee functionality in patients with chronic AKP. Thirty subjects will be recruited, which will be divided into 2 groups: group 1 to which PNM will be applied to the femoral nerve of the pain knee; and group 2 to which PNM will be applied to the femoral nerve of the non-pain knee. The PNM intervention with NMP will consist in the single application of an asymmetric rectangular biphasic current (250 microseconds, 10 Hz)
Official Title
-----------------
Effect of the Ultrasound-guided Percutaneous Neuromodulation on the Anterior Pain Knee: a Pilot Study
Conditions
-----------------
Neuromodulation, Anterior Pain Knee, Femoral Nerve
Intervention / Treatment
-----------------
* Other: PNM
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: chronic anterior knee pain >3 months older than 18 years-old Exclusion Criteria: Surgical intervention in the intervention area Prosthesis or osteosynthesis in the intervention area Cardiac or tumoral diseases Coagulopathies Be under the effects of certain medications contraindication characteristic of the puncture
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: PNM in pain knee<br>participants in whom PNM will be applied to the femoral nerve of the pain knee | Other: PNM<br>* an asymmetric rectangular biphasic current (250 microseconds, 10 Hz)<br>|
| Experimental: Group 2: PNM in non-pain knee<br>participants in whom PNM will be applied to the femoral nerve of the non-pain knee | Other: PNM<br>* an asymmetric rectangular biphasic current (250 microseconds, 10 Hz)<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| visual analog scale (VAS) (0, no pain; 100, maximum pain). | pain | up to 1 week |
| range joint | goniometer | up to 1 week |
| VISA-p questionnaire (0, maximum pain; 100, no pain). | Functional pain | up to 1 week |
| Kujala questionnaire (0, maximum pain; 100, no pain). | Functional pain | up to 1 week |
|
||||
NCT03304132
|
The Oral Microbiome and Upper Aerodigestive Squamous Cell Cancer
|
The human oral cavity is a diverse habitat that contains approximately 700 prokaryotic species. The oral microbiome is comprised of 44% named species, 12% isolates representing unnamed species, and 44% phylotypes known only from 16S rRNA based cloning studies (http://www.homd.org/). Species from 11 phyla have been identified: Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, Spirochaetes, Fusobacteria, TM7, Synergistetes, Chlamydiae, Chloroflexi and SR1 (http://www.homd.org/). Because these observations have been mainly based on data generated from traditional Sanger sequencing, the diversity of oral microbiome is highly likely underestimated. Application of high throughput sequencing to the oral microbiome similar to the scale of the microbiome studies of other body sites (GI tract, skin, and vagina) under the Human Microbiome Project is necessary to obtain data essential for understanding the diversity and community structure of the oral microbiome in health and disease.
|
The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and The American Cancer Society Cancer Prevention Study II (CPS-II) investigators have identified 140 UADSCC cases that have been frequency matched 3:1 (420 controls) by incidence density sampling for study (ACS. PLCO), gender, ethnic background, and age, within 10 years.
|
The Oral Microbiome and Upper Aerodigestive Squamous Cell Cancer
|
Oral Cancer
|
* Other: Classification of Oral Microbiome Using 16S rRNA gene sequence-based approach
* Other: Classification of Oral Microbiome Using taxonomic approach
|
Inclusion Criteria:~Diagnosis of Upper Aerodigestive Squamous Cell Cancer and registered in:~The American Cancer Society Cancer Prevention Study II (CPS-II)~The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.
|
40 Years
|
92 Years
|
All
|
Accepts Healthy Volunteers
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 16S rRNA gene survey approach for microbiome characterization | Data alignment and clustering to determine microbiome species diversity | 4 Years |
|
Oral Microbiome, reflux disorders, esophageal microbiome, Alcohol Use, Tobacco Use
|
Mouth Neoplasms, Neoplasms, Squamous Cell, Carcinoma, Squamous Cell, Head and Neck Neoplasms, Neoplasms by Site, Neoplasms, Mouth Diseases, Stomatognathic Diseases, Neoplasms, Glandular and Epithelial, Neoplasms by Histologic Type, Carcinoma
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Upper aerodigestive squamous cell cancers (UADSCC) cases<br>From PLCO and ACS CPS II, identified 140 UADSCC cases. These cases are frequency matched 3:1 (420 controls) by incidence density sampling for study (ACS. PLCO), | Other: Classification of Oral Microbiome Using 16S rRNA gene sequence-based approach<br>* The sequence-based approach is selected because it classifies samples by considering the entire difference (genetic distance) in 16S rRNA gene sequences among samples analyzed, unbiased by artificial details such as taxonomies, sequence length, or even quality scores.<br>Other: Classification of Oral Microbiome Using taxonomic approach<br>* The taxonomic approach is a complement to the sequence-based approach in that it will further identify specific taxonomic groups or species that can explain the difference found by overall analyses.<br>|
| Controls<br>From PLCO and ACS CPS II, we have identified 140 UADSCC cases. These cases are frequency matched 3:1 (420 controls) by incidence density sampling for study (ACS. PLCO), | Other: Classification of Oral Microbiome Using 16S rRNA gene sequence-based approach<br>* The sequence-based approach is selected because it classifies samples by considering the entire difference (genetic distance) in 16S rRNA gene sequences among samples analyzed, unbiased by artificial details such as taxonomies, sequence length, or even quality scores.<br>Other: Classification of Oral Microbiome Using taxonomic approach<br>* The taxonomic approach is a complement to the sequence-based approach in that it will further identify specific taxonomic groups or species that can explain the difference found by overall analyses.<br>|
|
The Oral Microbiome and Upper Aerodigestive Squamous Cell Cancer
Study Overview
=================
Brief Summary
-----------------
The human oral cavity is a diverse habitat that contains approximately 700 prokaryotic species. The oral microbiome is comprised of 44% named species, 12% isolates representing unnamed species, and 44% phylotypes known only from 16S rRNA based cloning studies (http://www.homd.org/). Species from 11 phyla have been identified: Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, Spirochaetes, Fusobacteria, TM7, Synergistetes, Chlamydiae, Chloroflexi and SR1 (http://www.homd.org/). Because these observations have been mainly based on data generated from traditional Sanger sequencing, the diversity of oral microbiome is highly likely underestimated. Application of high throughput sequencing to the oral microbiome similar to the scale of the microbiome studies of other body sites (GI tract, skin, and vagina) under the Human Microbiome Project is necessary to obtain data essential for understanding the diversity and community structure of the oral microbiome in health and disease.
Detailed Description
-----------------
The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and The American Cancer Society Cancer Prevention Study II (CPS-II) investigators have identified 140 UADSCC cases that have been frequency matched 3:1 (420 controls) by incidence density sampling for study (ACS. PLCO), gender, ethnic background, and age, within 10 years.
Official Title
-----------------
The Oral Microbiome and Upper Aerodigestive Squamous Cell Cancer
Conditions
-----------------
Oral Cancer
Intervention / Treatment
-----------------
* Other: Classification of Oral Microbiome Using 16S rRNA gene sequence-based approach
* Other: Classification of Oral Microbiome Using taxonomic approach
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of Upper Aerodigestive Squamous Cell Cancer and registered in: The American Cancer Society Cancer Prevention Study II (CPS-II) The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.
Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 92 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Upper aerodigestive squamous cell cancers (UADSCC) cases<br>From PLCO and ACS CPS II, identified 140 UADSCC cases. These cases are frequency matched 3:1 (420 controls) by incidence density sampling for study (ACS. PLCO), | Other: Classification of Oral Microbiome Using 16S rRNA gene sequence-based approach<br>* The sequence-based approach is selected because it classifies samples by considering the entire difference (genetic distance) in 16S rRNA gene sequences among samples analyzed, unbiased by artificial details such as taxonomies, sequence length, or even quality scores.<br>Other: Classification of Oral Microbiome Using taxonomic approach<br>* The taxonomic approach is a complement to the sequence-based approach in that it will further identify specific taxonomic groups or species that can explain the difference found by overall analyses.<br>|
| Controls<br>From PLCO and ACS CPS II, we have identified 140 UADSCC cases. These cases are frequency matched 3:1 (420 controls) by incidence density sampling for study (ACS. PLCO), | Other: Classification of Oral Microbiome Using 16S rRNA gene sequence-based approach<br>* The sequence-based approach is selected because it classifies samples by considering the entire difference (genetic distance) in 16S rRNA gene sequences among samples analyzed, unbiased by artificial details such as taxonomies, sequence length, or even quality scores.<br>Other: Classification of Oral Microbiome Using taxonomic approach<br>* The taxonomic approach is a complement to the sequence-based approach in that it will further identify specific taxonomic groups or species that can explain the difference found by overall analyses.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 16S rRNA gene survey approach for microbiome characterization | Data alignment and clustering to determine microbiome species diversity | 4 Years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Oral Microbiome, reflux disorders, esophageal microbiome, Alcohol Use, Tobacco Use
|
||
NCT00908076
|
Amitiza in Constipation Associated With PD (Parkinson's Disease)
|
The purpose of this study is to determine if Amitiza (lubiprostone), a drug proven to be safe and effective for chronic constipation, will also improve constipation symptoms in Parkinson's Disease patients. We will also evaluate the impact of the drug on changes in bowel movement consistency, quality of life and motor symptoms.
|
Parkinson's disease (PD) affects about one million people in the United States. It is a common neurological condition that is clinically defined by rigidity (muscle stiffness), bradykinesia (slowness of movement) and tremor. Parkinson's Disease , however, reveals numerous non-motor symptoms that have been underemphasized. Problematic symptoms include varying degrees of dementia, psychosis, diminished assertiveness and confidence, general fatigue, excessive daytime sleepiness, problems with blood pressure, sweating, and bladder, and a common yet difficult to define sense of not feeling well.~A commonly missed symptom in Parkinson's patients is constipation. Constipation can be difficult to treat with current medications available and many are ineffective. Levodopa and dopamine agonists drugs are useful for motor symptoms in Parkinson's Disease but have no effect on constipation. Laxatives and enemas provide limited relief with bothersome side effects. Even fewer drugs have been studied targeting the constipation problem specifically in the Parkinson's Disease population. Lubiprostone (AMITIZA) is a new medication that has been studied in the general population for the treatment of chronic constipation. It has been shown to be a safe and effective medication with few side effects. Lubiprostone has not yet been studied in the Parkinson's Disease population. We hope to show that this medication can be safe and effective for constipation in PD patients as well.
|
Randomized Double-Blind Placebo-Controlled Trial of Lubiprostone in the Treatment of Constipation Associated With Parkinson's Disease
|
Parkinson's Disease
|
* Drug: LUBIPROSTONE
|
Inclusion Criteria:~1. Subjects must be diagnosed with PD according to conventional criteria.~2. Subjects must report having constipation and fulfill Rome III criteria19 for chronic constipation: at least 3 months, in the last 6 months with two or more of the following: i. Less than 3 SBM's per week ii. Straining with defecation more than 25% of the time iii. Lumpy or hard stools with defecation more than 25% of the time iv. Sensation of incomplete evacuation with defecation more than 25% of the time v. Sensation of anorectal obstruction or blockage with defecation more than 25% of the time vi. Use of manual maneuvers to facilitate defecation more than 25% of the time~3. Patients will be encouraged to use only lubiprostone for constipation. If they use any other agents they will need to record this use in their diary; any BM that occurs within 24 hours of the other agent used will be recorded, but not be counted as a SBM.~4. Patients or patients' caretaker(s)/ legal guardian must be able to read, understand, and accurately record data into the diary to guarantee full participation in the study.~5. Patients over the age of 50 must have had a colonoscopy or sigmoidoscopy within 5 years.~6. Patients or patient's caretaker(s)/legal guardian must be willing and able to provide informed consent before beginning the study.~Exclusion Criteria:~Evidence of structural abnormality of the gastrointestinal tract or diseases/conditions that affect bowel transit including gastric, small bowel or colonic resection (appendectomy, cholecystectomy, benign polypectomy are allowed); history of colon cancer, history of inflammatory bowel disease (Crohn's disease or ulcerative colitis); insulin-dependent diabetes mellitus, history of Hirschsprung's disease, progressive systemic sclerosis (scleroderma), anorexia nervosa; other diseases or conditions that in the opinion of the investigator significantly affect bowel transit. Subjects with constipation secondary to any other documented cause.~Planned use of drugs or agents during pretreatment phase onward that affect gastrointestinal motility and/ or prescription including laxatives including stool softeners (patients experiencing significant constipation may use a laxative as rescue medication if needed); antidiarrheals (in case of significant diarrhea loperamide may be used if needed); antacids containing magnesium or aluminum salts (only calcium containing ones are allowed); anticholinergics, antispasmodic agents (e.g., Librax, Donnatal, dicyclomine); erythromycin and other macrolides; octreotide; ondansetron or other 5-HT3 antagonists; opioids/narcotic analgesics; prokinetics (metoclopramide); serotonin re-uptake inhibitors or tricyclic antidepressants (allowed if constant doses for at least 1 month before treatment); calcium antagonists (allowed if constant doses for at least 1 month before treatment).~Subjects with any significant cardiovascular, liver, lung, renal, psychiatric or neurological diseases (not including PD).~Patients with previous allergic reaction or lack of tolerability to lubiprostone.~Current or recent history (within 12 months) of drug or alcohol abuse.~Pregnancy or breast feeding.~Fertile women (defined as those who are not surgically sterile, are not >1 year post-menopausal or who are not currently using or complying with a medically approved method of contraception). Lubiprostone has not been studied in pregnant women and should only be used during a pregnancy if the potential benefits justify the potential risk to the fetus. Women should have a negative pregnancy test before beginning treatment with lubiprostone and need to practice effective contraceptive measures
|
18 Years
|
85 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to End of Study | Global impression of change, stool diary, visual analog scale of improvement, UPDRS rating scale and constipation questionnaires. The primary efficacy data will be analyzed using Student's t-test with unequal variances as the difference from baseline in SBM comparing cases and controls, using last observation carried forward for missing data in the intent-to-treat population. | Baseline to end of study |
|
constipation, Parkinson's disease
|
Lubiprostone, Chloride Channel Agonists, Membrane Transport Modulators, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: amitiza<br>Amitiza | Drug: LUBIPROSTONE<br>* Subjects will be randomized into placebo and study groups. Half of the study group (N=39) will be given lubiprostone (24 mcg) twice daily; the other half will receive matching placebo twice daily.<br>|
| Placebo Comparator: Placebo<br>Matching Placebo | Drug: LUBIPROSTONE<br>* Subjects will be randomized into placebo and study groups. Half of the study group (N=39) will be given lubiprostone (24 mcg) twice daily; the other half will receive matching placebo twice daily.<br>|
|
Amitiza in Constipation Associated With PD (Parkinson's Disease)
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine if Amitiza (lubiprostone), a drug proven to be safe and effective for chronic constipation, will also improve constipation symptoms in Parkinson's Disease patients. We will also evaluate the impact of the drug on changes in bowel movement consistency, quality of life and motor symptoms.
Detailed Description
-----------------
Parkinson's disease (PD) affects about one million people in the United States. It is a common neurological condition that is clinically defined by rigidity (muscle stiffness), bradykinesia (slowness of movement) and tremor. Parkinson's Disease , however, reveals numerous non-motor symptoms that have been underemphasized. Problematic symptoms include varying degrees of dementia, psychosis, diminished assertiveness and confidence, general fatigue, excessive daytime sleepiness, problems with blood pressure, sweating, and bladder, and a common yet difficult to define sense of not feeling well. A commonly missed symptom in Parkinson's patients is constipation. Constipation can be difficult to treat with current medications available and many are ineffective. Levodopa and dopamine agonists drugs are useful for motor symptoms in Parkinson's Disease but have no effect on constipation. Laxatives and enemas provide limited relief with bothersome side effects. Even fewer drugs have been studied targeting the constipation problem specifically in the Parkinson's Disease population. Lubiprostone (AMITIZA) is a new medication that has been studied in the general population for the treatment of chronic constipation. It has been shown to be a safe and effective medication with few side effects. Lubiprostone has not yet been studied in the Parkinson's Disease population. We hope to show that this medication can be safe and effective for constipation in PD patients as well.
Official Title
-----------------
Randomized Double-Blind Placebo-Controlled Trial of Lubiprostone in the Treatment of Constipation Associated With Parkinson's Disease
Conditions
-----------------
Parkinson's Disease
Intervention / Treatment
-----------------
* Drug: LUBIPROSTONE
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1. Subjects must be diagnosed with PD according to conventional criteria. 2. Subjects must report having constipation and fulfill Rome III criteria19 for chronic constipation: at least 3 months, in the last 6 months with two or more of the following: i. Less than 3 SBM's per week ii. Straining with defecation more than 25% of the time iii. Lumpy or hard stools with defecation more than 25% of the time iv. Sensation of incomplete evacuation with defecation more than 25% of the time v. Sensation of anorectal obstruction or blockage with defecation more than 25% of the time vi. Use of manual maneuvers to facilitate defecation more than 25% of the time 3. Patients will be encouraged to use only lubiprostone for constipation. If they use any other agents they will need to record this use in their diary; any BM that occurs within 24 hours of the other agent used will be recorded, but not be counted as a SBM. 4. Patients or patients' caretaker(s)/ legal guardian must be able to read, understand, and accurately record data into the diary to guarantee full participation in the study. 5. Patients over the age of 50 must have had a colonoscopy or sigmoidoscopy within 5 years. 6. Patients or patient's caretaker(s)/legal guardian must be willing and able to provide informed consent before beginning the study. Exclusion Criteria: Evidence of structural abnormality of the gastrointestinal tract or diseases/conditions that affect bowel transit including gastric, small bowel or colonic resection (appendectomy, cholecystectomy, benign polypectomy are allowed); history of colon cancer, history of inflammatory bowel disease (Crohn's disease or ulcerative colitis); insulin-dependent diabetes mellitus, history of Hirschsprung's disease, progressive systemic sclerosis (scleroderma), anorexia nervosa; other diseases or conditions that in the opinion of the investigator significantly affect bowel transit. Subjects with constipation secondary to any other documented cause. Planned use of drugs or agents during pretreatment phase onward that affect gastrointestinal motility and/ or prescription including laxatives including stool softeners (patients experiencing significant constipation may use a laxative as rescue medication if needed); antidiarrheals (in case of significant diarrhea loperamide may be used if needed); antacids containing magnesium or aluminum salts (only calcium containing ones are allowed); anticholinergics, antispasmodic agents (e.g., Librax, Donnatal, dicyclomine); erythromycin and other macrolides; octreotide; ondansetron or other 5-HT3 antagonists; opioids/narcotic analgesics; prokinetics (metoclopramide); serotonin re-uptake inhibitors or tricyclic antidepressants (allowed if constant doses for at least 1 month before treatment); calcium antagonists (allowed if constant doses for at least 1 month before treatment). Subjects with any significant cardiovascular, liver, lung, renal, psychiatric or neurological diseases (not including PD). Patients with previous allergic reaction or lack of tolerability to lubiprostone. Current or recent history (within 12 months) of drug or alcohol abuse. Pregnancy or breast feeding. Fertile women (defined as those who are not surgically sterile, are not >1 year post-menopausal or who are not currently using or complying with a medically approved method of contraception). Lubiprostone has not been studied in pregnant women and should only be used during a pregnancy if the potential benefits justify the potential risk to the fetus. Women should have a negative pregnancy test before beginning treatment with lubiprostone and need to practice effective contraceptive measures
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: amitiza<br>Amitiza | Drug: LUBIPROSTONE<br>* Subjects will be randomized into placebo and study groups. Half of the study group (N=39) will be given lubiprostone (24 mcg) twice daily; the other half will receive matching placebo twice daily.<br>|
| Placebo Comparator: Placebo<br>Matching Placebo | Drug: LUBIPROSTONE<br>* Subjects will be randomized into placebo and study groups. Half of the study group (N=39) will be given lubiprostone (24 mcg) twice daily; the other half will receive matching placebo twice daily.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to End of Study | Global impression of change, stool diary, visual analog scale of improvement, UPDRS rating scale and constipation questionnaires. The primary efficacy data will be analyzed using Student's t-test with unequal variances as the difference from baseline in SBM comparing cases and controls, using last observation carried forward for missing data in the intent-to-treat population. | Baseline to end of study |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
constipation, Parkinson's disease
|
|
NCT00599677
|
Randomized Controlled Trial of Acupuncture for Functional Dyspepsia
|
The purpose of the study is to testify the efficacy of treating functional dyspepsia with acupuncture, and provide evidence for the hypothesis that Acupuncture effect is based on meridians, and gathering of meridian Qi is the key point.
|
The purpose of the study is to testify whether acupuncture is effective for functional dyspepsia, through treating functional dyspepsia patient for a month, using different acupoints according to literatures of treating migraine with acupuncture, and using Itopride as controlled group, and try to provide clinical evidence for the hypothesis thatAcupuncture effect is based on meridians, and gathering of meridian Qi is the key point.
|
Randomized Controlled Trial of Acupuncture for Functional Dyspepsia
|
Functional Dyspepsia
|
* Other: acupuncture
* Drug: Itopride
|
Inclusion Criteria:~Consistent with the diagnostic criteria of functional dyspepsia.~Age of a subject is older than 18 and is younger than 65.（including 18 and 65）~Did not take any gastroenteric dynamic drugs in the last 15 days, and did not take part in any clinical trial.~Informed consent is signed by a subject or his lineal relation.~Exclusion Criteria:~Patients with any contraindications of Itopride.~Patients who are unconscious, psychotic.~Patients with aggravating tumor and other serious consumptive disease, and who are subject to infection and bleeding.~With serious protopathy or disease of cardiovascular, liver, renal, gastrointestinal, hematological systems and so on.~Pregnant women or women in lactation.
|
18 Years
|
65 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nepean Dyspepsia Index | | 4 weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptoms Index of Dyspepsia | | 4 weeks |
|
acupuncture, meridian, acupoint
|
Dyspepsia, Signs and Symptoms, Digestive
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: group 1<br>specific acupoints of Stomach meridians | Other: acupuncture<br>* Subjects are treated five days a week continuously, and for four weeks.They are treated 30min every time.<br>|
| Experimental: group 2<br>Non-specific acupoints of Stomach meridians | Other: acupuncture<br>* Subjects are treated five days a week continuously, and for four weeks.They are treated 30min every time.<br>|
| Experimental: group 3<br>alarm and transport points | Other: acupuncture<br>* Subjects are treated five days a week continuously, and for four weeks.They are treated 30min every time.<br>|
| Experimental: group 4<br>acupoints of the other meridian | Other: acupuncture<br>* Subjects are treated five days a week continuously, and for four weeks.They are treated 30min every time.<br>|
| Sham Comparator: group 5<br>non-acupoints | Other: acupuncture<br>* Subjects are treated five days a week continuously, and for four weeks.They are treated 30min every time.<br>|
| Active Comparator: group 6<br>Itopride | Drug: Itopride<br>* Each pill weighs 50mg, once a pill, three times a day. The pills are taken half an hour before meals, and be taken 4 weeks continuously.<br>* Other names: Itopride Hydrochloride Tablets;|
|
Randomized Controlled Trial of Acupuncture for Functional Dyspepsia
Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to testify the efficacy of treating functional dyspepsia with acupuncture, and provide evidence for the hypothesis that Acupuncture effect is based on meridians, and gathering of meridian Qi is the key point.
Detailed Description
-----------------
The purpose of the study is to testify whether acupuncture is effective for functional dyspepsia, through treating functional dyspepsia patient for a month, using different acupoints according to literatures of treating migraine with acupuncture, and using Itopride as controlled group, and try to provide clinical evidence for the hypothesis thatAcupuncture effect is based on meridians, and gathering of meridian Qi is the key point.
Official Title
-----------------
Randomized Controlled Trial of Acupuncture for Functional Dyspepsia
Conditions
-----------------
Functional Dyspepsia
Intervention / Treatment
-----------------
* Other: acupuncture
* Drug: Itopride
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Consistent with the diagnostic criteria of functional dyspepsia. Age of a subject is older than 18 and is younger than 65.（including 18 and 65） Did not take any gastroenteric dynamic drugs in the last 15 days, and did not take part in any clinical trial. Informed consent is signed by a subject or his lineal relation. Exclusion Criteria: Patients with any contraindications of Itopride. Patients who are unconscious, psychotic. Patients with aggravating tumor and other serious consumptive disease, and who are subject to infection and bleeding. With serious protopathy or disease of cardiovascular, liver, renal, gastrointestinal, hematological systems and so on. Pregnant women or women in lactation.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: group 1<br>specific acupoints of Stomach meridians | Other: acupuncture<br>* Subjects are treated five days a week continuously, and for four weeks.They are treated 30min every time.<br>|
| Experimental: group 2<br>Non-specific acupoints of Stomach meridians | Other: acupuncture<br>* Subjects are treated five days a week continuously, and for four weeks.They are treated 30min every time.<br>|
| Experimental: group 3<br>alarm and transport points | Other: acupuncture<br>* Subjects are treated five days a week continuously, and for four weeks.They are treated 30min every time.<br>|
| Experimental: group 4<br>acupoints of the other meridian | Other: acupuncture<br>* Subjects are treated five days a week continuously, and for four weeks.They are treated 30min every time.<br>|
| Sham Comparator: group 5<br>non-acupoints | Other: acupuncture<br>* Subjects are treated five days a week continuously, and for four weeks.They are treated 30min every time.<br>|
| Active Comparator: group 6<br>Itopride | Drug: Itopride<br>* Each pill weighs 50mg, once a pill, three times a day. The pills are taken half an hour before meals, and be taken 4 weeks continuously.<br>* Other names: Itopride Hydrochloride Tablets;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nepean Dyspepsia Index | | 4 weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptoms Index of Dyspepsia | | 4 weeks |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
acupuncture, meridian, acupoint
|
NCT03957863
|
Study of Erythropoietin in Newborns and Children
|
Erythropoietin (EPO) is a glycoprotein hormone with a molecular weight of 30.4 kDa, responsible for regulating erythropoiesis in adults, newborns and fetuses. During pregnancy, the concentration of maternal serum EPO increases linearly to allow for effective erythropoiesis over time. In the fetus, in the first 30 weeks of gestation, the liver is the main synthetic organ. Thereafter, there is a progressive transfer of the synthesis of EPO to the kidneys. In the long term, under normal conditions of oxygenation, the fetal synthesis of EPO is mainly ensured by the kidney.~Because of the impossibility of making EPO tissue reserves and the inability of EPO to pass the placental barrier, the concentration of circulating EPO in the fetus reflects the balance between production and elimination. During the last trimester of pregnancy, in the absence of patent hypoxia, fetal concentrations of circulating EPO are between 10 and 50 mIU /ml, while in amniotic fluid the EPO is found at lower concentrations, between 2 and 20 mIU /ml.~In adults, EPO synthesis is primarily renal, and incidentally hepatic, even if in certain pathological situations (end-stage kidney disease or polycystosis) the liver is able to take over and synthesize EPO with an electrophoretic profile similar to that of the EPO from the umbilical cord, but often in insufficient quantities.~The objective of this study is to describe the forms of EPO in newborns and to compare possible iso-forms with those of adults.
|
Study of Erythropoietin in Newborns and Children
|
Newborn Infant, Child Under One Year of Age
|
* Biological: Plasma collection for EPO assay
|
Inclusion Criteria:~infant or child under 1 year old hospitalized or consulting at CHU Dijon Bourgogne whose parents have not opposed participation in the study~Exclusion Criteria:~child treated with recombinant erythropoietin
|
1 Month
|
12 Months
|
All
|
Accepts Healthy Volunteers
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EPO concentration UI/L | | Baseline |
| Electrophoretic profile of EPO | It is an indicator of glycosylation differences (more complex forms including sialic acids are more acidic, less complex forms are more basic) | Baseline |
|
| Intervention/Treatment |
| --- |
|Biological: Plasma collection for EPO assay|Plasma collection for EPO assay|
|
Study of Erythropoietin in Newborns and Children
Study Overview
=================
Brief Summary
-----------------
Erythropoietin (EPO) is a glycoprotein hormone with a molecular weight of 30.4 kDa, responsible for regulating erythropoiesis in adults, newborns and fetuses. During pregnancy, the concentration of maternal serum EPO increases linearly to allow for effective erythropoiesis over time. In the fetus, in the first 30 weeks of gestation, the liver is the main synthetic organ. Thereafter, there is a progressive transfer of the synthesis of EPO to the kidneys. In the long term, under normal conditions of oxygenation, the fetal synthesis of EPO is mainly ensured by the kidney. Because of the impossibility of making EPO tissue reserves and the inability of EPO to pass the placental barrier, the concentration of circulating EPO in the fetus reflects the balance between production and elimination. During the last trimester of pregnancy, in the absence of patent hypoxia, fetal concentrations of circulating EPO are between 10 and 50 mIU /ml, while in amniotic fluid the EPO is found at lower concentrations, between 2 and 20 mIU /ml. In adults, EPO synthesis is primarily renal, and incidentally hepatic, even if in certain pathological situations (end-stage kidney disease or polycystosis) the liver is able to take over and synthesize EPO with an electrophoretic profile similar to that of the EPO from the umbilical cord, but often in insufficient quantities. The objective of this study is to describe the forms of EPO in newborns and to compare possible iso-forms with those of adults.
Official Title
-----------------
Study of Erythropoietin in Newborns and Children
Conditions
-----------------
Newborn Infant, Child Under One Year of Age
Intervention / Treatment
-----------------
* Biological: Plasma collection for EPO assay
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: infant or child under 1 year old hospitalized or consulting at CHU Dijon Bourgogne whose parents have not opposed participation in the study Exclusion Criteria: child treated with recombinant erythropoietin
Ages Eligible for Study
-----------------
Minimum Age: 1 Month
Maximum Age: 12 Months
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Intervention/Treatment |
| --- |
|Biological: Plasma collection for EPO assay|Plasma collection for EPO assay|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EPO concentration UI/L | | Baseline |
| Electrophoretic profile of EPO | It is an indicator of glycosylation differences (more complex forms including sialic acids are more acidic, less complex forms are more basic) | Baseline |
|
|||||
NCT01596569
|
Combined Transcranial Magnetic Stimulation and Cognitive Treatment in Blast Traumatic Brain Injury
|
This study investigates the efficacy of a novel neurorehabilitation program combining noninvasive brain stimulation (transcranial magnetic stimulation or TMS) and cognitive therapy, on cognitive function and quality of life in individuals with blast-induced traumatic brain injury (bTBI).
|
The most common blast-induced traumatic brain injury (bTBI)-associated problems are cognitive deficits, such as executive functioning and memory. This study evaluates a combined rehabilitation program: transcranial magnetic stimulation (TMS) and cognitive therapy for treatment of patients with bTBI. TMS is a noninvasive way of stimulating the brain, which is not painful and does not involve any needles or any form of surgery. It acts by delivering a magnetic stimulation to a particular brain region. Half of the study participants will receive cognitive intervention with active TMS, and a control group will receive cognitive intervention with sham TMS. This study takes place in Boston, Massachusetts: at the VA Boston Healthcare System and Beth Israel Deaconess Medical Center.
|
Combining Cognitive Treatment With Noninvasive Brain Stimulation in Blast TBI
|
Traumatic Brain Injury, Cognitive Dysfunction, Blast Injury
|
* Device: Repetitive Transcranial Magnetic Stimulation (rTMS)
* Behavioral: Cognitive Intervention
|
Inclusion Criteria:~OEF/OIF active-duty personnel or veterans exposed to blast~Meets criteria for mild TBI~LOC of 30 min or less~Age: 21-50~Primary language is English~Exclusion Criteria:~Evidence of penetrating head injury~History of previous neurological diagnosis~History of previous psychotic disorder prior to the blast exposure~Hearing or vision impairment
|
21 Years
|
50 Years
|
All
|
No
|
Primary Purpose: Device Feasibility
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post concussive symptoms in TBI | Neurobehavioral Symptoms Inventory (NSI) is a 22-item measure that assesses the post-concussive symptoms in patients with TBI.The NSI asks the patient to rate each of the symptoms according to how much the symptom has disturbed him/her using a five point scale. Patient ratings are based on descriptions of the frequency of the symptom, the extent to which the symptom disrupts the patient's activities, and the patient's perceived need for help with the symptom. A total score will be summated. Lower scores are more favorable. | 4 weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daily life and functional outcome | Dysexecutive Questionnaire (DEX) is a 20-item self-report measure of real-life deficits relevant to cognitive/executive function that measures four domains: emotional, motivational, behavioral and cognitive. All items are rates in terms of frequency on a 5-point scale: 0 (never), 1(occasionally), 2 (sometimes), 3 (fairly often), 4 (very often). Scores are summed and the total scores range from 0 to 80, with higher scores indicating greater problems with executive functioning. | 4 weeks |
| PTSD symptoms | Military version (PCL-M) 17-item self-report measure that assesses PTSD symptoms. Each item is scored on the frequency of the problem from 1 to 5 where 1= not at all and 5= extremely. A total score is calculated and lower scores are more favorable.. | 4 weeks |
|
Blast Traumatic Brain Injury, Cognitive Rehabilitation, Transcranial Magnetic Stimulation, Combined Treatment
|
Brain Injuries, Brain Injuries, Traumatic, Wounds and Injuries, Blast Injuries, Cognitive Dysfunction, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Craniocerebral Trauma, Trauma, Nervous System, Cognition Disorders, Neurocognitive Disorders, Mental Disorders, Barotrauma
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active TMS and Cognitive Intervention<br>Active TMS and Cognitive Intervention:~Repetitive Transcranial Magnetic Stimulation (rTMS) and Cognitive intervention designed specifically to address the most common cognitive deficits (executive function and memory). | Device: Repetitive Transcranial Magnetic Stimulation (rTMS)<br>* Daily rTMS treatment for one week. Sham TMS participants receive the same study procedures as patients receiving active TMS.<br>* Other names: Magstim Corporation;Behavioral: Cognitive Intervention<br>* Cognitive intervention designed specifically to address the most common cognitive deficits (executive function and memory) in bTBI.~All participants receive weekly cognitive treatment sessions for 10 weeks.<br>* Other names: Cognitive Training;|
| Sham Comparator: Sham TMS and Cognitive Intervention:<br>Sham TMS and Cognitive Intervention:~Repetitive Transcranial Magnetic Stimulation (rTMS) and Cognitive intervention designed specifically to address the most common cognitive deficits (executive function and memory). | Device: Repetitive Transcranial Magnetic Stimulation (rTMS)<br>* Daily rTMS treatment for one week. Sham TMS participants receive the same study procedures as patients receiving active TMS.<br>* Other names: Magstim Corporation;Behavioral: Cognitive Intervention<br>* Cognitive intervention designed specifically to address the most common cognitive deficits (executive function and memory) in bTBI.~All participants receive weekly cognitive treatment sessions for 10 weeks.<br>* Other names: Cognitive Training;|
|
Combined Transcranial Magnetic Stimulation and Cognitive Treatment in Blast Traumatic Brain Injury
Study Overview
=================
Brief Summary
-----------------
This study investigates the efficacy of a novel neurorehabilitation program combining noninvasive brain stimulation (transcranial magnetic stimulation or TMS) and cognitive therapy, on cognitive function and quality of life in individuals with blast-induced traumatic brain injury (bTBI).
Detailed Description
-----------------
The most common blast-induced traumatic brain injury (bTBI)-associated problems are cognitive deficits, such as executive functioning and memory. This study evaluates a combined rehabilitation program: transcranial magnetic stimulation (TMS) and cognitive therapy for treatment of patients with bTBI. TMS is a noninvasive way of stimulating the brain, which is not painful and does not involve any needles or any form of surgery. It acts by delivering a magnetic stimulation to a particular brain region. Half of the study participants will receive cognitive intervention with active TMS, and a control group will receive cognitive intervention with sham TMS. This study takes place in Boston, Massachusetts: at the VA Boston Healthcare System and Beth Israel Deaconess Medical Center.
Official Title
-----------------
Combining Cognitive Treatment With Noninvasive Brain Stimulation in Blast TBI
Conditions
-----------------
Traumatic Brain Injury, Cognitive Dysfunction, Blast Injury
Intervention / Treatment
-----------------
* Device: Repetitive Transcranial Magnetic Stimulation (rTMS)
* Behavioral: Cognitive Intervention
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: OEF/OIF active-duty personnel or veterans exposed to blast Meets criteria for mild TBI LOC of 30 min or less Age: 21-50 Primary language is English Exclusion Criteria: Evidence of penetrating head injury History of previous neurological diagnosis History of previous psychotic disorder prior to the blast exposure Hearing or vision impairment
Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 50 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Device Feasibility
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active TMS and Cognitive Intervention<br>Active TMS and Cognitive Intervention: Repetitive Transcranial Magnetic Stimulation (rTMS) and Cognitive intervention designed specifically to address the most common cognitive deficits (executive function and memory). | Device: Repetitive Transcranial Magnetic Stimulation (rTMS)<br>* Daily rTMS treatment for one week. Sham TMS participants receive the same study procedures as patients receiving active TMS.<br>* Other names: Magstim Corporation;Behavioral: Cognitive Intervention<br>* Cognitive intervention designed specifically to address the most common cognitive deficits (executive function and memory) in bTBI. All participants receive weekly cognitive treatment sessions for 10 weeks.<br>* Other names: Cognitive Training;|
| Sham Comparator: Sham TMS and Cognitive Intervention:<br>Sham TMS and Cognitive Intervention: Repetitive Transcranial Magnetic Stimulation (rTMS) and Cognitive intervention designed specifically to address the most common cognitive deficits (executive function and memory). | Device: Repetitive Transcranial Magnetic Stimulation (rTMS)<br>* Daily rTMS treatment for one week. Sham TMS participants receive the same study procedures as patients receiving active TMS.<br>* Other names: Magstim Corporation;Behavioral: Cognitive Intervention<br>* Cognitive intervention designed specifically to address the most common cognitive deficits (executive function and memory) in bTBI. All participants receive weekly cognitive treatment sessions for 10 weeks.<br>* Other names: Cognitive Training;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post concussive symptoms in TBI | Neurobehavioral Symptoms Inventory (NSI) is a 22-item measure that assesses the post-concussive symptoms in patients with TBI.The NSI asks the patient to rate each of the symptoms according to how much the symptom has disturbed him/her using a five point scale. Patient ratings are based on descriptions of the frequency of the symptom, the extent to which the symptom disrupts the patient's activities, and the patient's perceived need for help with the symptom. A total score will be summated. Lower scores are more favorable. | 4 weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daily life and functional outcome | Dysexecutive Questionnaire (DEX) is a 20-item self-report measure of real-life deficits relevant to cognitive/executive function that measures four domains: emotional, motivational, behavioral and cognitive. All items are rates in terms of frequency on a 5-point scale: 0 (never), 1(occasionally), 2 (sometimes), 3 (fairly often), 4 (very often). Scores are summed and the total scores range from 0 to 80, with higher scores indicating greater problems with executive functioning. | 4 weeks |
| PTSD symptoms | Military version (PCL-M) 17-item self-report measure that assesses PTSD symptoms. Each item is scored on the frequency of the problem from 1 to 5 where 1= not at all and 5= extremely. A total score is calculated and lower scores are more favorable.. | 4 weeks |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Blast Traumatic Brain Injury, Cognitive Rehabilitation, Transcranial Magnetic Stimulation, Combined Treatment
|
NCT03240510
|
Understanding Male Breast Cancer: Salah Azaïz Cancer Institute Experience
|
The goal of this study is to evaluate the Salah Azaïz Cancer Institute male breast cancer patients population over a period of 14 years.~Goal of the retrospective part: to gather clinicopathologic data and follow-up outcomes of male breast cancer patients diagnosed and/or treated at Salah Azaïz Cancer Institute from 2004 to 2013.~Goal of the prospective part: to create a registry of male patients with breast cancer for a period of 48 months (from 2014 to 2017).
|
Understanding Male Breast Cancer: Salah Azaïz Cancer Institute Experience
|
Male Breast Cancer
|
Inclusion Criteria:~Histological diagnosis of male breast cancer
|
18 Years
| null |
Male
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical outcomes | Survival, Disease free survival | Through study completion, an average of 4 year |
| Clinico-biological characteristics of the disease | | Through study completion, an average of 4 year |
|
Breast cancer, Male
|
Breast Neoplasms, Breast Neoplasms, Male, Neoplasms by Site, Neoplasms, Breast Diseases, Skin Diseases
|
Understanding Male Breast Cancer: Salah Azaïz Cancer Institute Experience
Study Overview
=================
Brief Summary
-----------------
The goal of this study is to evaluate the Salah Azaïz Cancer Institute male breast cancer patients population over a period of 14 years. Goal of the retrospective part: to gather clinicopathologic data and follow-up outcomes of male breast cancer patients diagnosed and/or treated at Salah Azaïz Cancer Institute from 2004 to 2013. Goal of the prospective part: to create a registry of male patients with breast cancer for a period of 48 months (from 2014 to 2017).
Official Title
-----------------
Understanding Male Breast Cancer: Salah Azaïz Cancer Institute Experience
Conditions
-----------------
Male Breast Cancer
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histological diagnosis of male breast cancer
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
Male
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical outcomes | Survival, Disease free survival | Through study completion, an average of 4 year |
| Clinico-biological characteristics of the disease | | Through study completion, an average of 4 year |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Breast cancer, Male
|
|||||
NCT01753128
|
Efficacy of Imipramine for Treatment of Patients With Esophageal Hypersensitivity/ Functional Heartburn
|
Esophageal hypersensitivity/Functional heartburn are common among non-erosive reflux disease (NERD) patients who do not response to proton pump inhibitors. Whether tricyclic antidepressant improves NERD patient's symptoms remains unknown~Aim of this randomized controlled trial study is to determine the efficacy of imipramine, which could increase esophageal pain thresholds in healthy volunteers, in comparison with placebo for treatment patients with esophageal hypersensitivity or functional heartburn evaluated by improvement of specific-symptom score and quality of life
|
Efficacy of Imipramine for Treatment of Patients With Esophageal
|
Gastroesophageal Reflux Disease
|
* Drug: imipramine
|
Inclusion Criteria:~patient with typical reflux symptoms (heartburn and/or regurgitation) more than 3 times per week in at least last 3 months~Age more than 18 years~Upper GI endoscopy showed no esophageal mucosal breaks~MII-pH monitoring was not showed abnormal both acid and non-acid reflux~symptoms was not improved after received standard dose proton pump inhibitor for at least 1 month~Exclusion Criteria:~history of thoracic, esophagus, or stomach surgery~severe esophageal motility disorder eg. Achalasia, scleroderma, autonomic/peripheral neuropathy/myopathy~patient who was indicated to receive proton pump inhibitor~pregnant women~patient who was allergy to imipramine~patient who received tricyclic antidepressant or SSRI with in 3 month of enrollment
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| improvement of GERD score | | 6 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| improve quality of life | | 6 months |
|
Imipramine, Antidepressive Agents, Tricyclic, Antidepressive Agents, Psychotropic Drugs, Adrenergic Uptake Inhibitors, Neurotransmitter Uptake Inhibitors, Membrane Transport Modulators, Molecular Mechanisms of Pharmacological Action, Adrenergic Agents, Neurotransmitter Agents, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: imipramine<br> | Drug: imipramine<br> <br> |
|
Efficacy of Imipramine for Treatment of Patients With Esophageal Hypersensitivity/ Functional Heartburn
Study Overview
=================
Brief Summary
-----------------
Esophageal hypersensitivity/Functional heartburn are common among non-erosive reflux disease (NERD) patients who do not response to proton pump inhibitors. Whether tricyclic antidepressant improves NERD patient's symptoms remains unknown Aim of this randomized controlled trial study is to determine the efficacy of imipramine, which could increase esophageal pain thresholds in healthy volunteers, in comparison with placebo for treatment patients with esophageal hypersensitivity or functional heartburn evaluated by improvement of specific-symptom score and quality of life
Official Title
-----------------
Efficacy of Imipramine for Treatment of Patients With Esophageal
Conditions
-----------------
Gastroesophageal Reflux Disease
Intervention / Treatment
-----------------
* Drug: imipramine
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: patient with typical reflux symptoms (heartburn and/or regurgitation) more than 3 times per week in at least last 3 months Age more than 18 years Upper GI endoscopy showed no esophageal mucosal breaks MII-pH monitoring was not showed abnormal both acid and non-acid reflux symptoms was not improved after received standard dose proton pump inhibitor for at least 1 month Exclusion Criteria: history of thoracic, esophagus, or stomach surgery severe esophageal motility disorder eg. Achalasia, scleroderma, autonomic/peripheral neuropathy/myopathy patient who was indicated to receive proton pump inhibitor pregnant women patient who was allergy to imipramine patient who received tricyclic antidepressant or SSRI with in 3 month of enrollment
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: imipramine<br> | Drug: imipramine<br> <br> |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| improvement of GERD score | | 6 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| improve quality of life | | 6 months |
|
||
NCT00256659
|
Hospital Outcomes: Intervention in Moderately III Patients
|
To evaluate the utility of real time prognostic data (illness severity, stability and function) in the improvement of hospitalization morbidity, mortality, iatrogenic complications and length of stay.
|
To evaluate resource allocation and efficiency of ancillary service delivery in aggregate cost and 3 month follow up in regards to hospital readmission, living environment, and utilization of social services.~This is a randomized study which will compare the current Standard of Care in hospital to EARLY assessment and referrals with respect to social work services, rehabilitation, psychiatry, and nursing. In this study, the control group will receive the hospital support services provided under current system of delivery and allocation. The intervention group will not receive any new or different services not already provided to all patients at New York Presbyterian Hospital. The difference between the 2 groups will be the uniformity of screening to identify the needs of the patient in the respective area of social services, rehabilitation, psychiatric assistance, and nursing care, and the timeliness by which the referrals for support services will be placed.~Potential interventions: (In both control and experimental group)~Social work: Discharge planning (homecare, visiting nursing services, skilled nursing facility placement).~Rehabilitation: Physical Therapy (improve ADLs-activities of daily living).~Psychiatry: Diagnosis and Assistance in management of Depression.~Nursing: Prevention of in hospital falls and decubitus ulcer formation.
|
Hospital Outcomes: Intervention in Moderately III Patients
|
Moderately Ill Medical Inpatients at the Cornell Campus of the New York-Presbyterian Hospital
|
* Behavioral: Early assessment and referral to ancillary care services vs. standard care
|
Inclusion Criteria:~All medical in-patients who are coded moderately ill with fair to poor function in the SIGNOUT program will be asked to participate in our study.~Patients who are able to provide verbal consent for their participation will be enrolled.~Exclusion Criteria:~Any patient not coded in the SIGNOUT system as moderately ill with fair to poor function.~Patients who refuses not to participate in the study.~Patients who are unable to give written informed consent.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the utility of real time prognostic data and in the improvement of hospitalization morbidity, mortality, iatrogenic complications, and length of stay. | | |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate resource allocation and efficiency of ancillary service delivery in aggregate cost and 3 month follow up in regards to hospital readmission, living environment, and utilization of social services. | | |
|
Medical inpatients, Social Work, Physical therapy, Occupational therapy, Psychiatry, Early intervention, Iatrogenic complications
|
| Intervention/Treatment |
| --- |
|Behavioral: Early assessment and referral to ancillary care services vs. standard care|nan|
|
Hospital Outcomes: Intervention in Moderately III Patients
Study Overview
=================
Brief Summary
-----------------
To evaluate the utility of real time prognostic data (illness severity, stability and function) in the improvement of hospitalization morbidity, mortality, iatrogenic complications and length of stay.
Detailed Description
-----------------
To evaluate resource allocation and efficiency of ancillary service delivery in aggregate cost and 3 month follow up in regards to hospital readmission, living environment, and utilization of social services. This is a randomized study which will compare the current Standard of Care in hospital to EARLY assessment and referrals with respect to social work services, rehabilitation, psychiatry, and nursing. In this study, the control group will receive the hospital support services provided under current system of delivery and allocation. The intervention group will not receive any new or different services not already provided to all patients at New York Presbyterian Hospital. The difference between the 2 groups will be the uniformity of screening to identify the needs of the patient in the respective area of social services, rehabilitation, psychiatric assistance, and nursing care, and the timeliness by which the referrals for support services will be placed. Potential interventions: (In both control and experimental group) Social work: Discharge planning (homecare, visiting nursing services, skilled nursing facility placement). Rehabilitation: Physical Therapy (improve ADLs-activities of daily living). Psychiatry: Diagnosis and Assistance in management of Depression. Nursing: Prevention of in hospital falls and decubitus ulcer formation.
Official Title
-----------------
Hospital Outcomes: Intervention in Moderately III Patients
Conditions
-----------------
Moderately Ill Medical Inpatients at the Cornell Campus of the New York-Presbyterian Hospital
Intervention / Treatment
-----------------
* Behavioral: Early assessment and referral to ancillary care services vs. standard care
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All medical in-patients who are coded moderately ill with fair to poor function in the SIGNOUT program will be asked to participate in our study. Patients who are able to provide verbal consent for their participation will be enrolled. Exclusion Criteria: Any patient not coded in the SIGNOUT system as moderately ill with fair to poor function. Patients who refuses not to participate in the study. Patients who are unable to give written informed consent.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Intervention/Treatment |
| --- |
|Behavioral: Early assessment and referral to ancillary care services vs. standard care|nan|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the utility of real time prognostic data and in the improvement of hospitalization morbidity, mortality, iatrogenic complications, and length of stay. | | |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate resource allocation and efficiency of ancillary service delivery in aggregate cost and 3 month follow up in regards to hospital readmission, living environment, and utilization of social services. | | |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Medical inpatients, Social Work, Physical therapy, Occupational therapy, Psychiatry, Early intervention, Iatrogenic complications
|
|
NCT04204954
|
Evaluation of Treatment Option for Demodicosis in Patients Undergoing Cataract Surgery
|
Demodex blepharitis is a prevalent cause of comorbid infection among individuals undergoing cataract surgery. Several complications may arise in the postsurgical period from Staphylococcus or Streptococcus co-infections, as Demodex is a vector for these pathogens. Hence, prophylactic treatments before cataract surgery may lead to a reduction in complication rates. Since Demodex infestation and cataract surgery are two prevalent coexisting conditions in the general population, this study aims to test the effect of four combined treatments to eradicate or improve the Demodex infestation index before surgery. The investigators are conducting a single-blinded randomized trial of four therapies in participants undergoing cataract surgery. All participants will or are receiving daily eyelid cleansing bid and topical 0.3% ciprofloxacin q4h for three days added to the allocated treatment arm. Our four intervention groups are: [1] Blephaclean eye scrubs; [2] 50% dilution baby shampoo; [3] tea tree oil shampoo; [4]: topical 0.3% ciprofloxacin alone. To assess treatment efficacy, the investigators will perform eyelash hair epilation pre and postoperatively. The primary outcome is a change in the mean Demodex spp. infestation index. Also, a change in the crude number of Demodex (egg, larvae, nymph, or adult-form) spp. in eyelashes after one-week of therapy.
|
A Randomized Controlled Trial of Treatment Efficacy in Ameliorating Demodex Spp. Infestation Among Cases Undergoing Cataract Surgery
|
Demodex Infestation, Demodicosis, Cataract
|
* Other: Tea Tree Oil Shampoo
* Drug: Ciprofloxacin Ophthalmic Ointment 0.3%
* Other: Baby shampoo
* Other: Blephaclean
|
Inclusion Criteria:~Signed informed consent after explanation of the nature and possible consequences of the study.~Clinical diagnosis of cataracts staged with Lens Opacity Classification System III based on the American Academy of Ophthalmology and the American Society of Cataract and Refractive Surgery guidelines.~No topical antibiotic ointment therapy or eyelid cleansing in the past six months.~No systemic antibiotic or antiparasite treatment in the past six months.~No ocular comorbidities (other than cataracts)~No systemic comorbidities.~Exclusion Criteria:~Withdrawal from the study.~Minimal changes based on the Lens Opacity Classification System III.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients diagnosed with Demodex spp. infestation undergoing cataract surgery were randomly allocated into four comparison groups a control group (standard treatment) and three new modalities of Demodex therapy (Blephaclean, baby shampoo, and tea tree oil) + conventional treatment.
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Demodex spp. infestation index by intervention group | Number of demodex (egg, larvae, nymph, adult-form) spp. per eyelash (taken from epilation). | One week. |
| Crude count of Demodex spp. adult-forms (mites) in eyelashes by intervention group | Number of demodex (egg, larvae, nymph, adult-form) spp. in total (taken from epilation). | One week. |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endophthalmitis in the postoperative period. | Number of cases diagnosed with endophthalmitis in the postoperative period. | One week. |
|
Ciprofloxacin, Tea Tree Oil, Anti-Bacterial Agents, Anti-Infective Agents, Topoisomerase II Inhibitors, Topoisomerase Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action, Antineoplastic Agents, Cytochrome P-450 CYP1A2 Inhibitors, Cytochrome P-450 Enzyme Inhibitors, Anti-Infective Agents, Local
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Group 1: Topical 0.3% Ciprofloxacin [Cipro]<br>Ciprofloxacin Ophthalmic Ointment 0.3% every four hours for three days. | Drug: Ciprofloxacin Ophthalmic Ointment 0.3%<br>* Applied topically in the eyelid margin every four hours for three days.<br>|
| Active Comparator: Group 2: Cipro + 50% diluted baby shampoo<br>Ciprofloxacin Ophthalmic Ointment 0.3% every four hours for three days. Twice a day eyelid margin cleansing with 50% diluted baby shampoo for three days. | Drug: Ciprofloxacin Ophthalmic Ointment 0.3%<br>* Applied topically in the eyelid margin every four hours for three days.<br>Other: Baby shampoo<br>* Twice a day eyelid margin cleansing for three days.<br>* Other names: 50% diluted baby shampoo;|
| Active Comparator: Group 3: Cipro + Blephaclean<br>Ciprofloxacin Ophthalmic Ointment 0.3% every four hours for three days. Twice a day eyelid margin cleansing with Blephaclean Sterile Eyelid Wipes (Thea Pharmaceuticals) for three days. | Drug: Ciprofloxacin Ophthalmic Ointment 0.3%<br>* Applied topically in the eyelid margin every four hours for three days.<br>Other: Blephaclean<br>* Twice a day eyelid margin cleansing for three days.<br>|
| Experimental: Group 4: Cipro + Tea tree oil.<br>Ciprofloxacin Ophthalmic Ointment 0.3% every four hours for three days. Twice a day eyelid margin cleansing with tea tree oil shampoo for three days. | Other: Tea Tree Oil Shampoo<br>* Twice a day eyelid margin cleansing for three days.<br>Drug: Ciprofloxacin Ophthalmic Ointment 0.3%<br>* Applied topically in the eyelid margin every four hours for three days.<br>|
|
Evaluation of Treatment Option for Demodicosis in Patients Undergoing Cataract Surgery
Study Overview
=================
Brief Summary
-----------------
Demodex blepharitis is a prevalent cause of comorbid infection among individuals undergoing cataract surgery. Several complications may arise in the postsurgical period from Staphylococcus or Streptococcus co-infections, as Demodex is a vector for these pathogens. Hence, prophylactic treatments before cataract surgery may lead to a reduction in complication rates. Since Demodex infestation and cataract surgery are two prevalent coexisting conditions in the general population, this study aims to test the effect of four combined treatments to eradicate or improve the Demodex infestation index before surgery. The investigators are conducting a single-blinded randomized trial of four therapies in participants undergoing cataract surgery. All participants will or are receiving daily eyelid cleansing bid and topical 0.3% ciprofloxacin q4h for three days added to the allocated treatment arm. Our four intervention groups are: [1] Blephaclean eye scrubs; [2] 50% dilution baby shampoo; [3] tea tree oil shampoo; [4]: topical 0.3% ciprofloxacin alone. To assess treatment efficacy, the investigators will perform eyelash hair epilation pre and postoperatively. The primary outcome is a change in the mean Demodex spp. infestation index. Also, a change in the crude number of Demodex (egg, larvae, nymph, or adult-form) spp. in eyelashes after one-week of therapy.
Official Title
-----------------
A Randomized Controlled Trial of Treatment Efficacy in Ameliorating Demodex Spp. Infestation Among Cases Undergoing Cataract Surgery
Conditions
-----------------
Demodex Infestation, Demodicosis, Cataract
Intervention / Treatment
-----------------
* Other: Tea Tree Oil Shampoo
* Drug: Ciprofloxacin Ophthalmic Ointment 0.3%
* Other: Baby shampoo
* Other: Blephaclean
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed informed consent after explanation of the nature and possible consequences of the study. Clinical diagnosis of cataracts staged with Lens Opacity Classification System III based on the American Academy of Ophthalmology and the American Society of Cataract and Refractive Surgery guidelines. No topical antibiotic ointment therapy or eyelid cleansing in the past six months. No systemic antibiotic or antiparasite treatment in the past six months. No ocular comorbidities (other than cataracts) No systemic comorbidities. Exclusion Criteria: Withdrawal from the study. Minimal changes based on the Lens Opacity Classification System III.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients diagnosed with Demodex spp. infestation undergoing cataract surgery were randomly allocated into four comparison groups a control group (standard treatment) and three new modalities of Demodex therapy (Blephaclean, baby shampoo, and tea tree oil) + conventional treatment.
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Group 1: Topical 0.3% Ciprofloxacin [Cipro]<br>Ciprofloxacin Ophthalmic Ointment 0.3% every four hours for three days. | Drug: Ciprofloxacin Ophthalmic Ointment 0.3%<br>* Applied topically in the eyelid margin every four hours for three days.<br>|
| Active Comparator: Group 2: Cipro + 50% diluted baby shampoo<br>Ciprofloxacin Ophthalmic Ointment 0.3% every four hours for three days. Twice a day eyelid margin cleansing with 50% diluted baby shampoo for three days. | Drug: Ciprofloxacin Ophthalmic Ointment 0.3%<br>* Applied topically in the eyelid margin every four hours for three days.<br>Other: Baby shampoo<br>* Twice a day eyelid margin cleansing for three days.<br>* Other names: 50% diluted baby shampoo;|
| Active Comparator: Group 3: Cipro + Blephaclean<br>Ciprofloxacin Ophthalmic Ointment 0.3% every four hours for three days. Twice a day eyelid margin cleansing with Blephaclean Sterile Eyelid Wipes (Thea Pharmaceuticals) for three days. | Drug: Ciprofloxacin Ophthalmic Ointment 0.3%<br>* Applied topically in the eyelid margin every four hours for three days.<br>Other: Blephaclean<br>* Twice a day eyelid margin cleansing for three days.<br>|
| Experimental: Group 4: Cipro + Tea tree oil.<br>Ciprofloxacin Ophthalmic Ointment 0.3% every four hours for three days. Twice a day eyelid margin cleansing with tea tree oil shampoo for three days. | Other: Tea Tree Oil Shampoo<br>* Twice a day eyelid margin cleansing for three days.<br>Drug: Ciprofloxacin Ophthalmic Ointment 0.3%<br>* Applied topically in the eyelid margin every four hours for three days.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Demodex spp. infestation index by intervention group | Number of demodex (egg, larvae, nymph, adult-form) spp. per eyelash (taken from epilation). | One week. |
| Crude count of Demodex spp. adult-forms (mites) in eyelashes by intervention group | Number of demodex (egg, larvae, nymph, adult-form) spp. in total (taken from epilation). | One week. |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endophthalmitis in the postoperative period. | Number of cases diagnosed with endophthalmitis in the postoperative period. | One week. |
|
||
NCT01143480
|
Study of the Effect of Innate on the Inflammatory Response to Endotoxin
|
Background:~- Innate immunity is the process by which white blood cells and other parts of the immune system sense and respond to potential infections by causing an inflammation. Researchers are interested in studying how the body responds to certain environmental factors, and whether the body s response can contribute to chronic illnesses or diseases such as asthma and certain types of cancers.~Objectives:~- To examine how specific genes and proteins in blood cells respond to environmental exposures.~Eligibility:~- Healthy volunteers between 18 and 45 years of age.~Design:~The study will involve one visit of 45 to 60 minutes.~Participants will be screened with a brief physical examination and finger stick to determine if they are eligible to donate blood for the study, and will complete a questionnaire about any medications or other drugs (e.g., cigarettes) they may be taking.~Participants will provide a blood sample for research purposes.
|
This research study will examine the role of innate immunity on the Inflammatory response of monocytes and macrophages to endotoxin. Approximately 1450 healthy participants aged 18 years and older will be identified and recruited from the Environmental Polymorphism Registry (EPR). The EPR is a long-term project to collect and store up to 15,000 DNA samples for use in research studies from individuals in the greater North Carolina Triangle Region. It is anticipated that approximately 50% of the participants contacted will enroll and about 15% of participants enrolled will withdraw.~This controlled, observational gene association study will recruit participants on the basis of genotype and then observe the phenotype of each participant. There are several SNPs of interest in the genes TIRAP, MyD88, ABCA1, CD14, CD44, ITIH3, ITIH4, TLR4, TNFa, TLR5, IRGM, and APOL1. In addition there are alleles of interest in the gene ApoE. These alleles taken together are considered a polymorphism. For each polymorphism of interest a separate group of participants will be recruited (including heterozygous and homozygous for both the minor and major alleles for each SNP). A maximum of 200 mLs of blood will be obtained from each participant during one visit lasting approximately 1-1.5 hours. Blood monocytes will be isolated from the donated blood samples and cultured to obtain macrophages. The macrophages will be exposed ex vivo to an endotoxin (LPS) and to PAM3CSK4 to determine cell response depending on genotype. In studies of APOL1, a urine specimen will also be collected to evaluate for protein filtration.~The primary objective is to determine associations between select polymorphisms in genes [TIRAP (TIR Associated Protein), MyD88 (Myeloid Differentiation Primary Response Protein 88), ApoE (Apolipoprotein E), ABCA1 (ATP Binding Cassette Transporter A1), CD14, CD44, ITIH3, ITIH4, TLR4, TNFa, TLR5, IRGM, and APOL1] and quantitative in vitro inflammatory functions of two cell types, the macrophage and neutrophil. The primary endpoints of this study for both cell types will be levels of 6 cytokines TNF alpha, IL-6, MIP-2, IL-8, MCP-1, and IFN-beta (ELISA) induced by LPS and by PAM3CSK4 plus baseline cytokine levels (no exposure to LPS or PAM3CSK4). Urinary levels of protein will be quantified in some studies as a measure of early kidney dysfunction.~We hope the results of this study may lead to discovery of important information regarding the role of MDC1 (Mediator of DNA damage Checkpoint protein 1) in human disease, potentially identifying new targets for future studies.
|
Study of the Effect of Innate Immunity on the Inflammatory Response to Endotoxin
|
Asthma, Atherosclerosis, Metabolic Syndrome, Insulin Resistance, Cancer
|
INCLUSION CRITERIA:~Male or female 18 years of age or older~Participants must be able to understand and provide written informed consent to participate in the study~Participants must be able to travel to the CRU~Willing and able to fast after midnight the night prior to their study appointment~Healthy participants as defined by the International Red Cross guidelines (Healthy means that an individual feels well and can perform normal activities. If the individual has a chronic condition such as diabetes or high blood pressure, healthy also means that they are being treated and the condition is under control).~EXCLUSION CRITERIA:~Use of nonsteroidal anti-inflammatory drugs (NSAIDs) within 5 days prior to enrollment visit (e.g., Motrin, ibuprofen, naproxen, and Advil)~Use of acetaminophen (Tylenol) within 5 days prior to enrollment visit~Use of cholesterol lowering drugs (statins) within 30 days prior to enrollment visit (e.g., Zocor, Mevacor, Lipitor, and Crestor)~Use of immunosuppressants or other immune-modifying drugs [e.g., Rituxan, Humira, Enbrel, Cyclosporin (Neoral, Sandimmune, and SangCya), and Azathioprine (Imuran)], Monoclonal antibodies [e.g., infliximab (Remicade)], and corticosteroids (e.g., prednisone, prednisolone and dexamethasone)~Current treatment for cancer with chemotherapy or radiation~Confirmed or suspected immunosuppressive or immunodeficient condition~GI or respiratory Illness within 5 days prior to enrollment visit, including cold or allergies~Smoked tobacco, chewed tobacco or used electronic cigarettes within 2 weeks prior to enrollment visit (for participants who provide a urine specimen, this will be defined by urine cotinine >200 ng/mL at visit)~Alcohol consumption greater than 2 standard drinks (1 standard drink contains 15 g of ethanol) per day within the last 24 hours prior to the enrollment visit~Body weight < 50 kg (<110 lbs)~Temperature > 37.6 C; blood pressure < 90/50 mm Hg or > 170/95 mm Hg; pulse rate < 50 or >100 beats/minute~Pregnant or suspected pregnancy~Chronic Kidney Disease~The PI may review medication use on a case by case basis and make a medical determination on the participant s eligibility. In these cases, the PI determination will be documented in the participant s chart.
|
18 Years
|
100 Years
|
All
|
Accepts Healthy Volunteers
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoints of this study are for both cell types and will be levels of 6 cytokines [TNF alpha, IL-6, MIP-2, IL-8, MCP-1, and IFN-beta (ELISA)] induced by LPS and by PAM3CSK4 plus baseline cytokine levels (no exposure to LPS or PAM3CSK... | The primary endpoints of this study are for both cell types and will be levels of 6 cytokines [TNF alpha, IL-6, MIP-2, IL-8, MCP-1, and IFN-beta (ELISA)] induced by LPS and by PAM3CSK4 plus baseline cytokine levels (no exposure to LPS or PAM3CSK4). | After analysis |
|
Endotoxin, Innate Immunity, Natural History, Healthy Volunteer, HV
|
Atherosclerosis, Metabolic Syndrome, Insulin Resistance, Hyperinsulinism, Glucose Metabolism Disorders, Metabolic Diseases, Arteriosclerosis, Arterial Occlusive Diseases, Vascular Diseases, Cardiovascular Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| ABCA1<br>SNP or allele of interest | |
| APOE<br>SNP or allele of interest | |
| APOL1<br>SNP or allele of interest | |
| CD14<br>SNP or allele of interest | |
| CD44<br>SNP or allele of interest | |
| IRGM<br>SNP or allele of interest | |
| ITIH3<br>SNP or allele of interest | |
| ITIH4<br>SNP or allele of interest | |
| MyD88<br>SNP or allele of interest | |
| TIRAP<br>SNP or allele of interest | |
| TLR4<br>SNP or allele of interest | |
| TLR5<br>SNP or allele of interest | |
| TNFa<br>SNP or allele of interest | |
|
Study of the Effect of Innate on the Inflammatory Response to Endotoxin
Study Overview
=================
Brief Summary
-----------------
Background: - Innate immunity is the process by which white blood cells and other parts of the immune system sense and respond to potential infections by causing an inflammation. Researchers are interested in studying how the body responds to certain environmental factors, and whether the body s response can contribute to chronic illnesses or diseases such as asthma and certain types of cancers. Objectives: - To examine how specific genes and proteins in blood cells respond to environmental exposures. Eligibility: - Healthy volunteers between 18 and 45 years of age. Design: The study will involve one visit of 45 to 60 minutes. Participants will be screened with a brief physical examination and finger stick to determine if they are eligible to donate blood for the study, and will complete a questionnaire about any medications or other drugs (e.g., cigarettes) they may be taking. Participants will provide a blood sample for research purposes.
Detailed Description
-----------------
This research study will examine the role of innate immunity on the Inflammatory response of monocytes and macrophages to endotoxin. Approximately 1450 healthy participants aged 18 years and older will be identified and recruited from the Environmental Polymorphism Registry (EPR). The EPR is a long-term project to collect and store up to 15,000 DNA samples for use in research studies from individuals in the greater North Carolina Triangle Region. It is anticipated that approximately 50% of the participants contacted will enroll and about 15% of participants enrolled will withdraw. This controlled, observational gene association study will recruit participants on the basis of genotype and then observe the phenotype of each participant. There are several SNPs of interest in the genes TIRAP, MyD88, ABCA1, CD14, CD44, ITIH3, ITIH4, TLR4, TNFa, TLR5, IRGM, and APOL1. In addition there are alleles of interest in the gene ApoE. These alleles taken together are considered a polymorphism. For each polymorphism of interest a separate group of participants will be recruited (including heterozygous and homozygous for both the minor and major alleles for each SNP). A maximum of 200 mLs of blood will be obtained from each participant during one visit lasting approximately 1-1.5 hours. Blood monocytes will be isolated from the donated blood samples and cultured to obtain macrophages. The macrophages will be exposed ex vivo to an endotoxin (LPS) and to PAM3CSK4 to determine cell response depending on genotype. In studies of APOL1, a urine specimen will also be collected to evaluate for protein filtration. The primary objective is to determine associations between select polymorphisms in genes [TIRAP (TIR Associated Protein), MyD88 (Myeloid Differentiation Primary Response Protein 88), ApoE (Apolipoprotein E), ABCA1 (ATP Binding Cassette Transporter A1), CD14, CD44, ITIH3, ITIH4, TLR4, TNFa, TLR5, IRGM, and APOL1] and quantitative in vitro inflammatory functions of two cell types, the macrophage and neutrophil. The primary endpoints of this study for both cell types will be levels of 6 cytokines TNF alpha, IL-6, MIP-2, IL-8, MCP-1, and IFN-beta (ELISA) induced by LPS and by PAM3CSK4 plus baseline cytokine levels (no exposure to LPS or PAM3CSK4). Urinary levels of protein will be quantified in some studies as a measure of early kidney dysfunction. We hope the results of this study may lead to discovery of important information regarding the role of MDC1 (Mediator of DNA damage Checkpoint protein 1) in human disease, potentially identifying new targets for future studies.
Official Title
-----------------
Study of the Effect of Innate Immunity on the Inflammatory Response to Endotoxin
Conditions
-----------------
Asthma, Atherosclerosis, Metabolic Syndrome, Insulin Resistance, Cancer
Participation Criteria
=================
Eligibility Criteria
-----------------
INCLUSION CRITERIA: Male or female 18 years of age or older Participants must be able to understand and provide written informed consent to participate in the study Participants must be able to travel to the CRU Willing and able to fast after midnight the night prior to their study appointment Healthy participants as defined by the International Red Cross guidelines (Healthy means that an individual feels well and can perform normal activities. If the individual has a chronic condition such as diabetes or high blood pressure, healthy also means that they are being treated and the condition is under control). EXCLUSION CRITERIA: Use of nonsteroidal anti-inflammatory drugs (NSAIDs) within 5 days prior to enrollment visit (e.g., Motrin, ibuprofen, naproxen, and Advil) Use of acetaminophen (Tylenol) within 5 days prior to enrollment visit Use of cholesterol lowering drugs (statins) within 30 days prior to enrollment visit (e.g., Zocor, Mevacor, Lipitor, and Crestor) Use of immunosuppressants or other immune-modifying drugs [e.g., Rituxan, Humira, Enbrel, Cyclosporin (Neoral, Sandimmune, and SangCya), and Azathioprine (Imuran)], Monoclonal antibodies [e.g., infliximab (Remicade)], and corticosteroids (e.g., prednisone, prednisolone and dexamethasone) Current treatment for cancer with chemotherapy or radiation Confirmed or suspected immunosuppressive or immunodeficient condition GI or respiratory Illness within 5 days prior to enrollment visit, including cold or allergies Smoked tobacco, chewed tobacco or used electronic cigarettes within 2 weeks prior to enrollment visit (for participants who provide a urine specimen, this will be defined by urine cotinine >200 ng/mL at visit) Alcohol consumption greater than 2 standard drinks (1 standard drink contains 15 g of ethanol) per day within the last 24 hours prior to the enrollment visit Body weight < 50 kg (<110 lbs) Temperature > 37.6 C; blood pressure < 90/50 mm Hg or > 170/95 mm Hg; pulse rate < 50 or >100 beats/minute Pregnant or suspected pregnancy Chronic Kidney Disease The PI may review medication use on a case by case basis and make a medical determination on the participant s eligibility. In these cases, the PI determination will be documented in the participant s chart.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 100 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| ABCA1<br>SNP or allele of interest | |
| APOE<br>SNP or allele of interest | |
| APOL1<br>SNP or allele of interest | |
| CD14<br>SNP or allele of interest | |
| CD44<br>SNP or allele of interest | |
| IRGM<br>SNP or allele of interest | |
| ITIH3<br>SNP or allele of interest | |
| ITIH4<br>SNP or allele of interest | |
| MyD88<br>SNP or allele of interest | |
| TIRAP<br>SNP or allele of interest | |
| TLR4<br>SNP or allele of interest | |
| TLR5<br>SNP or allele of interest | |
| TNFa<br>SNP or allele of interest | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoints of this study are for both cell types and will be levels of 6 cytokines [TNF alpha, IL-6, MIP-2, IL-8, MCP-1, and IFN-beta (ELISA)] induced by LPS and by PAM3CSK4 plus baseline cytokine levels (no exposure to LPS or PAM3CSK... | The primary endpoints of this study are for both cell types and will be levels of 6 cytokines [TNF alpha, IL-6, MIP-2, IL-8, MCP-1, and IFN-beta (ELISA)] induced by LPS and by PAM3CSK4 plus baseline cytokine levels (no exposure to LPS or PAM3CSK4). | After analysis |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Endotoxin, Innate Immunity, Natural History, Healthy Volunteer, HV
|
|||
NCT01276574
|
Epithelial Ovarian Cancer- Staging and Response to Chemotherapy Evaluated by PET/CT
|
The purpose of this study is to determine, whether there is clinical benefit of using fdg-PET/CT (F-18-fluorodeoxyglucose- positron emission tomography/computed tomography)compared to contrast-enhanced CT in primary treatment of advanced epithelial ovarian cancer (EOC)~Objectives~the impact of preoperative PET/CT compared to CT on EOC stage definition~to compare the value of preoperative PET/CT, CT and laparoscopy in intra-abdominal tumour assessment. Laparotomy findings evaluated by surgeon and histopathologic results serve as the reference standard.~to compare serum markers HE4(human epididymis protein 4) and CA125 (cancer antigen 125) with FDG-PET/CT and CT in treatment response evaluation during neoadjuvant chemotherapy and primary treatment of EOC~to compare FDG PET/CT based treatment response evaluation with RECIST and GCIG criteria~Methods~All the patients will undergo FDG-PET/CT prior surgery, after possible neoadjuvant chemotherapy (NACT) and 4 weeks after completion of primary platinum-based chemotherapy.~CA125 and HE4 levels are measured pre-operatively, with every chemotherapy cycle and regularly during follow-up until 1st disease relapse
|
Epithelial Ovarian Cancer- Staging and Response to Chemotherapy Evaluated by PET/CT(Positron Emission Tomography/Computed Tomography)
|
Epithelial Ovarian Cancer, Peritoneal Cancer, Fallopian Tube Cancer
|
Inclusion Criteria:~Newly diagnosed patients with advanced epithelial ovarian, primary peritoneal cancer or fallopian tube cancer.~age 18-79 years~informed concent~Exclusion Criteria:~diabetes (for PET/CT analyses)~previous cancer
|
18 Years
|
79 Years
|
Female
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PET/CT (positron emission tomography/computed tomography)compared with contrast-enhanced CT in preoperative evaluation of disease burden in patients with advanced Epithelial ovarian cancer (EOC). | Patient is scanned with whole body Fdg PET/CT and contrast-enhanced CT in a row within 3 weeks preoperatively. Findings are compared with intraoperative surgical status evaluated by operator and confirmed with biopsies. | PET/CT, contrast-enhanced CT and surgical status and histopathological findings are compared 1 month after surgery |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neoadjuvant chemotherapy (NACT) response evaluation with PET/CT compared with contrast-enhanced CT after 3 cycles of chemotherapy | Fdg PET/CT and a contrast-enhanced CT are performed in a row at the time of diagnosis and repeated after 3 cycles of chemotherapy. Finding are compared with disease status in the interval debulking surgery evaluated by operator and histological specimen. | Outcome measure: after interval debulking surgery, about 4 months |
| Serial measurement of HE4 (human epididymis protein 4) and CA125 (cancer antigen 125)during primary treatment of EOC (Epithelial ovarian cancer) | HE4 and CA125 are measured at the time of diagnosis, perioperatively, and at each chemotherapy cycle (6-9). Treatment outcome is evaluated with contrast-enhanced CT at the end of primary therapy. HE4 and CA125 are compared with each other in different treatment outcomes (complete response, partial response, stable disease and progression) and PFS and OS | From diagnosis until the end of EOC primary therapy, about 8 months |
| Response to first line treatment: evaluation with PET/CT | Treatment outcome measured with RECIST 1.1 and GCIG criteria is compared with PET/CT results. The prognostic role of persistent metabolic activity in PET/CT is evaluated. | PET/CT taken about 4 weeks after the last chemotherapy cycle |
| HE4 and CA125 in 1st relapse | Prognostic value of HE4 and CA125 at 1st recurrence (defined with RECIST1.1. and GCIG criteria) is evaluated against post progression survival | Long time follow up ad 10 years |
|
PET/CT, Ovarian cancer, HE4
|
Ovarian Neoplasms, Carcinoma, Ovarian Epithelial, Fallopian Tube Neoplasms, Endocrine Gland Neoplasms, Neoplasms by Site, Neoplasms, Ovarian Diseases, Adnexal Diseases, Genital Diseases, Female, Female Urogenital Diseases, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases, Genital Neoplasms, Female, Urogenital Neoplasms, Genital Diseases, Endocrine System Diseases, Gonadal Disorders, Carcinoma, Neoplasms, Glandular and Epithelial, Neoplasms by Histologic Type, Fallopian Tube Diseases
|
Epithelial Ovarian Cancer- Staging and Response to Chemotherapy Evaluated by PET/CT
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine, whether there is clinical benefit of using fdg-PET/CT (F-18-fluorodeoxyglucose- positron emission tomography/computed tomography)compared to contrast-enhanced CT in primary treatment of advanced epithelial ovarian cancer (EOC) Objectives the impact of preoperative PET/CT compared to CT on EOC stage definition to compare the value of preoperative PET/CT, CT and laparoscopy in intra-abdominal tumour assessment. Laparotomy findings evaluated by surgeon and histopathologic results serve as the reference standard. to compare serum markers HE4(human epididymis protein 4) and CA125 (cancer antigen 125) with FDG-PET/CT and CT in treatment response evaluation during neoadjuvant chemotherapy and primary treatment of EOC to compare FDG PET/CT based treatment response evaluation with RECIST and GCIG criteria Methods All the patients will undergo FDG-PET/CT prior surgery, after possible neoadjuvant chemotherapy (NACT) and 4 weeks after completion of primary platinum-based chemotherapy. CA125 and HE4 levels are measured pre-operatively, with every chemotherapy cycle and regularly during follow-up until 1st disease relapse
Official Title
-----------------
Epithelial Ovarian Cancer- Staging and Response to Chemotherapy Evaluated by PET/CT(Positron Emission Tomography/Computed Tomography)
Conditions
-----------------
Epithelial Ovarian Cancer, Peritoneal Cancer, Fallopian Tube Cancer
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Newly diagnosed patients with advanced epithelial ovarian, primary peritoneal cancer or fallopian tube cancer. age 18-79 years informed concent Exclusion Criteria: diabetes (for PET/CT analyses) previous cancer
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 79 Years
Sexes Eligible for Study
-----------------
Female
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PET/CT (positron emission tomography/computed tomography)compared with contrast-enhanced CT in preoperative evaluation of disease burden in patients with advanced Epithelial ovarian cancer (EOC). | Patient is scanned with whole body Fdg PET/CT and contrast-enhanced CT in a row within 3 weeks preoperatively. Findings are compared with intraoperative surgical status evaluated by operator and confirmed with biopsies. | PET/CT, contrast-enhanced CT and surgical status and histopathological findings are compared 1 month after surgery |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neoadjuvant chemotherapy (NACT) response evaluation with PET/CT compared with contrast-enhanced CT after 3 cycles of chemotherapy | Fdg PET/CT and a contrast-enhanced CT are performed in a row at the time of diagnosis and repeated after 3 cycles of chemotherapy. Finding are compared with disease status in the interval debulking surgery evaluated by operator and histological specimen. | Outcome measure: after interval debulking surgery, about 4 months |
| Serial measurement of HE4 (human epididymis protein 4) and CA125 (cancer antigen 125)during primary treatment of EOC (Epithelial ovarian cancer) | HE4 and CA125 are measured at the time of diagnosis, perioperatively, and at each chemotherapy cycle (6-9). Treatment outcome is evaluated with contrast-enhanced CT at the end of primary therapy. HE4 and CA125 are compared with each other in different treatment outcomes (complete response, partial response, stable disease and progression) and PFS and OS | From diagnosis until the end of EOC primary therapy, about 8 months |
| Response to first line treatment: evaluation with PET/CT | Treatment outcome measured with RECIST 1.1 and GCIG criteria is compared with PET/CT results. The prognostic role of persistent metabolic activity in PET/CT is evaluated. | PET/CT taken about 4 weeks after the last chemotherapy cycle |
| HE4 and CA125 in 1st relapse | Prognostic value of HE4 and CA125 at 1st recurrence (defined with RECIST1.1. and GCIG criteria) is evaluated against post progression survival | Long time follow up ad 10 years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
PET/CT, Ovarian cancer, HE4
|
||||
NCT02028104
|
Stem Cell Therapy in Traumatic Brain Injury
|
The purpose of this study was to study the effect of stem cell therapy on common symptoms in patients with Traumatic Brain Injury
|
Open Label Study of Autologous Bone Marrow Mononuclear Cells in Traumatic Brain Injury
|
Traumatic Brain Injury
|
* Biological: Autologous bone marrow mononuclear cell transplantation
|
Inclusion Criteria:~Diagnosed cases of chronic traumatic brain injury~Age above 6 months~Exclusion Criteria:~presence of acute infections such as Human immunodeficiency virus/Hepatitis B - Virus/Hepatitis C Virus~malignancies~bleeding tendencies~pneumonia~renal failure~severe liver dysfunction~severe anemia [Hemoglobin < 8]~any bone marrow disorder~space occupying lesion in brain~other acute medical conditions such as respiratory infection and pyrexia~pregnancy~lactation
|
6 Months
|
65 Years
|
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in clinical symptoms of traumatic brain injury | | 6 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disability Rating scale | | 6 months |
|
Brain Injuries, Brain Injuries, Traumatic, Wounds and Injuries, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Craniocerebral Trauma, Trauma, Nervous System
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: stem cells<br>autologous bone marrow mononuclear cell transplantation | Biological: Autologous bone marrow mononuclear cell transplantation<br>* bone marrow derived mononuclear cells are administered intrathecally in traumatic brain injury patients<br>|
|
Stem Cell Therapy in Traumatic Brain Injury
Study Overview
=================
Brief Summary
-----------------
The purpose of this study was to study the effect of stem cell therapy on common symptoms in patients with Traumatic Brain Injury
Official Title
-----------------
Open Label Study of Autologous Bone Marrow Mononuclear Cells in Traumatic Brain Injury
Conditions
-----------------
Traumatic Brain Injury
Intervention / Treatment
-----------------
* Biological: Autologous bone marrow mononuclear cell transplantation
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosed cases of chronic traumatic brain injury Age above 6 months Exclusion Criteria: presence of acute infections such as Human immunodeficiency virus/Hepatitis B - Virus/Hepatitis C Virus malignancies bleeding tendencies pneumonia renal failure severe liver dysfunction severe anemia [Hemoglobin < 8] any bone marrow disorder space occupying lesion in brain other acute medical conditions such as respiratory infection and pyrexia pregnancy lactation
Ages Eligible for Study
-----------------
Minimum Age: 6 Months
Maximum Age: 65 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: stem cells<br>autologous bone marrow mononuclear cell transplantation | Biological: Autologous bone marrow mononuclear cell transplantation<br>* bone marrow derived mononuclear cells are administered intrathecally in traumatic brain injury patients<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in clinical symptoms of traumatic brain injury | | 6 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disability Rating scale | | 6 months |
|
||
NCT01728935
|
Tenofovir in Asian Chronic Hepatitis B Patients
|
Tenofovir (TDF) has been demonstrated to have potency antiviral against the hepatitis B virus (HBV) in various multiple-centre trials, with no cases of resistance encountered. However, its efficacy and resistance profile in the Asian population, which constitute the majority of chronic hepatitis B (CHB) patients, is unknown. Compared to other nucleoside analogues, TDF has been associated with relatively high rates of hepatitis B surface antigen (HBsAg) seroclearance. It would be interested to see if this could be reproduced. The investigators plan to report the serologic and virologic results of our 140 nucleoside analogue-experienced patients who were commenced on TDF.
|
Recent multi-center trials have shown tenofovir disoprovil fumarate (TDF) demonstrating potent antiviral efficacy in both nucleoside-naive and -experienced chronic hepatitis B (CHB) patients. At present, there has been no identifiable amino acid substitutions associated with resistance to TDF.~Since TDF and adefovir (ADV), another licensed drug for CHB, belong to same molecular group, acyclic phosphonate, there had been various studies investigating the efficacy of TDF in ADV-resistant patients. The efficacy of tenofovir in this group of patients is conflicting. While several studies have shown TDF achieving similar viral suppression when compared to CHB patients without ADV-resistance , another study found that patients with the signature ADV mutations of rtA181V/T and /or rtN236T responded suboptimally to TDF. For all published studies, the number of patients with documented genotypic resistance to adefovir is actually small (n = 17-40), and therefore, further studies in this area are required.~Another interesting point to note was the relatively high rate of hepatitis B surface antigen (HBsAg) seroclearance found in patients taking TDF. The cumulative rate of HBsAg seroclearance up in hepatitis B e antigen (HBeAg)-positive was 10% after 4 years . However, the same study did not find any HBeAg-negative patients achieving HBsAg seroclearance. In addition, studies on TDF were mainly performed in Caucasian patients, the majority being genotypes A and D. A preliminary study performed in Asian patients, predominantly genotypes B and C, did not discover any cases of HBsAg seroclearance . Given the majority of the CHB population is found in Asia, further studies are needed to clarify if HBsAg seroclearance by nucleoside / nucleotide analogues is potentially achievable using TDF.
|
Serologic and Virologic Outcomes of Tenofovir in Asian Chronic Hepatitis B Patients With Prior Nucleoside Analogue Exposure
|
Chronic Hepatitis B
|
* Drug: Tenofovir disoproxil
|
Inclusion Criteria:~HBsAg-positivity for at least 6 months at presentation~Commenced on tenofovir for chronic hepatitis B~Exposure to other nucleoside analogues before starting TDF~Exclusion Criteria:~Concomitant liver diseases including chronic hepatitis C and/ or D infection, Wilson's disease, autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis.~Significant alcohol intake (> 20 grams per day)
|
18 Years
|
75 Years
|
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum HBV DNA levels | | 3 Years |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resistance Profile | Performed using a Line Probe Assay (LiPA) | 3 Years |
| HBsAg levels | | 3 years |
|
HBV, Tenofovir, HBV DNA, HBsAg, Resistance
|
Anti-Infective Agents, Reverse Transcriptase Inhibitors, Nucleic Acid Synthesis Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action, Anti-HIV Agents, Anti-Retroviral Agents, Tenofovir, Antiviral Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Tenofovir disoproxil<br>Tenofovir disoproxil 300mg daily | Drug: Tenofovir disoproxil<br>* Tenofovir disoproxil 300mg daily<br>* Other names: Viread;|
|
Tenofovir in Asian Chronic Hepatitis B Patients
Study Overview
=================
Brief Summary
-----------------
Tenofovir (TDF) has been demonstrated to have potency antiviral against the hepatitis B virus (HBV) in various multiple-centre trials, with no cases of resistance encountered. However, its efficacy and resistance profile in the Asian population, which constitute the majority of chronic hepatitis B (CHB) patients, is unknown. Compared to other nucleoside analogues, TDF has been associated with relatively high rates of hepatitis B surface antigen (HBsAg) seroclearance. It would be interested to see if this could be reproduced. The investigators plan to report the serologic and virologic results of our 140 nucleoside analogue-experienced patients who were commenced on TDF.
Detailed Description
-----------------
Recent multi-center trials have shown tenofovir disoprovil fumarate (TDF) demonstrating potent antiviral efficacy in both nucleoside-naive and -experienced chronic hepatitis B (CHB) patients. At present, there has been no identifiable amino acid substitutions associated with resistance to TDF. Since TDF and adefovir (ADV), another licensed drug for CHB, belong to same molecular group, acyclic phosphonate, there had been various studies investigating the efficacy of TDF in ADV-resistant patients. The efficacy of tenofovir in this group of patients is conflicting. While several studies have shown TDF achieving similar viral suppression when compared to CHB patients without ADV-resistance , another study found that patients with the signature ADV mutations of rtA181V/T and /or rtN236T responded suboptimally to TDF. For all published studies, the number of patients with documented genotypic resistance to adefovir is actually small (n = 17-40), and therefore, further studies in this area are required. Another interesting point to note was the relatively high rate of hepatitis B surface antigen (HBsAg) seroclearance found in patients taking TDF. The cumulative rate of HBsAg seroclearance up in hepatitis B e antigen (HBeAg)-positive was 10% after 4 years . However, the same study did not find any HBeAg-negative patients achieving HBsAg seroclearance. In addition, studies on TDF were mainly performed in Caucasian patients, the majority being genotypes A and D. A preliminary study performed in Asian patients, predominantly genotypes B and C, did not discover any cases of HBsAg seroclearance . Given the majority of the CHB population is found in Asia, further studies are needed to clarify if HBsAg seroclearance by nucleoside / nucleotide analogues is potentially achievable using TDF.
Official Title
-----------------
Serologic and Virologic Outcomes of Tenofovir in Asian Chronic Hepatitis B Patients With Prior Nucleoside Analogue Exposure
Conditions
-----------------
Chronic Hepatitis B
Intervention / Treatment
-----------------
* Drug: Tenofovir disoproxil
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: HBsAg-positivity for at least 6 months at presentation Commenced on tenofovir for chronic hepatitis B Exposure to other nucleoside analogues before starting TDF Exclusion Criteria: Concomitant liver diseases including chronic hepatitis C and/ or D infection, Wilson's disease, autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis. Significant alcohol intake (> 20 grams per day)
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Tenofovir disoproxil<br>Tenofovir disoproxil 300mg daily | Drug: Tenofovir disoproxil<br>* Tenofovir disoproxil 300mg daily<br>* Other names: Viread;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum HBV DNA levels | | 3 Years |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resistance Profile | Performed using a Line Probe Assay (LiPA) | 3 Years |
| HBsAg levels | | 3 years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HBV, Tenofovir, HBV DNA, HBsAg, Resistance
|
NCT02151500
|
Stress and Health Interview for Primary Care Patients With Medically Unexplained Symptoms
|
The goal of this study is to test the feasibility and acceptability of providing an experiential assessment interview that targets emotional and stressful experiences in primary care. In this randomized, controlled trial, the investigators will compare an interview condition to a wait-list control condition. The investigators hypothesize that helping individuals first identify the links between their stress and symptoms will likely increase their awareness and endorsement of the link between stress and physical symptoms, including a willingness to engage in stress management techniques. It is also expected that helping raise an individual's awareness about their symptoms, followed by an experience and expression of unexpressed emotions is likely to influence their physical symptoms and psychological status.
|
Emotional stress, particularly when a patients inhibits their experiences and feelings, contributes to physical symptoms. However, primary care patients with medically unexplained symptoms are rarely assessed for the stress and emotions in an comprehensive manner. The goal of this study is to test the feasibility and acceptability of providing an experiential assessment interview that targets emotional and stressful experiences in primary care with medically unexplained physical symptoms. In this randomized, controlled trial, the investigators will compare an interview condition to a wait-list control condition. The interview will review patients health history, psychosocial history, make links between the two, and help patients identify and express emotions related to conflicts or victimization. The investigators hypothesize that helping individuals first identify the links between their stress and symptoms will likely increase their awareness and endorsement of the link between stress and physical symptoms, including a willingness to engage in stress management techniques. It is also expected that helping raise an individual's awareness about their symptoms, followed by an experience and expression of unexpressed emotions is likely to influence their physical symptoms and psychological status.
|
Stress and Health Interview for Primary Care Patients With Medically Unexplained Symptoms
|
Somatoform Disorders
|
* Behavioral: Stress and Health Interview
|
Inclusion Criteria:~Participants must score above 10 (moderate range) on the Patient Health Questionnaire-15, which is a measure of a range of medical symptoms that are often medically unexplained.~Exclusion Criteria:~Conditions that could interfere with the interview:~non-English speaking~psychosis~dementia~mental impairment~The presence of disease or injury that could account for the physical symptoms. - Examples: autoimmune disease, bodily injury, serious infection, cancer, heart disease, COPD, post-stroke.
|
18 Years
|
80 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptom Interpretation Questionnaire (SIQ) | | Change from baseline symptom attribution at 6-weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Health Questionnaire-15 (PHQ-15) | | Change from baseline in symptom severity at 6-weeks |
| Brief Pain Inventory (BPI) | | Change from baseline pain at 6-weeks |
| Brief Symptom Inventory (BSI) | | Change from baseline symptoms at 6-weeks |
| Insomnia Severity Scale (ISI) | | Change from baseline insomnia at 6-weeks |
| Brief Fatigue Inventory | | Change from baseline fatigue at 6-weeks |
| Satisfaction with Life Scale (SWLS) | | Change from baseline life satisfaction at 6-weeks |
| Emotional Approach Coping Scale (EAC) | | Change from baseline emotional approach coping at 6-weeks |
| Emotional Processing Scale (EPS) | | Change from baseline emotional processing at 6-weeks |
| Inventory of Interpersonal Problems Scale (IIP-32) | | Change from baseline interpersonal problems at 6-weeks |
| Pain Catastrophizing Scale (PCS) | | Change from baseline pain catastrophizing at 6-weeks |
| Change Assessment Questionnaire | | Changes from baseline stage of change at 6-weeks |
| McGill Pain Questionnaire (SF-MPQ-2) | | Change from baseline pain at 6-weeks |
|
Medically Unexplained Symptoms (MUPS), Somatoform disorders, Chronic pain, Somatic symptoms, Emotional processing, Primary Care
|
Medically Unexplained Symptoms, Somatoform Disorders, Mental Disorders
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stress and Health Interview<br>Stress and Health Interview is an experiential assessment technique | Behavioral: Stress and Health Interview<br>* A stress and health interview which aims to help patients: a) disclose their stressful experiences and emotional conflicts, which might be contributing to their symptoms; b) learn about associations between their stress and physical symptoms; and c) learn about the potential value of experiencing and expressing their emotions related to these stressful situations.<br>|
| No Intervention: Wait-list Control<br>Standard medical care until the 6-week follow-up is completed | |
|
Stress and Health Interview for Primary Care Patients With Medically Unexplained Symptoms
Study Overview
=================
Brief Summary
-----------------
The goal of this study is to test the feasibility and acceptability of providing an experiential assessment interview that targets emotional and stressful experiences in primary care. In this randomized, controlled trial, the investigators will compare an interview condition to a wait-list control condition. The investigators hypothesize that helping individuals first identify the links between their stress and symptoms will likely increase their awareness and endorsement of the link between stress and physical symptoms, including a willingness to engage in stress management techniques. It is also expected that helping raise an individual's awareness about their symptoms, followed by an experience and expression of unexpressed emotions is likely to influence their physical symptoms and psychological status.
Detailed Description
-----------------
Emotional stress, particularly when a patients inhibits their experiences and feelings, contributes to physical symptoms. However, primary care patients with medically unexplained symptoms are rarely assessed for the stress and emotions in an comprehensive manner. The goal of this study is to test the feasibility and acceptability of providing an experiential assessment interview that targets emotional and stressful experiences in primary care with medically unexplained physical symptoms. In this randomized, controlled trial, the investigators will compare an interview condition to a wait-list control condition. The interview will review patients health history, psychosocial history, make links between the two, and help patients identify and express emotions related to conflicts or victimization. The investigators hypothesize that helping individuals first identify the links between their stress and symptoms will likely increase their awareness and endorsement of the link between stress and physical symptoms, including a willingness to engage in stress management techniques. It is also expected that helping raise an individual's awareness about their symptoms, followed by an experience and expression of unexpressed emotions is likely to influence their physical symptoms and psychological status.
Official Title
-----------------
Stress and Health Interview for Primary Care Patients With Medically Unexplained Symptoms
Conditions
-----------------
Somatoform Disorders
Intervention / Treatment
-----------------
* Behavioral: Stress and Health Interview
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants must score above 10 (moderate range) on the Patient Health Questionnaire-15, which is a measure of a range of medical symptoms that are often medically unexplained. Exclusion Criteria: Conditions that could interfere with the interview: non-English speaking psychosis dementia mental impairment The presence of disease or injury that could account for the physical symptoms. - Examples: autoimmune disease, bodily injury, serious infection, cancer, heart disease, COPD, post-stroke.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stress and Health Interview<br>Stress and Health Interview is an experiential assessment technique | Behavioral: Stress and Health Interview<br>* A stress and health interview which aims to help patients: a) disclose their stressful experiences and emotional conflicts, which might be contributing to their symptoms; b) learn about associations between their stress and physical symptoms; and c) learn about the potential value of experiencing and expressing their emotions related to these stressful situations.<br>|
| No Intervention: Wait-list Control<br>Standard medical care until the 6-week follow-up is completed | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptom Interpretation Questionnaire (SIQ) | | Change from baseline symptom attribution at 6-weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Health Questionnaire-15 (PHQ-15) | | Change from baseline in symptom severity at 6-weeks |
| Brief Pain Inventory (BPI) | | Change from baseline pain at 6-weeks |
| Brief Symptom Inventory (BSI) | | Change from baseline symptoms at 6-weeks |
| Insomnia Severity Scale (ISI) | | Change from baseline insomnia at 6-weeks |
| Brief Fatigue Inventory | | Change from baseline fatigue at 6-weeks |
| Satisfaction with Life Scale (SWLS) | | Change from baseline life satisfaction at 6-weeks |
| Emotional Approach Coping Scale (EAC) | | Change from baseline emotional approach coping at 6-weeks |
| Emotional Processing Scale (EPS) | | Change from baseline emotional processing at 6-weeks |
| Inventory of Interpersonal Problems Scale (IIP-32) | | Change from baseline interpersonal problems at 6-weeks |
| Pain Catastrophizing Scale (PCS) | | Change from baseline pain catastrophizing at 6-weeks |
| Change Assessment Questionnaire | | Changes from baseline stage of change at 6-weeks |
| McGill Pain Questionnaire (SF-MPQ-2) | | Change from baseline pain at 6-weeks |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Medically Unexplained Symptoms (MUPS), Somatoform disorders, Chronic pain, Somatic symptoms, Emotional processing, Primary Care
|
NCT05664386
|
Effect of Ciprofol Infusion for Induction and Maintenance on Hemodynamics and Postoperative Recovery
|
To study the Effect of Ciprofol Infusion for Induction and Maintenance of anesthesia on Hemodynamics and Postoperative Recovery in Patients Undergoing Thoracoscopic Lobectomy:a randomized, controlled trial.
|
Patients undergoing Thoracoscopic Lobectomy aged 18~65 years old were randomly assigned to Group P and Group C . Group P was given propofol 2 ~ 2.5mg/kg, group C was given ciprofol 0.4 ~ 0.5mg/kg, if bispectral index(BIS) value ≤60 during anesthesia induction, cisatracurium 0.2mg/kg and sufentanil 0.5μg/kg were injected intravenously, endotracheal intubation was performed after the improvement of muscle relaxation. If the BIS value was greater than 60, propofol was added intravenously 1mg/kg each time or ciprofol 0.2mg/kg each time, and the interval of administration was greater than 1min, until BIS≤60. Cisatracurium and sufentanil were injected intravenously, followed by endotracheal intubation.Then propofol was maintained in group P at 4-12 mg/kg/h and remifentanil was maintained at 0.1-0.3 ug/kg/min .Ciprofol was maintained in Group C at 0.8-2.5 mg/kg/h and remifentanil was maintained at 0.1-0.3 ug/kg/min . Intermittent addition of cisatracurium. Sufentanil was added as required, and total dosage of Sufentanil was 0.7ug ~ 1ug/kg. BIS was kept at 40 ~ 60 during the surgery, and infusion drugs were stopped at the end of the operation. The patients were Transfer to Postanesthesia care unit(PACU) after the operation.~The primary outcomes were the fluctuations in hemodynamic parameters during induction and the surgery. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MAP),heart rate (HR) and BIS values at various time points were collected.~The secondary outcome were as follows:~The time of lose consciousness（LOC） during the induction, The Time and dosage of additional drug, and the BIS value during the induction process.~The incidence of adverse events such as injection pain, body movement, muscle twitching, hypotension, hypertension, bradycardia or tachycardia, cough and bronchospasm during induction.~quality of recovery 15（QOR15） score at pre-operation（Preop） 、on the first day of postoperation （POD1）and on the second day of postoperation （POD2） .~the recovery time of consciousness (ROC）, extubation time, PACU stay time, postoperative hospital stay time.~Incidence of postoperative nausea and vomiting, incidence of postoperative agitation and delayed recovery, and intraoperative awareness.
|
Effect of Ciprofol Infusion for Induction and Maintenance on Hemodynamics and Postoperative Recovery in Patients Undergoing Thoracoscopic Lobectomy : a Randomized, Controlled Trial
|
Hemodynamics, Postoperative Recovery, Anesthesia
|
* Drug: propofol
* Drug: ciprofol
|
Inclusion Criteria:~American Society of Anesthesiology (ASA)Ⅰ～Ⅱ grade;~18-65 years;~Body mass index (BMI) 20-30kg/m2 ;~Scheduled for thoracoscopic lobectomy under general anesthesia;~Exclusion Criteria:~Refused to participate in the clinical study;~Predictable airway difficulties requiring awake intubation;~Allergy to the drugs which were used in this study;~Tracheal intubation failed for twice;~Patients with mental diseases or consciousness disorder;~long-term use of sedatives or Antidepressants;~Patients who are participating in other clinical studies.
|
18 Years
|
65 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemodynamic fluctuations: Systolic blood pressure(SBP) | Systolic blood pressure(SBP) during anesthesia induction and surgery. | during anesthesia induction，perioperative |
| Hemodynamic fluctuations: Diastolic blood pressure(DBP) | Diastolic blood pressure(DBP) during anesthesia induction and surgery. | during anesthesia induction，perioperative |
| Hemodynamic fluctuations: mean blood pressure (MAP) | MAP during anesthesia induction and surgery. | during anesthesia induction，perioperative |
| Hemodynamic fluctuations: Heart rate (HR) | Heart rate (HR) during anesthesia induction and surgery. | during anesthesia induction，perioperative |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The time of lose consciousness（LOC） during the induction | The time of lose consciousness（LOC） during the induction was defined as from the drug was administered until the patients loss of consciousness(when the BIS≤60) | during anesthesia induction |
| The incidence of adverse events during induction | The incidence of adverse events such as injection pain, body movement, muscle twitching, hypotension, hypertension, bradycardia or tachycardia, cough and bronchospasm during induction. | during induction |
| quality of recovery | quality of recovery 15（QOR15） score at pre-operation（Preop） 、 postoperation day 1 ,postoperation of day2 | pre-operation, postoperation of day 1 ,postoperation of day2 |
| postoperative recovery | Incidence of postoperative nausea and vomiting was record use Classification of nausea and vomiting | 2 hours after surgery |
| Incidence of intraoperative awareness | Brice Questionnaire was used to assess the occurrence of intraoperative awareness. | 2 hours after surgery |
|
Postoperative Recovery, Ciprofol, Hemodynamics, propofol
|
Propofol, Hypnotics and Sedatives, Central Nervous System Depressants, Physiological Effects of Drugs, Anesthetics, Intravenous, Anesthetics, General, Anesthetics
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: propofol group<br>According to grouping，patients were premeditated with injection of Propofol 2-2.5mg / kg IV . If BIS is ≤ 60, Tracheal intubation was facilitated with cisatracurium 0.2mg/kg a IV and sufentanil 0.3 μ g / kg IV. if BIS is >60, propofol 1mg/kg was titrated intravenously, with an interval of more than 1min until the BIS is ≤ 60，and intubation was performed after cisatracurium and sufentanil injected .General anesthesia was maintained with Propofol and remifentanil.Then propofol was maintained in group P at 4-12 mg/kg/h and remifentanil was maintained at 0.1-0.3 ug/kg/min .BIS was kept at 40 ~ 60 during the surgery, and infusion drugs were stopped at the end of the operation. The patients were Transfered to Postanesthesia care unit(PACU) after the operation. | Drug: propofol<br>* propofol 2～2.5mg/kg was used for anesthesia induction. propofol is an intravenous sedative-hypnotic and a short-acting GABAA receptor agonist. It activates GABAergic neurons by enhancing chloride ion influx. It is used for anesthesia of induction and maintenance.<br>|
| Experimental: ciprofol group<br>Group C was given ciprofol 0.4 ~ 0.5mg/kg, if bispectral index(BIS) value ≤60 during anesthesia induction, cisatracurium 0.2mg/kg and sufentanil 0.5μg/kg were injected intravenously, endotracheal intubation was performed after the improvement of muscle relaxation. If the BIS value was greater than 60, ciprofol 0.2mg/kg each time, and the interval of administration was greater than 1min, until BIS≤60. Cisatracurium and sufentanil were injected intravenously, followed by endotrachealintubation.Ciprofol was maintained in Group C at 0.8-2.5 mg/kg/h and remifentanil was maintained at 0.1-0.3 ug/kg/min . Intermittent addition of cisatracurium,Sufentanil was added as required, and total dosage of Sufentanil was 0.7ug ~ 1ug/kg. BIS was kept at 40 ~ 60 during the surgery, and infusion drugs were stopped at the end of the operation. The patients were Transfered to Postanesthesia care unit(PACU) after the operation. | Drug: ciprofol<br>* Ciprofol 0.4～0.5mg/kg was used for anesthesia induction. Ciprofol is an intravenous sedative-hypnotic and a short-acting GABAA receptor agonist. It activates GABAergic neurons by enhancing chloride ion influx. It is used for anesthetic induction and maintenance agents include rapid induction of general anesthesia, rapid recovery of consciousness, minimal residual effects on the central nervous system and less injection pain.<br>|
|
Effect of Ciprofol Infusion for Induction and Maintenance on Hemodynamics and Postoperative Recovery
Study Overview
=================
Brief Summary
-----------------
To study the Effect of Ciprofol Infusion for Induction and Maintenance of anesthesia on Hemodynamics and Postoperative Recovery in Patients Undergoing Thoracoscopic Lobectomy:a randomized, controlled trial.
Detailed Description
-----------------
Patients undergoing Thoracoscopic Lobectomy aged 18 65 years old were randomly assigned to Group P and Group C . Group P was given propofol 2 2.5mg/kg, group C was given ciprofol 0.4 0.5mg/kg, if bispectral index(BIS) value ≤60 during anesthesia induction, cisatracurium 0.2mg/kg and sufentanil 0.5μg/kg were injected intravenously, endotracheal intubation was performed after the improvement of muscle relaxation. If the BIS value was greater than 60, propofol was added intravenously 1mg/kg each time or ciprofol 0.2mg/kg each time, and the interval of administration was greater than 1min, until BIS≤60. Cisatracurium and sufentanil were injected intravenously, followed by endotracheal intubation.Then propofol was maintained in group P at 4-12 mg/kg/h and remifentanil was maintained at 0.1-0.3 ug/kg/min .Ciprofol was maintained in Group C at 0.8-2.5 mg/kg/h and remifentanil was maintained at 0.1-0.3 ug/kg/min . Intermittent addition of cisatracurium. Sufentanil was added as required, and total dosage of Sufentanil was 0.7ug 1ug/kg. BIS was kept at 40 60 during the surgery, and infusion drugs were stopped at the end of the operation. The patients were Transfer to Postanesthesia care unit(PACU) after the operation. The primary outcomes were the fluctuations in hemodynamic parameters during induction and the surgery. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MAP),heart rate (HR) and BIS values at various time points were collected. The secondary outcome were as follows: The time of lose consciousness（LOC） during the induction, The Time and dosage of additional drug, and the BIS value during the induction process. The incidence of adverse events such as injection pain, body movement, muscle twitching, hypotension, hypertension, bradycardia or tachycardia, cough and bronchospasm during induction. quality of recovery 15（QOR15） score at pre-operation（Preop） 、on the first day of postoperation （POD1）and on the second day of postoperation （POD2） . the recovery time of consciousness (ROC）, extubation time, PACU stay time, postoperative hospital stay time. Incidence of postoperative nausea and vomiting, incidence of postoperative agitation and delayed recovery, and intraoperative awareness.
Official Title
-----------------
Effect of Ciprofol Infusion for Induction and Maintenance on Hemodynamics and Postoperative Recovery in Patients Undergoing Thoracoscopic Lobectomy : a Randomized, Controlled Trial
Conditions
-----------------
Hemodynamics, Postoperative Recovery, Anesthesia
Intervention / Treatment
-----------------
* Drug: propofol
* Drug: ciprofol
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: American Society of Anesthesiology (ASA)Ⅰ～Ⅱ grade; 18-65 years; Body mass index (BMI) 20-30kg/m2 ; Scheduled for thoracoscopic lobectomy under general anesthesia; Exclusion Criteria: Refused to participate in the clinical study; Predictable airway difficulties requiring awake intubation; Allergy to the drugs which were used in this study; Tracheal intubation failed for twice; Patients with mental diseases or consciousness disorder; long-term use of sedatives or Antidepressants; Patients who are participating in other clinical studies.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: propofol group<br>According to grouping，patients were premeditated with injection of Propofol 2-2.5mg / kg IV . If BIS is ≤ 60, Tracheal intubation was facilitated with cisatracurium 0.2mg/kg a IV and sufentanil 0.3 μ g / kg IV. if BIS is >60, propofol 1mg/kg was titrated intravenously, with an interval of more than 1min until the BIS is ≤ 60，and intubation was performed after cisatracurium and sufentanil injected .General anesthesia was maintained with Propofol and remifentanil.Then propofol was maintained in group P at 4-12 mg/kg/h and remifentanil was maintained at 0.1-0.3 ug/kg/min .BIS was kept at 40 60 during the surgery, and infusion drugs were stopped at the end of the operation. The patients were Transfered to Postanesthesia care unit(PACU) after the operation. | Drug: propofol<br>* propofol 2～2.5mg/kg was used for anesthesia induction. propofol is an intravenous sedative-hypnotic and a short-acting GABAA receptor agonist. It activates GABAergic neurons by enhancing chloride ion influx. It is used for anesthesia of induction and maintenance.<br>|
| Experimental: ciprofol group<br>Group C was given ciprofol 0.4 0.5mg/kg, if bispectral index(BIS) value ≤60 during anesthesia induction, cisatracurium 0.2mg/kg and sufentanil 0.5μg/kg were injected intravenously, endotracheal intubation was performed after the improvement of muscle relaxation. If the BIS value was greater than 60, ciprofol 0.2mg/kg each time, and the interval of administration was greater than 1min, until BIS≤60. Cisatracurium and sufentanil were injected intravenously, followed by endotrachealintubation.Ciprofol was maintained in Group C at 0.8-2.5 mg/kg/h and remifentanil was maintained at 0.1-0.3 ug/kg/min . Intermittent addition of cisatracurium,Sufentanil was added as required, and total dosage of Sufentanil was 0.7ug 1ug/kg. BIS was kept at 40 60 during the surgery, and infusion drugs were stopped at the end of the operation. The patients were Transfered to Postanesthesia care unit(PACU) after the operation. | Drug: ciprofol<br>* Ciprofol 0.4～0.5mg/kg was used for anesthesia induction. Ciprofol is an intravenous sedative-hypnotic and a short-acting GABAA receptor agonist. It activates GABAergic neurons by enhancing chloride ion influx. It is used for anesthetic induction and maintenance agents include rapid induction of general anesthesia, rapid recovery of consciousness, minimal residual effects on the central nervous system and less injection pain.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemodynamic fluctuations: Systolic blood pressure(SBP) | Systolic blood pressure(SBP) during anesthesia induction and surgery. | during anesthesia induction，perioperative |
| Hemodynamic fluctuations: Diastolic blood pressure(DBP) | Diastolic blood pressure(DBP) during anesthesia induction and surgery. | during anesthesia induction，perioperative |
| Hemodynamic fluctuations: mean blood pressure (MAP) | MAP during anesthesia induction and surgery. | during anesthesia induction，perioperative |
| Hemodynamic fluctuations: Heart rate (HR) | Heart rate (HR) during anesthesia induction and surgery. | during anesthesia induction，perioperative |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The time of lose consciousness（LOC） during the induction | The time of lose consciousness（LOC） during the induction was defined as from the drug was administered until the patients loss of consciousness(when the BIS≤60) | during anesthesia induction |
| The incidence of adverse events during induction | The incidence of adverse events such as injection pain, body movement, muscle twitching, hypotension, hypertension, bradycardia or tachycardia, cough and bronchospasm during induction. | during induction |
| quality of recovery | quality of recovery 15（QOR15） score at pre-operation（Preop） 、 postoperation day 1 ,postoperation of day2 | pre-operation, postoperation of day 1 ,postoperation of day2 |
| postoperative recovery | Incidence of postoperative nausea and vomiting was record use Classification of nausea and vomiting | 2 hours after surgery |
| Incidence of intraoperative awareness | Brice Questionnaire was used to assess the occurrence of intraoperative awareness. | 2 hours after surgery |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Postoperative Recovery, Ciprofol, Hemodynamics, propofol
|
NCT04546360
|
Spleen Stiffness Combined With Liver Stiffness Measured by 2D-SWE for the Screening of High-risk Varices in Compensated Advanced Chronic Liver Disease (CHESS2004)
|
Variceal hemorrhage is the serious complication in patients with compensated advanced chronic liver disease (cACLD). To evaluate the bleeding risk of varices, esophagogastroduodenoscopy (EGD) should be performed. However, EGD is limited by its invasiveness and uncomfortableness. The Baveno VI criteria recommended that EGD could be spared in patients with liver stiffness (LS) based on transient elastography (TE) < 20 kPa and platelet count >150000/mm3. However, only 30% of patients can spare EGD. In order to expand the screening criteria, Expanded-Baveno VI proposed that by using LS (TE)<25 kPa and platelet count >110000/mm3, 40% of patients can safely avoid EGD. It is worth noting that the Baveno VI criteria is based on the European and American compensatory cirrhosis cohort (55% for hepatitis C, 14% for non-alcoholic steatohepatitis, 13% for alcoholic hepatitis, 8% for hepatitis B), Expanded-Baveno VI is also of good diagnostic value for hepatitis C, alcoholic, and non-alcoholic steatohepatitis of cACLD. About 257 million people worldwide are infected with hepatitis B virus, and about 80 million people in China alone are infected with hepatitis B virus. Infected with hepatitis B virus is the main etiology of patients with cACLD in china. Hence, Baveno VI and Expanded-Baveno VI may not be suitable for patients with hepatitis B virus-dominant cACLD.~Previous studies have shown that LS has a significant correlation with the severity of portal hypertension. Nevertheless, LS only has a good correlation with portal pressure in the early stage of portal hypertension (hepatic vein pressure gradient ≤10mm Hg), because liver fibrosis is the main cause of portal hypertension in this period. In the late stage of liver cirrhosis, the involvement of hyperdynamic circulation and increased portal blood flow, spleen stiffness (SS) may have a better correlation with HVPG than that of LS. Therefore, SS provides a reliable basis for the hemodynamic changes that occur during the development of liver cirrhosis and avoids the limitations caused by the measurement of LS. Previous study has found that changes in SS before and after non-selective beta-blockers (NSBBs) as primary prophylaxis may be a promising non-invasive tool for predicting hemodynamic response in patients with high-risk varices.~Since SS is much higher than LS, the maximum threshold of 75 kPa measured with TE may not be sufficient to evaluate the hardness of the spleen. Meanwhile, numerous studies have found that the success rate of measuring SS and LS based on 2D-SWE is higher than that of TE. Hence, CHESS2004 study aims to establish a standard for predicting high-risk varices that is more suitable in patients with hepatitis B virus-dominant cACLD. In addition, non-invasive means of SS is used to evaluate the hemodynamic response of patients with high-risk varices receiving prophylaxis NSBBs therapy.
|
Variceal hemorrhage is the serious complication in patients with compensated advanced chronic liver disease (cACLD). To evaluate the bleeding risk of varices, esophagogastroduodenoscopy (EGD) should be performed. However, EGD is limited by its invasiveness and uncomfortableness. The Baveno VI criteria recommended that EGD could be spared in patients with liver stiffness (LS) based on transient elastography (TE) < 20 kPa and platelet count >150000/mm3. However, only 30% of patients can spare EGD. In order to expand the screening criteria, Expanded-Baveno VI proposed that by using LS (TE)<25 kPa and platelet count >110000/mm3, 40% of patients can safely avoid EGD. It is worth noting that the Baveno VI criteria is based on the European and American compensatory cirrhosis cohort (55% for hepatitis C, 14% for non-alcoholic steatohepatitis, 13% for alcoholic hepatitis, 8% for hepatitis B), Expanded-Baveno VI is also of good diagnostic value for hepatitis C, alcoholic, and non-alcoholic steatohepatitis of cACLD. About 257 million people worldwide are infected with hepatitis B virus, and about 80 million people in China alone are infected with hepatitis B virus. Infected with hepatitis B virus is the main etiology of patients with cACLD in china. Hence, Baveno VI and Expanded-Baveno VI may not be suitable for patients with hepatitis B virus-dominant cACLD.~Previous studies have shown that LS has a significant correlation with the severity of portal hypertension. Nevertheless, LS only has a good correlation with portal pressure in the early stage of portal hypertension (hepatic vein pressure gradient ≤10mm Hg), because liver fibrosis is the main cause of portal hypertension in this period. In the late stage of liver cirrhosis, the involvement of hyperdynamic circulation and increased portal blood flow, spleen stiffness (SS) may have a better correlation with HVPG than that of LS. Therefore, SS provides a reliable basis for the hemodynamic changes that occur during the development of liver cirrhosis and avoids the limitations caused by the measurement of LS. Previous study has found that changes in SS before and after non-selective beta-blockers (NSBBs) as primary prophylaxis may be a promising non-invasive tool for predicting hemodynamic response in patients with high-risk varices.~Since SS is much higher than LS, the maximum threshold of 75 kPa measured with TE may not be sufficient to evaluate the hardness of the spleen. Numerous studies have found that the success rate of measuring SS and LS based on two-dimensional shear wave elastography is higher than that of TE. Hence, CHESS2004 study in seven centers including LanZhou University, Tianjin Second People's Hospital, Sixth People's Hospital of Shenyang, Hospital of the Chengdu Office of the People's Government of Tibet Autonomous Region, The Central Hospital of Lishui City and Guangxi Zhuang Autonomous Region, aims to establish a standard for predicting high-risk varices that is more suitable in patients with hepatitis B virus-dominant cACLD. In addition, non-invasive means of SS is used to evaluate the hemodynamic response of patients with high-risk varices receiving prophylaxis NSBBs therapy.
|
Spleen Stiffness Combined With Liver Stiffness Measured by Two-dimensional Shear Wave Elastography for the Screening of High-risk Varices in Patients With Compensated Advanced Chronic Liver Disease (CHESS2004)
|
Compensated Advanced Chronic Liver Disease, Variceal Hemorrhage
|
* Procedure: Esophagogasrtoduodendoscopy, spleen stiffness measurement and liver stiffness measurement.
|
Inclusion Criteria:~age 18-75 years;~confirmed cirrhosis based on liver biopsy or clinical findings;~without decompensated events (e.g. ascites, bleeding, or overt encephalopathy);~scheduled to undergo esophagogastroduodenoscopy, spleen stiffness measurement and liver stiffness measurement;~estimated survival time>24 months, and model for end-stage liver disease score<19, and without liver transplant;~with written informed consent.~Exclusion Criteria:~contradictions for esophagogastroduodenoscopy;~accepted primary prevention (non-selective beta blockers or endoscopic variceal ligation);~time frame between elastography measurement and esophagogastroduodenoscopy>14 days;~diagnosed as hepatocellular carcinoma;~absence of spleen or splenectomy.
|
18 Years
|
75 Years
|
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Accuracy of combined model of spleen stiffness and liver stiffness | To assess the accuracy of combined model of spleen stiffness and liver stiffness to avoid unnecessary esophagogasrtoduodendoscopy in patients with compensated advanced chronic liver disease | 1 day |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Accuracy of LSPS model base on two-dimensional shear wave elastography | To assess the accuracy of LSPS (liver stiffness-spleen size- to platelet ration risk score) base on two-dimensional shear wave elastography for high-risk varices in patients with compensated advanced chronic liver disease | 1 day |
| Rate of hemodynamic responder of patients receiving prophylaxis NSBBs therapy | Rate of hemodynamic responder of patients receiving prophylaxis NSBBs therapy assessed by spleen stiffness | 1 month |
|
Spleen stiffness, Liver stiffness, Two-dimensional shear wave elastography, High-risk varices
|
Liver Diseases, Hemorrhage, Pathologic Processes, Digestive System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Overall eligible participants<br>Eligible participants will receive standard esophagogasrtoduodendoscopy, spleen stiffness measurement and liver stiffness measurement based on two-dimensional shear wave elastography, gallbladder wall thickness, spleen thickness, spleen long diameter and serological examination (platelet count, alanine aminotransferase, aspartate aminotransferase, total bilirubin, creatinine, albumin, prothrombin time, international normalized ratio). | Procedure: Esophagogasrtoduodendoscopy, spleen stiffness measurement and liver stiffness measurement.<br>* Time frame between elastography measurement and esophagogastroduodendoscopy is within 2 weeks.<br>|
|
Spleen Stiffness Combined With Liver Stiffness Measured by 2D-SWE for the Screening of High-risk Varices in Compensated Advanced Chronic Liver Disease (CHESS2004)
Study Overview
=================
Brief Summary
-----------------
Variceal hemorrhage is the serious complication in patients with compensated advanced chronic liver disease (cACLD). To evaluate the bleeding risk of varices, esophagogastroduodenoscopy (EGD) should be performed. However, EGD is limited by its invasiveness and uncomfortableness. The Baveno VI criteria recommended that EGD could be spared in patients with liver stiffness (LS) based on transient elastography (TE) < 20 kPa and platelet count >150000/mm3. However, only 30% of patients can spare EGD. In order to expand the screening criteria, Expanded-Baveno VI proposed that by using LS (TE)<25 kPa and platelet count >110000/mm3, 40% of patients can safely avoid EGD. It is worth noting that the Baveno VI criteria is based on the European and American compensatory cirrhosis cohort (55% for hepatitis C, 14% for non-alcoholic steatohepatitis, 13% for alcoholic hepatitis, 8% for hepatitis B), Expanded-Baveno VI is also of good diagnostic value for hepatitis C, alcoholic, and non-alcoholic steatohepatitis of cACLD. About 257 million people worldwide are infected with hepatitis B virus, and about 80 million people in China alone are infected with hepatitis B virus. Infected with hepatitis B virus is the main etiology of patients with cACLD in china. Hence, Baveno VI and Expanded-Baveno VI may not be suitable for patients with hepatitis B virus-dominant cACLD. Previous studies have shown that LS has a significant correlation with the severity of portal hypertension. Nevertheless, LS only has a good correlation with portal pressure in the early stage of portal hypertension (hepatic vein pressure gradient ≤10mm Hg), because liver fibrosis is the main cause of portal hypertension in this period. In the late stage of liver cirrhosis, the involvement of hyperdynamic circulation and increased portal blood flow, spleen stiffness (SS) may have a better correlation with HVPG than that of LS. Therefore, SS provides a reliable basis for the hemodynamic changes that occur during the development of liver cirrhosis and avoids the limitations caused by the measurement of LS. Previous study has found that changes in SS before and after non-selective beta-blockers (NSBBs) as primary prophylaxis may be a promising non-invasive tool for predicting hemodynamic response in patients with high-risk varices. Since SS is much higher than LS, the maximum threshold of 75 kPa measured with TE may not be sufficient to evaluate the hardness of the spleen. Meanwhile, numerous studies have found that the success rate of measuring SS and LS based on 2D-SWE is higher than that of TE. Hence, CHESS2004 study aims to establish a standard for predicting high-risk varices that is more suitable in patients with hepatitis B virus-dominant cACLD. In addition, non-invasive means of SS is used to evaluate the hemodynamic response of patients with high-risk varices receiving prophylaxis NSBBs therapy.
Detailed Description
-----------------
Variceal hemorrhage is the serious complication in patients with compensated advanced chronic liver disease (cACLD). To evaluate the bleeding risk of varices, esophagogastroduodenoscopy (EGD) should be performed. However, EGD is limited by its invasiveness and uncomfortableness. The Baveno VI criteria recommended that EGD could be spared in patients with liver stiffness (LS) based on transient elastography (TE) < 20 kPa and platelet count >150000/mm3. However, only 30% of patients can spare EGD. In order to expand the screening criteria, Expanded-Baveno VI proposed that by using LS (TE)<25 kPa and platelet count >110000/mm3, 40% of patients can safely avoid EGD. It is worth noting that the Baveno VI criteria is based on the European and American compensatory cirrhosis cohort (55% for hepatitis C, 14% for non-alcoholic steatohepatitis, 13% for alcoholic hepatitis, 8% for hepatitis B), Expanded-Baveno VI is also of good diagnostic value for hepatitis C, alcoholic, and non-alcoholic steatohepatitis of cACLD. About 257 million people worldwide are infected with hepatitis B virus, and about 80 million people in China alone are infected with hepatitis B virus. Infected with hepatitis B virus is the main etiology of patients with cACLD in china. Hence, Baveno VI and Expanded-Baveno VI may not be suitable for patients with hepatitis B virus-dominant cACLD. Previous studies have shown that LS has a significant correlation with the severity of portal hypertension. Nevertheless, LS only has a good correlation with portal pressure in the early stage of portal hypertension (hepatic vein pressure gradient ≤10mm Hg), because liver fibrosis is the main cause of portal hypertension in this period. In the late stage of liver cirrhosis, the involvement of hyperdynamic circulation and increased portal blood flow, spleen stiffness (SS) may have a better correlation with HVPG than that of LS. Therefore, SS provides a reliable basis for the hemodynamic changes that occur during the development of liver cirrhosis and avoids the limitations caused by the measurement of LS. Previous study has found that changes in SS before and after non-selective beta-blockers (NSBBs) as primary prophylaxis may be a promising non-invasive tool for predicting hemodynamic response in patients with high-risk varices. Since SS is much higher than LS, the maximum threshold of 75 kPa measured with TE may not be sufficient to evaluate the hardness of the spleen. Numerous studies have found that the success rate of measuring SS and LS based on two-dimensional shear wave elastography is higher than that of TE. Hence, CHESS2004 study in seven centers including LanZhou University, Tianjin Second People's Hospital, Sixth People's Hospital of Shenyang, Hospital of the Chengdu Office of the People's Government of Tibet Autonomous Region, The Central Hospital of Lishui City and Guangxi Zhuang Autonomous Region, aims to establish a standard for predicting high-risk varices that is more suitable in patients with hepatitis B virus-dominant cACLD. In addition, non-invasive means of SS is used to evaluate the hemodynamic response of patients with high-risk varices receiving prophylaxis NSBBs therapy.
Official Title
-----------------
Spleen Stiffness Combined With Liver Stiffness Measured by Two-dimensional Shear Wave Elastography for the Screening of High-risk Varices in Patients With Compensated Advanced Chronic Liver Disease (CHESS2004)
Conditions
-----------------
Compensated Advanced Chronic Liver Disease, Variceal Hemorrhage
Intervention / Treatment
-----------------
* Procedure: Esophagogasrtoduodendoscopy, spleen stiffness measurement and liver stiffness measurement.
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: age 18-75 years; confirmed cirrhosis based on liver biopsy or clinical findings; without decompensated events (e.g. ascites, bleeding, or overt encephalopathy); scheduled to undergo esophagogastroduodenoscopy, spleen stiffness measurement and liver stiffness measurement; estimated survival time>24 months, and model for end-stage liver disease score<19, and without liver transplant; with written informed consent. Exclusion Criteria: contradictions for esophagogastroduodenoscopy; accepted primary prevention (non-selective beta blockers or endoscopic variceal ligation); time frame between elastography measurement and esophagogastroduodenoscopy>14 days; diagnosed as hepatocellular carcinoma; absence of spleen or splenectomy.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Overall eligible participants<br>Eligible participants will receive standard esophagogasrtoduodendoscopy, spleen stiffness measurement and liver stiffness measurement based on two-dimensional shear wave elastography, gallbladder wall thickness, spleen thickness, spleen long diameter and serological examination (platelet count, alanine aminotransferase, aspartate aminotransferase, total bilirubin, creatinine, albumin, prothrombin time, international normalized ratio). | Procedure: Esophagogasrtoduodendoscopy, spleen stiffness measurement and liver stiffness measurement.<br>* Time frame between elastography measurement and esophagogastroduodendoscopy is within 2 weeks.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Accuracy of combined model of spleen stiffness and liver stiffness | To assess the accuracy of combined model of spleen stiffness and liver stiffness to avoid unnecessary esophagogasrtoduodendoscopy in patients with compensated advanced chronic liver disease | 1 day |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Accuracy of LSPS model base on two-dimensional shear wave elastography | To assess the accuracy of LSPS (liver stiffness-spleen size- to platelet ration risk score) base on two-dimensional shear wave elastography for high-risk varices in patients with compensated advanced chronic liver disease | 1 day |
| Rate of hemodynamic responder of patients receiving prophylaxis NSBBs therapy | Rate of hemodynamic responder of patients receiving prophylaxis NSBBs therapy assessed by spleen stiffness | 1 month |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Spleen stiffness, Liver stiffness, Two-dimensional shear wave elastography, High-risk varices
|
|
NCT02205450
|
Growth Hormone in Children Under 2 Years With Prader-Willi in Hospital of Sabadell
|
The PWS is a genetic disease with intellectual disabilities associated with multiple manifestations in other body systems. It is characterized by hypothalamic-pituitary abnormalities with severe hypotonia during the early years of life, conditioning feeding difficulties. Hyperphagia appears later, causing severe obesity in pre - school ages. Other endocrine abnormalities associated produce short stature, GH deficiency and hypogonadotropic hypogonadism. These patients also have varying cognitive dysfunction associated as well as learning problems, compounded by the development of psychological-psychiatric and behavioral problems language. The aetiology of GH decreased secretion of the SPW is controversial, it is known that IGF -1 levels are reduced in children and adults with PWS. The rational use of GH is derived from knowledge of comorbidities observed in PWS, which seem to be related to GH deficiency: hypotonia, altered body composition, decreased growth, even obesity.~• The GH is accepted since 2000 for the treatment of PWS. Following fatal episodes in our country, it was decided to start treatment at 2 years of age in an arbitrary manner, but not in the U.S. or France. Subsequent studies have found that GH per se is not a risk factor for mortality. The currently published data supporting the benefits of GH treatment when started between 4 and 6 months of life, even some experts advocate starting at 3 months, but due to the lack of consensus on the age of onset treatment, despite the benefits of your home at an early age before the onset of obesity often starts around 2 years of life.~HYPOTHESIS The use of GH is safe and effective in patients with PWS children under 2 years old.
|
Experience With Growth Hormone (GH) in Children Under 2 Years With Prader-Willi Syndrome (PWS) in the Pediatric Endocrine Department of the Hospital of Sabadell
|
Prader-Willi Syndrome
|
* Drug: Recombinant Somatropin
|
Inclusion Criteria:~Children under 2 years~Exclusion Criteria:~-
|
3 Months
|
2 Years
|
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the safe use of GH in children under 2 year old with Prader Willi Syndrome | Collect any Serious Adverse Event during the length of study | Two years |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the impact of treatment with GH in kids under 2 years old on body composition | | Every 3 months during 2 years |
| Evaluate the impact of treatment with GH in kids under 2 years old on start walking | | Every 3 months during 2 years |
| Evaluate the impact of treatment with GH in kids under 2 years old on the speech beginning | | Every 3 months during 2 years |
|
Prader-Willi Syndrome, Growth Hormone, Children
|
Prader-Willi Syndrome, Syndrome, Disease, Pathologic Processes, Intellectual Disability, Neurobehavioral Manifestations, Neurologic Manifestations, Nervous System Diseases, Abnormalities, Multiple, Congenital Abnormalities, Chromosome Disorders, Genetic Diseases, Inborn, Obesity, Overweight, Overnutrition, Nutrition Disorders
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Children under 2 years with Prader-Willi Syndrome<br> | Drug: Recombinant Somatropin<br> <br> |
|
Growth Hormone in Children Under 2 Years With Prader-Willi in Hospital of Sabadell
Study Overview
=================
Brief Summary
-----------------
The PWS is a genetic disease with intellectual disabilities associated with multiple manifestations in other body systems. It is characterized by hypothalamic-pituitary abnormalities with severe hypotonia during the early years of life, conditioning feeding difficulties. Hyperphagia appears later, causing severe obesity in pre - school ages. Other endocrine abnormalities associated produce short stature, GH deficiency and hypogonadotropic hypogonadism. These patients also have varying cognitive dysfunction associated as well as learning problems, compounded by the development of psychological-psychiatric and behavioral problems language. The aetiology of GH decreased secretion of the SPW is controversial, it is known that IGF -1 levels are reduced in children and adults with PWS. The rational use of GH is derived from knowledge of comorbidities observed in PWS, which seem to be related to GH deficiency: hypotonia, altered body composition, decreased growth, even obesity. • The GH is accepted since 2000 for the treatment of PWS. Following fatal episodes in our country, it was decided to start treatment at 2 years of age in an arbitrary manner, but not in the U.S. or France. Subsequent studies have found that GH per se is not a risk factor for mortality. The currently published data supporting the benefits of GH treatment when started between 4 and 6 months of life, even some experts advocate starting at 3 months, but due to the lack of consensus on the age of onset treatment, despite the benefits of your home at an early age before the onset of obesity often starts around 2 years of life. HYPOTHESIS The use of GH is safe and effective in patients with PWS children under 2 years old.
Official Title
-----------------
Experience With Growth Hormone (GH) in Children Under 2 Years With Prader-Willi Syndrome (PWS) in the Pediatric Endocrine Department of the Hospital of Sabadell
Conditions
-----------------
Prader-Willi Syndrome
Intervention / Treatment
-----------------
* Drug: Recombinant Somatropin
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Children under 2 years Exclusion Criteria: -
Ages Eligible for Study
-----------------
Minimum Age: 3 Months
Maximum Age: 2 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Children under 2 years with Prader-Willi Syndrome<br> | Drug: Recombinant Somatropin<br> <br> |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the safe use of GH in children under 2 year old with Prader Willi Syndrome | Collect any Serious Adverse Event during the length of study | Two years |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the impact of treatment with GH in kids under 2 years old on body composition | | Every 3 months during 2 years |
| Evaluate the impact of treatment with GH in kids under 2 years old on start walking | | Every 3 months during 2 years |
| Evaluate the impact of treatment with GH in kids under 2 years old on the speech beginning | | Every 3 months during 2 years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Prader-Willi Syndrome, Growth Hormone, Children
|
||
NCT04914676
|
Accelerated Dose Schedule of Cytarabine Consolidation Therapy for Older Patients With Acute Myeloid Leukemia (AML) in Complete Remission
|
This phase 2, open label, non-randomized study will evaluate the safety of administering high dose cytarabine (HiDAC) consolidation therapy on days 1-3 of each cycle, as compared to standard administration on days 1, 3, and 5 of each cycle, in patients 61 years and older with de novo acute myeloid leukemia (AML).
|
Accelerated Dose Schedule of Cytarabine Consolidation Therapy for Patients With Acute Myeloid Leukemia (AML) in Complete Remission
|
Acute Myeloid Leukemia
|
* Drug: Cytarabine
* Drug: Cytarabine
|
Inclusion Criteria:~Both males and females ≥ 61 years of age~A clinical diagnosis of de novo, non-M3 acute myeloid leukemia (AML) confirmed by greater than 20% blasts in peripheral blood or on diagnostic bone marrow biopsy who have completed intensive induction chemotherapy and are confirmed in complete remission #1 (defined by < 5% myeloblasts on recovery bone marrow biopsy, Absolute neutrophil count > 1000/uL and platelets > 100x103/uL) and able to receive HiDAC consolidation #1~Patients on the prospective arm must be willing to have labs/clinic visits at UF Health Shands approximately every 48 hours +/- 24 hours after discharge from chemotherapy admission to be included. If prospective subjects cannot be followed at the UF site then telephone visits are allowed to follow for toxicity and transfusions. Records can be requested from subject's local physician office.~Written informed consent obtained from the subject and the subject agrees to comply with all the study-related procedures. For subjects on the historical arm, there will be a waiver of informed consent (as these patients may be deceased or not be available for retrospective consent).~Exclusion Criteria:~Age < 61 years~Patients unable to provide informed consent for prospective arm~Secondary AML (documented history of antecedent hematological disorder, such as myelodysplastic syndrome or therapy-related AML) or chronic myeloid leukemia (CML) in blast crisis~Patients receiving, received, or who will receive a FLT3 inhibitor~Patients receiving, received, or who will receive an IDH1 or IDH2 inhibitor~Serum creatinine greater than 2 mg/dL~History of any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of protocol therapy or that might affect the interpretation of the results of the study or that puts the subject at high risk for treatment complications, in the opinion of the treating physician~Prisoners or subjects who are involuntarily incarcerated, or subjects who are compulsorily detained for treatment of either a psychiatric or physical illness~For historical arm, subjects will be excluded if adequate data is not available in electronic medical record (e.g., if patient was followed by their local oncologist between chemotherapy cycles and labs/transfusions/clinic notes, etc. are not available)~Karnofsky performance status of 40 or less at study entry
|
61 Years
|
99 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of neutropenia | Determine the duration of neutropenia in older patients with de novo AML after consolidation chemotherapy with HiDAC 123, as compared to historical controls treated with HiDAC 135. | 5 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of thrombocytopenia | Determine the duration of thrombocytopenia in older patients with de novo AML after consolidation chemotherapy with HiDAC 123, as compared to historical controls treated with HiDAC 135. | 5 months |
| Incidence of documented infections | Compare the incidence of documented infections (bloodstream infection, pneumonia, invasive fungal infection, Clostridium difficile infection, typhlitis, and febrile neutropenia) in patients receiving HiDAC 123 and HiDAC 135. | 5 months |
| Number of transfusions | Compare the number of red blood cell and platelet transfusions per cycle in patients receiving HiDAC 123 and HiDAC 135. | 4 months |
| Readmission rates and length of readmission stay | Compare the incidence of readmission and the length of readmission stay in patients receiving HiDAC 123 and HiDAC 135. | 5 months |
| Non-hematologic toxicities | Compare the differences in non-hematologic toxicities in patients receiving HiDAC 123 and HiDAC 135. | 5 months |
| Time to next treatment | Compare the time to next treatment (next chemotherapy cycle, transplant, etc.) in patients receiving HiDAC 123 and HiDAC 135. | 5 months |
|
bone marrow, acute myeloid leukemia, high dose cytarabine, HiDAC, consolidation, chemotherapy schedule, elderly
|
Cytarabine, Antimetabolites, Antineoplastic, Antimetabolites, Molecular Mechanisms of Pharmacological Action, Antineoplastic Agents, Antiviral Agents, Anti-Infective Agents, Immunosuppressive Agents, Immunologic Factors, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prospective HiDAC Treatment (HiDAC 123)<br>Subject on this arm will be treated with HiDAC prospectively. | Drug: Cytarabine<br>* Subjects on this arm will prospectively receive consolidation therapy with cytarabine. Subjects will be treated with 1000 mg/m2 cytarabine intravenously every 12 hours on Days 1-3 of each consolidation cycle. Subjects will receive up to four consolidation cycles.<br>* Other names: Ara-C;|
| Other: Historical HiDAC Treatment (HiDAC 135)<br>Subjects on this arm will be historical controls who have previously received treatment with HiDAC. | Drug: Cytarabine<br>* Subjects on this arm will have received consolidation therapy with cytarabine between 2/1/2017 and 2/1/2019. Subjects will have received 1000 mg/m2 cytarabine intravenously every 12 hours on days 1, 3, and 5 of each consolidation cycle and will have received up to 4 consolidation cycles.<br>* Other names: Ara-C;|
|
Accelerated Dose Schedule of Cytarabine Consolidation Therapy for Older Patients With Acute Myeloid Leukemia (AML) in Complete Remission
Study Overview
=================
Brief Summary
-----------------
This phase 2, open label, non-randomized study will evaluate the safety of administering high dose cytarabine (HiDAC) consolidation therapy on days 1-3 of each cycle, as compared to standard administration on days 1, 3, and 5 of each cycle, in patients 61 years and older with de novo acute myeloid leukemia (AML).
Official Title
-----------------
Accelerated Dose Schedule of Cytarabine Consolidation Therapy for Patients With Acute Myeloid Leukemia (AML) in Complete Remission
Conditions
-----------------
Acute Myeloid Leukemia
Intervention / Treatment
-----------------
* Drug: Cytarabine
* Drug: Cytarabine
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Both males and females ≥ 61 years of age A clinical diagnosis of de novo, non-M3 acute myeloid leukemia (AML) confirmed by greater than 20% blasts in peripheral blood or on diagnostic bone marrow biopsy who have completed intensive induction chemotherapy and are confirmed in complete remission #1 (defined by < 5% myeloblasts on recovery bone marrow biopsy, Absolute neutrophil count > 1000/uL and platelets > 100x103/uL) and able to receive HiDAC consolidation #1 Patients on the prospective arm must be willing to have labs/clinic visits at UF Health Shands approximately every 48 hours +/- 24 hours after discharge from chemotherapy admission to be included. If prospective subjects cannot be followed at the UF site then telephone visits are allowed to follow for toxicity and transfusions. Records can be requested from subject's local physician office. Written informed consent obtained from the subject and the subject agrees to comply with all the study-related procedures. For subjects on the historical arm, there will be a waiver of informed consent (as these patients may be deceased or not be available for retrospective consent). Exclusion Criteria: Age < 61 years Patients unable to provide informed consent for prospective arm Secondary AML (documented history of antecedent hematological disorder, such as myelodysplastic syndrome or therapy-related AML) or chronic myeloid leukemia (CML) in blast crisis Patients receiving, received, or who will receive a FLT3 inhibitor Patients receiving, received, or who will receive an IDH1 or IDH2 inhibitor Serum creatinine greater than 2 mg/dL History of any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of protocol therapy or that might affect the interpretation of the results of the study or that puts the subject at high risk for treatment complications, in the opinion of the treating physician Prisoners or subjects who are involuntarily incarcerated, or subjects who are compulsorily detained for treatment of either a psychiatric or physical illness For historical arm, subjects will be excluded if adequate data is not available in electronic medical record (e.g., if patient was followed by their local oncologist between chemotherapy cycles and labs/transfusions/clinic notes, etc. are not available) Karnofsky performance status of 40 or less at study entry
Ages Eligible for Study
-----------------
Minimum Age: 61 Years
Maximum Age: 99 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prospective HiDAC Treatment (HiDAC 123)<br>Subject on this arm will be treated with HiDAC prospectively. | Drug: Cytarabine<br>* Subjects on this arm will prospectively receive consolidation therapy with cytarabine. Subjects will be treated with 1000 mg/m2 cytarabine intravenously every 12 hours on Days 1-3 of each consolidation cycle. Subjects will receive up to four consolidation cycles.<br>* Other names: Ara-C;|
| Other: Historical HiDAC Treatment (HiDAC 135)<br>Subjects on this arm will be historical controls who have previously received treatment with HiDAC. | Drug: Cytarabine<br>* Subjects on this arm will have received consolidation therapy with cytarabine between 2/1/2017 and 2/1/2019. Subjects will have received 1000 mg/m2 cytarabine intravenously every 12 hours on days 1, 3, and 5 of each consolidation cycle and will have received up to 4 consolidation cycles.<br>* Other names: Ara-C;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of neutropenia | Determine the duration of neutropenia in older patients with de novo AML after consolidation chemotherapy with HiDAC 123, as compared to historical controls treated with HiDAC 135. | 5 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of thrombocytopenia | Determine the duration of thrombocytopenia in older patients with de novo AML after consolidation chemotherapy with HiDAC 123, as compared to historical controls treated with HiDAC 135. | 5 months |
| Incidence of documented infections | Compare the incidence of documented infections (bloodstream infection, pneumonia, invasive fungal infection, Clostridium difficile infection, typhlitis, and febrile neutropenia) in patients receiving HiDAC 123 and HiDAC 135. | 5 months |
| Number of transfusions | Compare the number of red blood cell and platelet transfusions per cycle in patients receiving HiDAC 123 and HiDAC 135. | 4 months |
| Readmission rates and length of readmission stay | Compare the incidence of readmission and the length of readmission stay in patients receiving HiDAC 123 and HiDAC 135. | 5 months |
| Non-hematologic toxicities | Compare the differences in non-hematologic toxicities in patients receiving HiDAC 123 and HiDAC 135. | 5 months |
| Time to next treatment | Compare the time to next treatment (next chemotherapy cycle, transplant, etc.) in patients receiving HiDAC 123 and HiDAC 135. | 5 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
bone marrow, acute myeloid leukemia, high dose cytarabine, HiDAC, consolidation, chemotherapy schedule, elderly
|
|
NCT03238339
|
The Clinical Application and Popularization of Portable Home Noninvasive Ventilator
|
The subjects of this study are the chronic obstructive pulmonary disease (COPD) patients with chronic II respiratory failure. The participants will be divided into two groups: The Portable Home Noninvasive Ventilator treatment group and the routine home oxygen inhalation treatment group. All subjects will be given a stable COPD regimen and conventional oxygen therapy ,but the portable home noninvasive ventilator treatment group will need to wear a portable non-invasive ventilator. Objective evaluation indexes were established during the routine treatment, and two groups of subjects will be followed up for one year. Finally, the clinical data of all subjects will be analyzed，and then the practicability of portable wearable household noninvasive ventilator will be verified.The researchers will also build a remote breathing data-monitoring platform based on mobile internet,and a community home demonstration application point.
|
The Clinical Application and Popularization of Portable Home Noninvasive Ventilator
|
Pulmonary Disease, Chronic Obstructive, Hypercapnic Respiratory Failure
|
Inclusion Criteria:~40 years old < age < 80 years old~COPD diagnosis was made according to GOLD guidelines~The subjects with chronic type II respiratory failure~The subjects with structural lung disease~The subjects signed informed consent.~Exclusion Criteria:~The subjects suffering from COPD acute exacerbation~The subjects currently participating in other related products~The subjects with organ dysfunction because of liver,kidney, hematopoietic system and serious metabolic disease endocrine system~The subjects with poor compliance~The subjects refused to sign the informed consent
|
40 Years
|
80 Years
|
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The frequency of the chronic obstructive pulmonary disease(COPD) acute exacerbation. | Record the frequency of COPD acute exacerbation within one year | one year |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The first onset time of the chronic obstructive pulmonary disease(COPD) acute exacerbation | Record the first onset time of COPD acute exacerbation | one year |
| The number of hospitalizations due to the chronic obstructive pulmonary disease(COPD) acute exacerbation | Record the number of hospitalizations due to the COPD acute exacerbation | one year |
|
Pulmonary Disease, Chronic Obstructive, Respiratory Insufficiency, Oxygen Inhalation Therapy, Noninvasive Ventilation
|
Lung Diseases, Respiratory Insufficiency, Pulmonary Disease, Chronic Obstructive, Chronic Disease, Respiratory Tract Diseases, Respiration Disorders, Disease Attributes, Pathologic Processes, Lung Diseases, Obstructive
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| The Portable Home Noninvasive Ventilator treatment group<br>The patients maintain a stable COPD regimen, and on the basis of conventional home oxygen therapy, a portable, wearable, non-invasive ventilator will be used. | |
| Routine home oxygen therapy group<br>The patient maintained a stable COPD regimen and conventional home oxygen therapy. | |
|
The Clinical Application and Popularization of Portable Home Noninvasive Ventilator
Study Overview
=================
Brief Summary
-----------------
The subjects of this study are the chronic obstructive pulmonary disease (COPD) patients with chronic II respiratory failure. The participants will be divided into two groups: The Portable Home Noninvasive Ventilator treatment group and the routine home oxygen inhalation treatment group. All subjects will be given a stable COPD regimen and conventional oxygen therapy ,but the portable home noninvasive ventilator treatment group will need to wear a portable non-invasive ventilator. Objective evaluation indexes were established during the routine treatment, and two groups of subjects will be followed up for one year. Finally, the clinical data of all subjects will be analyzed，and then the practicability of portable wearable household noninvasive ventilator will be verified.The researchers will also build a remote breathing data-monitoring platform based on mobile internet,and a community home demonstration application point.
Official Title
-----------------
The Clinical Application and Popularization of Portable Home Noninvasive Ventilator
Conditions
-----------------
Pulmonary Disease, Chronic Obstructive, Hypercapnic Respiratory Failure
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 40 years old < age < 80 years old COPD diagnosis was made according to GOLD guidelines The subjects with chronic type II respiratory failure The subjects with structural lung disease The subjects signed informed consent. Exclusion Criteria: The subjects suffering from COPD acute exacerbation The subjects currently participating in other related products The subjects with organ dysfunction because of liver,kidney, hematopoietic system and serious metabolic disease endocrine system The subjects with poor compliance The subjects refused to sign the informed consent
Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 80 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| The Portable Home Noninvasive Ventilator treatment group<br>The patients maintain a stable COPD regimen, and on the basis of conventional home oxygen therapy, a portable, wearable, non-invasive ventilator will be used. | |
| Routine home oxygen therapy group<br>The patient maintained a stable COPD regimen and conventional home oxygen therapy. | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The frequency of the chronic obstructive pulmonary disease(COPD) acute exacerbation. | Record the frequency of COPD acute exacerbation within one year | one year |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The first onset time of the chronic obstructive pulmonary disease(COPD) acute exacerbation | Record the first onset time of COPD acute exacerbation | one year |
| The number of hospitalizations due to the chronic obstructive pulmonary disease(COPD) acute exacerbation | Record the number of hospitalizations due to the COPD acute exacerbation | one year |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pulmonary Disease, Chronic Obstructive, Respiratory Insufficiency, Oxygen Inhalation Therapy, Noninvasive Ventilation
|
|||
NCT00217932
|
Effectiveness of Divalproex Sodium (Depakote) in Treating Children With Temper Outbursts and Severe Mood Swings
|
The purpose of this study is to determine the effectiveness of divalproex sodium (Depakote) versus placebo in treating children with temper outbursts and severe mood disorders.
|
Depakote has been used to treat seizures in children for more than 20 years. The purpose of this study is to determine the effectiveness of divalproex sodium (Depakote) in treating children with temper outbursts and severe mood disorders.~This study will last 12 weeks. Participants will be randomly assigned to receive either 250 mg Depakote or placebo. The dose of medication will increase at the end of Week 1 to 500 mg of either depakote or placebo; participants will remain on this dose through Week 5. At Week 6, participants will cross-over and receive the other treatment (either depakote or placebo), which they will take through Week 12. Study visits will occur weekly and will include a physical exam, blood and urine tests, and self-reports of adverse events. In addition, caregivers will complete reports about mood swings throughout the study.
|
Double-Blind, Placebo-Controlled Study of Depakote (Divalproex Sodium) in Children With Temper Outbursts and Severe Mood Swings
|
Mood Disorders
|
* Drug: Divalproex Sodium (Depakote)
|
Inclusion Criteria:~Meets criteria for Explosive Mood Disorder (EMD)~Explosive temper as evidenced by four or more outbursts of rage, property destruction, or fighting per month~Mood liability as evidenced by multiple, daily, distinct shifts from normal to irritable mood with withdrawn or boisterous behavior, occurring without a clear precipitant~History of an EMD for one year without treatment~EMD symptoms resulting in impairment in two or more of the following areas: school, the law, family, substance use, peers, or work~EMD symptoms do not occur only during substance toxicity or withdrawal~EMD symptoms are not confined to a single setting or context~Parent and child willing to consent to study~Inadequate response to an adequate trial (8 weeks) of psychotherapy and/or family therapy~Exclusion Criteria:~Meets criteria for pervasive developmental disorder or childhood schizophrenia~Seizure or other neurologic disturbance~Pregnant~Moderate to severe mental retardation~Physical exam or laboratory results with significant abnormalities~Positive Hepatitis screen test~Liver dysfunction~Active suicidal or homicidal ideation~History of suicide attempts~History of barbiturate use~Unequivocal manic or hypomanic episode~Meets criteria for attention deficit hyperactivity disorder (ADHD) and has not failed a trial of psychostimulants for ADHD~Meets criteria for major depression in prepuberty~If female, unwilling to use an effective method of contraception for the duration of the study~Mitochondrial disease or family history of mitochondrial disease
|
7 Years
|
11 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in symptoms of explosive mood disorder; measured throughout the study and at Week 12 | | |
|
Behavioral Disorders
|
Valproic Acid, Anticonvulsants, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action, GABA Agents, Neurotransmitter Agents, Physiological Effects of Drugs, Antimanic Agents, Tranquilizing Agents, Central Nervous System Depressants, Psychotropic Drugs
|
| Intervention/Treatment |
| --- |
|Drug: Divalproex Sodium (Depakote)|nan|
|
Effectiveness of Divalproex Sodium (Depakote) in Treating Children With Temper Outbursts and Severe Mood Swings
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the effectiveness of divalproex sodium (Depakote) versus placebo in treating children with temper outbursts and severe mood disorders.
Detailed Description
-----------------
Depakote has been used to treat seizures in children for more than 20 years. The purpose of this study is to determine the effectiveness of divalproex sodium (Depakote) in treating children with temper outbursts and severe mood disorders. This study will last 12 weeks. Participants will be randomly assigned to receive either 250 mg Depakote or placebo. The dose of medication will increase at the end of Week 1 to 500 mg of either depakote or placebo; participants will remain on this dose through Week 5. At Week 6, participants will cross-over and receive the other treatment (either depakote or placebo), which they will take through Week 12. Study visits will occur weekly and will include a physical exam, blood and urine tests, and self-reports of adverse events. In addition, caregivers will complete reports about mood swings throughout the study.
Official Title
-----------------
Double-Blind, Placebo-Controlled Study of Depakote (Divalproex Sodium) in Children With Temper Outbursts and Severe Mood Swings
Conditions
-----------------
Mood Disorders
Intervention / Treatment
-----------------
* Drug: Divalproex Sodium (Depakote)
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Meets criteria for Explosive Mood Disorder (EMD) Explosive temper as evidenced by four or more outbursts of rage, property destruction, or fighting per month Mood liability as evidenced by multiple, daily, distinct shifts from normal to irritable mood with withdrawn or boisterous behavior, occurring without a clear precipitant History of an EMD for one year without treatment EMD symptoms resulting in impairment in two or more of the following areas: school, the law, family, substance use, peers, or work EMD symptoms do not occur only during substance toxicity or withdrawal EMD symptoms are not confined to a single setting or context Parent and child willing to consent to study Inadequate response to an adequate trial (8 weeks) of psychotherapy and/or family therapy Exclusion Criteria: Meets criteria for pervasive developmental disorder or childhood schizophrenia Seizure or other neurologic disturbance Pregnant Moderate to severe mental retardation Physical exam or laboratory results with significant abnormalities Positive Hepatitis screen test Liver dysfunction Active suicidal or homicidal ideation History of suicide attempts History of barbiturate use Unequivocal manic or hypomanic episode Meets criteria for attention deficit hyperactivity disorder (ADHD) and has not failed a trial of psychostimulants for ADHD Meets criteria for major depression in prepuberty If female, unwilling to use an effective method of contraception for the duration of the study Mitochondrial disease or family history of mitochondrial disease
Ages Eligible for Study
-----------------
Minimum Age: 7 Years
Maximum Age: 11 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double
Arms and Interventions
| Intervention/Treatment |
| --- |
|Drug: Divalproex Sodium (Depakote)|nan|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in symptoms of explosive mood disorder; measured throughout the study and at Week 12 | | |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Behavioral Disorders
|
|
NCT00674050
|
A Study Designed to Determine if the Drugs Albuterol (Salbutamol) and Fluticasone Have an Effect on the Pharmacokinetics of the Investigational Product Technosphere® Insulin Inhalation Powder in Healthy Volunteers
|
This study will investigate the effects of inhaled albuterol & fluticasone on one dose of TI Inhalation Powder. A total of 12 eligible subjects will be enrolled.
|
A Phase 1, Open-Label Study to Investigate the Effect of Albuterol (Salbutamol) and Fluticasone on the Pharmacokinetics of Inhaled Technosphere® Insulin Inhalation Powder in Healthy Subjects
|
Diabetes Mellitus, Healthy Subjects
|
* Drug: Technosphere Insulin (TI) Inhalation Powder
* Drug: Albuterol (Salbutamol)
* Drug: Fluticasone
|
Inclusion Criteria:~Subjects must have a fasting blood glucose (BG) level of less than 6.1 mmol/L FEV1/ FVC = LLN TLC = 80% Predicted DLco (unc) = 80% Predicted (Miller) No significant improvement in pre- to post-bronchodilator spirometry (defined as an increase of = 12% and = 200 mL in FEV1 or FVC) at Screening FEV1 = 80% (NHANES III Predicted~Exclusion Criteria:~History of diabetes mellitus Previous exposure to any inhaled insulin product Any known pulmonary disease or inability to perform PFT maneuvers meeting recommended American Thoracic Society (ATS) standards of acceptability and repeatability criteria Respiratory tract infection within 8 weeks prior to Screening/Visit 1 Major organ system diseases including seizures, heart failure, uncontrolled hypertension, aneurysm, cancer within the past 5 years, liver disease, anemia or autoimmune disorder Clinically significant abnormalities on screening laboratory evaluation Female subjects who are pregnant, lactating, or planning to become pregnant during the clinical trial period or not practicing adequate birth control Unable and/or unlikely to comprehend how to use the investigational device in this study or to follow study instructions
|
18 Years
|
55 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameters of serum insulin | | 0-360 min |
|
Healthy Males or Females subjects
|
Fluticasone, Adrenergic beta-Agonists, Albuterol, Physiological Effects of Drugs, Anti-Inflammatory Agents, Bronchodilator Agents, Autonomic Agents, Peripheral Nervous System Agents, Anti-Asthmatic Agents, Respiratory System Agents, Dermatologic Agents, Anti-Allergic Agents, Tocolytic Agents, Reproductive Control Agents, Adrenergic beta-2 Receptor Agonists, Adrenergic Agonists, Adrenergic Agents, Neurotransmitter Agents, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Technosphere Insulin (TI) Inhalation Powder<br>* 3.0 U of human insulin. 5 or 10 mg or Technosphere Inhalation Powder, containing 15 0r 30 U of insulin.<br>Drug: Albuterol (Salbutamol)<br>* 2 puff= 200ug total dose<br>Drug: Fluticasone<br>* 2 puffs= 500ug total dose<br>|
|
A Study Designed to Determine if the Drugs Albuterol (Salbutamol) and Fluticasone Have an Effect on the Pharmacokinetics of the Investigational Product Technosphere® Insulin Inhalation Powder in Healthy Volunteers
Study Overview
=================
Brief Summary
-----------------
This study will investigate the effects of inhaled albuterol & fluticasone on one dose of TI Inhalation Powder. A total of 12 eligible subjects will be enrolled.
Official Title
-----------------
A Phase 1, Open-Label Study to Investigate the Effect of Albuterol (Salbutamol) and Fluticasone on the Pharmacokinetics of Inhaled Technosphere® Insulin Inhalation Powder in Healthy Subjects
Conditions
-----------------
Diabetes Mellitus, Healthy Subjects
Intervention / Treatment
-----------------
* Drug: Technosphere Insulin (TI) Inhalation Powder
* Drug: Albuterol (Salbutamol)
* Drug: Fluticasone
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects must have a fasting blood glucose (BG) level of less than 6.1 mmol/L FEV1/ FVC = LLN TLC = 80% Predicted DLco (unc) = 80% Predicted (Miller) No significant improvement in pre- to post-bronchodilator spirometry (defined as an increase of = 12% and = 200 mL in FEV1 or FVC) at Screening FEV1 = 80% (NHANES III Predicted Exclusion Criteria: History of diabetes mellitus Previous exposure to any inhaled insulin product Any known pulmonary disease or inability to perform PFT maneuvers meeting recommended American Thoracic Society (ATS) standards of acceptability and repeatability criteria Respiratory tract infection within 8 weeks prior to Screening/Visit 1 Major organ system diseases including seizures, heart failure, uncontrolled hypertension, aneurysm, cancer within the past 5 years, liver disease, anemia or autoimmune disorder Clinically significant abnormalities on screening laboratory evaluation Female subjects who are pregnant, lactating, or planning to become pregnant during the clinical trial period or not practicing adequate birth control Unable and/or unlikely to comprehend how to use the investigational device in this study or to follow study instructions
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Technosphere Insulin (TI) Inhalation Powder<br>* 3.0 U of human insulin. 5 or 10 mg or Technosphere Inhalation Powder, containing 15 0r 30 U of insulin.<br>Drug: Albuterol (Salbutamol)<br>* 2 puff= 200ug total dose<br>Drug: Fluticasone<br>* 2 puffs= 500ug total dose<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameters of serum insulin | | 0-360 min |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Healthy Males or Females subjects
|
||
NCT01309503
|
Speech Intelligibility in Noise Using the Hearing in Noise Test (HINT)
|
The main purpose of the study is to estimate speech intelligibility in noise. A Norwegian Hearing in Noise Test (HINT) for children will be implemented, and test results for normal hearing (NH) children and adults will be collected. Test results for groups of hearing aid (HA) users and test results for cochlea implant (CI) users will be collected and compared to the NH group and between groups of HA users and CI users. A group of single sided hearing loss patients will also be included. Binaural benefits of two ears, two HAs and two CIs will be estimated.
|
Speech Intelligibility in Noise and Estimation of Binaural Benefits Using the Hearing in Noise Test (HINT). Studies on Normal Hearing Children and Adults, Groups of Hearing Aid Users and Cochlea Implant Users.
|
Speech Intelligibility
|
Inclusion Criteria for the different groups:~Normal hearing group (note that some subjects are already recruited in the normal hearing group):~audiometric thresholds less than or equal to 25 dB HL for octave frequencies between 250 Hz and 8000 Hz~Adults between age 18 and 50 years~Children at different age groups between 6 and 12 years old~Unilateral hearing loss group~Single-sided hearing loss.~Using hearing aid or willing to try hearing aid on the side with hearing loss to estimate a potential binaural benefit with hearing aid.~Unilateral hearing loss inclusion criteria is thresholds within 25 dBHL and 70 dBHL for frequencies {125,250,500} Hz. Inclusion region increasing linearly with octave frequency to 40 dBHL and 95 dBHL for frequency 8000Hz. In addition a single threshold outside this hearing threshold inclusion region is accepted.~Contralateral normal hearing with audiometric thresholds less than or equal to 25 dB HL for octave frequencies between 250 Hz and 8000 Hz~Group with Severe hearing loss at high frequencies~- Inclusion criteria is bilateral hearing loss within hearing levels where frequencies below 750 Hz can be normal or elevated down to 65 dBHL, for frequencies 1000 Hz and 1500 Hz all HL thresholds are accepted, frequencies 2000 Hz and above have threshold criteria 85 dBHL or above.~Adult CI users with unilateral and bilateral CI~All adult patients will be tested to the level of their performance.~HINT SRTs will be collected if HINT score in quiet is above 70%.~Bilateral CI users (Children)~Sequential CIs group~Children that has got two CIs in two different operations, and operations are not within one year.~Inclusion of some of the patients participating in another ongoing sequential CI-study at the ENT department,and who has a HINT score above 70% in quiet. The requirement of a quiet percentage score above 70% is due to the bilateral benefit testing/estimation.~Simultaneous CIs group~All children that has got two CIs in the same operation or sequentially within one year.~Children older than 6 years old.~Children as young as 5.5 years old can be included if they are considered ready for extended HINT testing.~Exclusion Criteria:~None
|
5 Years
|
80 Years
|
All
|
Accepts Healthy Volunteers
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Normal hearing<br>Children and adults | |
| Unilateral hearing loss<br> | |
| Severe hearing loss high frequencies<br> | |
| Adult CI users<br>Unilateral and bilateral CI | |
| Bilateral CI users<br>Children and adults~Sequential CIs~Simultaneous CIs | |
|
Speech Intelligibility in Noise Using the Hearing in Noise Test (HINT)
Study Overview
=================
Brief Summary
-----------------
The main purpose of the study is to estimate speech intelligibility in noise. A Norwegian Hearing in Noise Test (HINT) for children will be implemented, and test results for normal hearing (NH) children and adults will be collected. Test results for groups of hearing aid (HA) users and test results for cochlea implant (CI) users will be collected and compared to the NH group and between groups of HA users and CI users. A group of single sided hearing loss patients will also be included. Binaural benefits of two ears, two HAs and two CIs will be estimated.
Official Title
-----------------
Speech Intelligibility in Noise and Estimation of Binaural Benefits Using the Hearing in Noise Test (HINT). Studies on Normal Hearing Children and Adults, Groups of Hearing Aid Users and Cochlea Implant Users.
Conditions
-----------------
Speech Intelligibility
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria for the different groups: Normal hearing group (note that some subjects are already recruited in the normal hearing group): audiometric thresholds less than or equal to 25 dB HL for octave frequencies between 250 Hz and 8000 Hz Adults between age 18 and 50 years Children at different age groups between 6 and 12 years old Unilateral hearing loss group Single-sided hearing loss. Using hearing aid or willing to try hearing aid on the side with hearing loss to estimate a potential binaural benefit with hearing aid. Unilateral hearing loss inclusion criteria is thresholds within 25 dBHL and 70 dBHL for frequencies {125,250,500} Hz. Inclusion region increasing linearly with octave frequency to 40 dBHL and 95 dBHL for frequency 8000Hz. In addition a single threshold outside this hearing threshold inclusion region is accepted. Contralateral normal hearing with audiometric thresholds less than or equal to 25 dB HL for octave frequencies between 250 Hz and 8000 Hz Group with Severe hearing loss at high frequencies - Inclusion criteria is bilateral hearing loss within hearing levels where frequencies below 750 Hz can be normal or elevated down to 65 dBHL, for frequencies 1000 Hz and 1500 Hz all HL thresholds are accepted, frequencies 2000 Hz and above have threshold criteria 85 dBHL or above. Adult CI users with unilateral and bilateral CI All adult patients will be tested to the level of their performance. HINT SRTs will be collected if HINT score in quiet is above 70%. Bilateral CI users (Children) Sequential CIs group Children that has got two CIs in two different operations, and operations are not within one year. Inclusion of some of the patients participating in another ongoing sequential CI-study at the ENT department,and who has a HINT score above 70% in quiet. The requirement of a quiet percentage score above 70% is due to the bilateral benefit testing/estimation. Simultaneous CIs group All children that has got two CIs in the same operation or sequentially within one year. Children older than 6 years old. Children as young as 5.5 years old can be included if they are considered ready for extended HINT testing. Exclusion Criteria: None
Ages Eligible for Study
-----------------
Minimum Age: 5 Years
Maximum Age: 80 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Normal hearing<br>Children and adults | |
| Unilateral hearing loss<br> | |
| Severe hearing loss high frequencies<br> | |
| Adult CI users<br>Unilateral and bilateral CI | |
| Bilateral CI users<br>Children and adults Sequential CIs Simultaneous CIs | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
|
||||||
NCT01982227
|
Monocentric Prospective Pilot Study Evaluating the Value of Indocyanine Green (ICG, Indocyanine Green) During a Surgical Resection of Cancerous Lesions Peritoneal Colorectal Origin.
|
Between 30% and 40% of patients with colorectal cancer develop metastatic disease intraperitoneally. The optimal treatment of this disease combines surgery and chemotherapy but requires resection of all lesions larger than 2mm.~Indocyanine green has an affinity for tumor tissues and the interest of its use has been demonstrated for the detection of sentinel lymph node and some liver surgeries.~The ability of indocyanine green to detect peritoneal carcinomatosis in humans has never been evaluated.~This study aims to evaluate the diagnostic performance of fluorescence in the detection of malignant cells in peritoneal carcinomatosis of colorectal origin compared with pathological analysis.
|
Monocentric Prospective Pilot Study Evaluating the Value of Indocyanine Green (ICG, Indocyanine Green) During a Surgical Resection of Cancerous Lesions Peritoneal Colorectal Origin.
|
Colorectal Cancer Metastatic
|
* Drug: indocyanine green
|
Inclusion Criteria:~Patient with progressive colorectal cancer in intra-abdominal surgery requiring resection + / - Chemotherapy Hyperthermic Intraperitoneal~Aged 18 to 70 inclusive~Signature information form and consent by the patient~Exclusion Criteria:~Pregnant women, a urine pregnancy test or blood will be realized within 72 hours before surgery~Contraindication to surgery~Diagnosis not confirmed colorectal adenocarcinoma~Persons major subject of legal protection or unable to consent
|
18 Years
|
70 Years
|
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity (true positive) of the fluorescence ex vivo compared to histological analysis s detected by fluorescence ex vivo | Sensitivity (true positive) of the fluorescence ex vivo compared to histological analysis s detected by fluorescence ex vivo | At the end of the surgery |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Specificity (true negative) of the in-vivo fluorescence compared to histological analysis s detected by fluorescence ex vivo peritoneal cancer index (PCI) score with and without fluorescence | Specificity (true negative) of the in-vivo fluorescence compared to histological analysis s detected by fluorescence ex vivo PCI score with and without fluorescence | At the end of the surgery |
| Specificity (true negative) of the in-vivo fluorescence compared to histological analysis s detected by fluorescence ex vivo PCI score with and without fluorescence | Specificity (true negative) of the in-vivo fluorescence compared to histological analysis s detected by fluorescence ex vivo PCI score with and without fluorescence | At de begining of the surgery |
|
colorectal cancer metastatic, indocyanine green
|
Colorectal Neoplasms, Intestinal Neoplasms, Gastrointestinal Neoplasms, Digestive System Neoplasms, Neoplasms by Site, Neoplasms, Digestive System Diseases, Gastrointestinal Diseases, Colonic Diseases, Intestinal Diseases, Rectal Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| patients<br>Patients (Aged 18 to 70 inclusive) with progressive colorectal cancer in intra-abdominal surgery requiring resection +/- Chemotherapy Hyperthermic Intraperitoneal | Drug: indocyanine green<br>* intravenous injection (0.25mg/kg) of the indocyanine green 24h before the surgery.<br>|
|
Monocentric Prospective Pilot Study Evaluating the Value of Indocyanine Green (ICG, Indocyanine Green) During a Surgical Resection of Cancerous Lesions Peritoneal Colorectal Origin.
Study Overview
=================
Brief Summary
-----------------
Between 30% and 40% of patients with colorectal cancer develop metastatic disease intraperitoneally. The optimal treatment of this disease combines surgery and chemotherapy but requires resection of all lesions larger than 2mm. Indocyanine green has an affinity for tumor tissues and the interest of its use has been demonstrated for the detection of sentinel lymph node and some liver surgeries. The ability of indocyanine green to detect peritoneal carcinomatosis in humans has never been evaluated. This study aims to evaluate the diagnostic performance of fluorescence in the detection of malignant cells in peritoneal carcinomatosis of colorectal origin compared with pathological analysis.
Official Title
-----------------
Monocentric Prospective Pilot Study Evaluating the Value of Indocyanine Green (ICG, Indocyanine Green) During a Surgical Resection of Cancerous Lesions Peritoneal Colorectal Origin.
Conditions
-----------------
Colorectal Cancer Metastatic
Intervention / Treatment
-----------------
* Drug: indocyanine green
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient with progressive colorectal cancer in intra-abdominal surgery requiring resection + / - Chemotherapy Hyperthermic Intraperitoneal Aged 18 to 70 inclusive Signature information form and consent by the patient Exclusion Criteria: Pregnant women, a urine pregnancy test or blood will be realized within 72 hours before surgery Contraindication to surgery Diagnosis not confirmed colorectal adenocarcinoma Persons major subject of legal protection or unable to consent
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| patients<br>Patients (Aged 18 to 70 inclusive) with progressive colorectal cancer in intra-abdominal surgery requiring resection +/- Chemotherapy Hyperthermic Intraperitoneal | Drug: indocyanine green<br>* intravenous injection (0.25mg/kg) of the indocyanine green 24h before the surgery.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity (true positive) of the fluorescence ex vivo compared to histological analysis s detected by fluorescence ex vivo | Sensitivity (true positive) of the fluorescence ex vivo compared to histological analysis s detected by fluorescence ex vivo | At the end of the surgery |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Specificity (true negative) of the in-vivo fluorescence compared to histological analysis s detected by fluorescence ex vivo peritoneal cancer index (PCI) score with and without fluorescence | Specificity (true negative) of the in-vivo fluorescence compared to histological analysis s detected by fluorescence ex vivo PCI score with and without fluorescence | At the end of the surgery |
| Specificity (true negative) of the in-vivo fluorescence compared to histological analysis s detected by fluorescence ex vivo PCI score with and without fluorescence | Specificity (true negative) of the in-vivo fluorescence compared to histological analysis s detected by fluorescence ex vivo PCI score with and without fluorescence | At de begining of the surgery |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
colorectal cancer metastatic, indocyanine green
|
||
NCT02531633
|
Efficacy and Safety Study of Sirukumab in Patients With Giant Cell Arteritis
|
Sirukumab is a fully human anti-interleukin-6 (IL-6) immunoglobulin G1-kappa with a high affinity and specificity for binding to the human IL-6 molecule that may have therapeutic benefit in the treatment of giant cell arteritis (GCA) by interruption of multiple pathogenic pathways. Sirukumab inhibits IL-6-mediated signal transducer and activator of transcription 3 (STAT3) phosphorylation, resulting in the inhibition of the biological effect of IL-6. This study will evaluate the efficacy and safety of sirukumab to characterize the benefit-to-risk profile of sirukumab in the treatment of active GCA. The study will be conducted in 2 distinct parts (Part A and Part B) and consists of the following phases: Screening phase, Part A: 52-week double-blind treatment phase, Part B: 104-week extension phase with the option to receive open-label sirukumab based on disease status and a 16-week follow-up phase if applicable.~Approximately 204 subjects with a diagnosis of GCA and active disease within 6 weeks of baseline will be randomized into Part A, the 52-week double-blind treatment phase, to receive one of two doses of sirukumab or placebo, each in addition to a pre-specified prednisone taper. The efficacy and safety of sirukumab in sustaining remission will be assessed at Week 52. Subjects completing Part A of the study will be eligible to enter Part B, the 104-week extension phase, designed to investigate the long-term maintenance of remission and safety following cessation of sirukumab treatment and to assess long-term corticosteroid use. Subjects with active GCA at the end of Part A or those with new onset of GCA flare during the first 52 weeks of Part B will be eligible to receive open-label sirukumab. Subjects will need to have follow-up safety evaluations for at least 16 weeks after receiving the last dose of study drug, applicable only for those who are withdrawn prematurely from the study or whose open-label sirukumab treatment in Part B completes after Week 88.
|
A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Sirukumab in the Treatment of Patients With Giant Cell Arteritis
|
Giant Cell Arteritis
|
* Drug: Sirukumab
* Drug: Placebo to match sirukumab
* Drug: Prednisone
* Drug: Placebo to match prednisone
|
Inclusion Criteria:~Diagnosis of GCA defined by the following Revised GCA Diagnosis Criteria:~Age >=50 years. History of ESR >=50 millimeter/hour (mm/hour) or CRP >=2.45 milligram/deciliter(mg/dL).~Presence of at least one of the following: Unequivocal cranial symptoms of GCA; Unequivocal symptoms of polymyalgia rheumatic (PMR).~Presence of at least one of the following: Temporal artery biopsy revealing features of GCA; Evidence of large-vessel vasculitis by angiography or cross-sectional imaging.~Active GCA within 6 weeks of Randomization (Baseline) where active disease is defined by an ESR >=30 mm/hr or CRP >=1 mg/dL AND the presence of at least one of the following:~Unequivocal cranial symptoms of GCA; Unequivocal symptoms of PMR; Other features judged by the clinician investigator to be consistent with GCA or PMR flares.~At screening, receiving or able to receive prednisone 20-60 mg/day for the treatment of active GCA.~Clinically stable GCA disease at baseline such that the subject is able to safely participate in the blinded prednisone taper regimen in the opinion of the investigator.~Practicing acceptable methods of birth control if a female of child-bearing potential.~No evidence of active or latent infection with Mycobacterium tuberculosis (TB).~Exclusion Criteria:~Are pregnant or breastfeeding.~Recent (within the past 12 weeks) or planned major surgery that would impact on study procedures or assessments.~Organ transplantation recipients (except corneas within 3 months prior to baseline visit).~Had prior treatment with any of the following:~Systemic immunosuppressives) within 4 weeks of baseline; Biologic agents targeted at reducing tumor necrosis factor-alpha (TNF-alpha) within 2-8 weeks of baseline, depending on the agent; Any prior use of tocilizumab or other anti-IL-6 agents; B-cell depleting agents (eg, rituximab) within 12 months prior to baseline or longer if B cell counts have not returned to normal range or baseline levels; Cytotoxic drugs such as cyclophosphamide, chlorambucil, nitrogen mustard, or other alkylating agents within 4 weeks of baseline; Abatacept within 8 weeks of baseline; Tofacitinib within 4 weeks of baseline; Methotrexate use within 2 weeks of baseline.~Methylprednisolone > 100 mg/day intravenous (IV) (or equivalent) within 8 weeks of baseline.~History of severe allergic reactions to monoclonal antibodies, human proteins, or excipients.~Evidence of serious concomitant disease, which in the opinion of the investigator makes them unsuitable for participation in the study.~Major ischemic event, unrelated to GCA, within 12 weeks of screening.~Marked baseline prolongation of corrected QT (QTc) interval >= 450 milliseconds (msec) (QTc by Bazett's formula [QTcB ]or QTc by Fridericia's formula [QTcF] ), history of Torsade de Pointes, family history of long QT syndrome, history of second or third degree heart block.~Current liver disease that could interfere with the trial~History of or current active diverticulitis, inflammatory bowel disease, or other symptomatic gastrointestinal tract condition that might predispose to bowel perforation.~History of known demyelinating diseases such as multiple sclerosis or optic neuritis.~Active infections, or history of recurrent infections or have required management of acute or chronic infections, as follows:~Currently on any suppressive therapy for a chronic infection, history or suspicion of chronic infection, hospitalization for treatment of infection within 60 days of the baseline visit, or use of parenteral (IV) or intra-muscular [IM]) antimicrobials within 60 days of baseline or oral antimicrobials within 30 days of baseline~Primary or secondary immunodeficiency or any other autoimmune disease.~Human immunodeficiency virus (HIV) infection, hepatitis C or hepatitis B infection~Live virus or bacterial vaccination within 3 months before the first administration of study drug
|
50 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Number of Participants in Sustained Remission at Week 52 | Sustained remission was defined as having achieved all of the following: 1) remission at Week 12, 2) absence of disease flare Week 12 through Week 52, 3) completion of the assigned prednisone taper, and 4) no requirement for rescue therapy through Week 52. Remission was defined as absence of clinical signs and symptoms of GCA and normalization of erythrocyte sedimentation rate (ESR) [<30 millimeters per hour] and C-reactive Protein (CRP) [<1 milligram/deciliter]) and flare was defined as recurrence of symptoms attributable to active GCA, with or without elevations in ESR and/or CRP. Data for number of participants in sustained remission at Week 52 is presented. Only those participants who completed Week 52 visit or withdrew before 10 Oct 2017 were included in the analysis. | Week 52 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part B: Number of Participants Who Remained in Sustained Remission Without Requirement for Rescue Therapy or Treatment Change at Week 24 | Participants who remained in sustained remission without requirement for rescue therapy or treatment change at each scheduled visit of Part B were defined as participants having achieved all of the following criteria: 1. Participants in sustained remission at the Week 52 visit of Part A, 2. Absence of disease flare, 3. No requirement for rescue therapy at any time through Week 24 of Part B, 4. No requirement for treatment change at any time through Week 24 of Part B. Remission was defined as absence of clinical signs and symptoms of GCA and normalization of ESR [<30 millimeters per hour] and CRP [<1 milligram/deciliter]) and flare was defined as recurrence of symptoms attributable to active GCA, with or without elevations in ESR and/or CRP. | Week 24 |
| Part A: Cumulative Prednisone Dose Over Time | Cumulative prednisone is the dose from the taper (both open-label and blinded) as well as from the corticosteroid rescue therapies. Cumulative dose at the specified Week was derived as the sum of all the doses from Baseline to the specified Week at each visit was calculated based on the number of participants who attended that visit. For the main analysis of cumulative prednisone dose over time. Data for Prednisone Dose- Study Drug and Prednisone Equivalent Concomitant Therapy for part A is presented. ITT population and the number of participants included at specific time points were based on the participants who attended a scheduled or unscheduled visit mapped to that time point and received a total prednisone dose greater than 0 mg. | Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 |
| Part B: Number of Participants in Sustained Remission Over Time | Sustained remission was defined as having achieved all of the following: 1) remission at Week 12 (absence of signs and symptoms of GCA and normalization of ESR and CRP), 2) absence of disease flare Week 12 through Week 52 with or without elevations in ESR and/or CRP, 3) completion of the assigned prednisone taper, and 4) no requirement for rescue therapy through Week 52. Remission was defined as absence of clinical signs and symptoms of GCA and normalization of ESR [<30millimeters per hour] and CRP [<1milligram/deciliter]) and Flare was defined as recurrence of symptoms attributable to active GCA, with or without elevations in ESR and/or CRP. Data for number of participants in sustained remission over time for Part B is presented. Only participants who were in sustained remission at Week 52 of Part A, who Completed the Week X Visit of Part B or who Withdraw before 10th of October 2017 were included in the analysis. | Weeks 4, 8 and 12 |
| Part A: Time to First Disease Flare After Clinical Remission | Clinical remission was defined as absence of clinical signs and symptoms of GCA, which was determined by a lack of flare for the participant. If a participant had a flare, they had one or more signs and symptoms, and therefore are not considered as being in clinical remission. Time to first disease flare (days) was calculated as (Date of First Flare - Date of Clinical Remission + 1 day). Data for Time to first disease flare after clinical remission for part A is presented. | Week 52 |
| Part B: Time to First Disease Flare for Participants in Sustained Remission | Clinical remission was defined as absence of clinical signs and symptoms of GCA. If a participant had a flare, they had one or more signs and symptoms, and therefore are not considered as being in clinical remission. Time to event (days) is defined as the duration in days from the date of the Week 52 visit of Part A to the start date of Event (Date of First Flare - Date of Week 52 visit of Part A + 1). Data for Time to first disease flare after clinical remission for part B is presented. | Week 52 |
| Part A: Number of Disease Flares Over Time | This summarizes disease flares over time with no adjustment for exposure to study drugs, calculated by taking the last visit before a participant withdrew and then counting the number of participants with at least 1 flare up to that point and summing up the total number of flares experienced by each of these participants; participants who did not reach Week 2 were not included in this analysis. Data for number of disease flares per participant over time for part A were presented. | Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 |
| Part A: Number of Participants With at Least One Hospitalization for Disease Flare | Number of participants with at least one hospitalization for disease flare at a given visit is the number of participants with at least one hospitalization for disease flare between first SC IP intake and the day of the given visit. Data for participants requiring at least one hospitalization for disease flare for part A is presented. | Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 |
| Part A: Number of Hospitalizations for Disease Flare Over Time | Number of hospitalizations for disease flare at given visit is the number of hospitalizations for disease flare between first SC IP intake and the day of the of the given visit.. Data for number of hospitalizations for disease flare over time for part A was presented. | Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 |
| Part A: Mean 36-item Short Form Health Survey Version 2 (SF-36 v2) Acute Score Over Time | SF-36v2 acute health survey questionnaire consists of the following 8 multi-item scales: 1. Limitations in physical functioning due to health problems, 2. Limitations in usual role activities due to physical health problems, 3. Bodily pain, 4. General mental health (psychological distress and well-being), 5. Limitations in usual role activities due to personal or emotional problems, 6. Limitations in social functioning due to physical or mental health problems. 7. Vitality (energy and fatigue) and 8. General health perception. These 8 scales were scored from 0 to 100, 0 (worst score) to 100 (best score) where higher scores indicates better health. Data for Physical Component Summary (PCS), Mental Component Summary (MCS) scores was presented. | Baseline (Week 0), Weeks 12, 24, 36, 52 |
| Part A: Mean EuroQol - 5 Dimensions, 5 Levels (EQ-5D-5L) Index Score Over Time | EuroQoL-5 Dimensions consist of 2 elements: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D descriptive system comprised of following 5 dimensions: 1.Mobility, 2.Self-Care, 3.Usual Activities, 4.Pain/Discomfort and 5.Anxiety/Depression. Each of these 5 dimensions has 5 levels: 1: no problems; 2: slight problems; 3: moderate problems; 4: severe problems; 5: Unable to do. The digits for each of 5 dimensions were combined in a 5-digit number describing the participant's health state: e.g. state 11111 indicates no problem on any of the 5 dimensions. Index score was derived from the 5 dimensions scores using UK tariff. The weights based from the UK population was used for conversion, regardless of the origin country of participant. The score ranged from -0.594 (worst score) to 1.000 (best score). | Baseline (Week 0) and Weeks 12, 24, 36, 52 |
| Part A: Mean EQ-5D-5L Visual Analogue Scale (VAS) Over Time | EQ-5D essentially consists of 2 elements: the EQ-5D descriptive system and the EQ VAS. The EQ-5D descriptive system comprised of the following 5 dimensions: 1.Mobility, 2.Self-Care, 3.Usual Activities, 4.Pain/Discomfort and 5.Anxiety/Depression. Each of these 5 dimensions has 5 levels: 1: no problems; 2: slight problems; 3: moderate problems; 4: severe problems; 5: Unable to do. The digits for each of the 5 dimensions were combined in a 5-digit number describing the participant's health state: e.g. state 11111 indicates no problem on any of the 5 dimensions. The index score was derived from the 5 dimensions scores using UK tariff. The weights based from the UK population was used for the conversion, regardless of the origin country of participant. The score ranged from -0.594 (worst score) to 1 (best score). The EQ VAS records the respondent's self-rated health on a vertical line, VAS where the endpoints are 'Best imaginable health state' and 'Worst imaginable health state'. | Baseline (Week 0) and Weeks 12, 24, 36, 52 |
| Part A: Mean Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-Fatigue) Scores Over Time | The FACIT-Fatigue is a 13-item questionnaire formatted for self-administration that assesses participant reported fatigue and its impact upon daily activities and function over the past seven days. Participants were asked to answer each question using a 5-point Likert-type scale (4 = Not at all; 3 = A little bit; 2 = Somewhat; 3 = Quite a bit; and 0 = Very Much) where 0 is a bad response and 4 is good response. Each of the 13 items of the FACIT-Fatigue Scale ranges from 0-4, with a range of possible total score from 0-52, 0 (Extreme fatigue) to 52 (No fatigue) where 0 being the worst possible score and 52 the best (i.e. less fatigue). Scores below 30 indicate severe fatigue. Each negatively-worded item response was recoded so that 0 is a bad response and 4 is good response. All responses were added with equal weight to obtain the total score. The total score was calculated as the sum of all the individual items after recoding some of the items. | Baseline (Week 0), Weeks 12, 24, 36, 52 |
| Part A: Mean Pain Numeric Rating Scale (NRS) Scores Over Time | The assessment of pain severity was made using a single pain severity item on which participants were asked to rate the severity of their average pain on a 11-point numeric rating scale ranging from 0, no pain to 10, the worst pain imaginable. Data for NRS scores over time for part A is reported. | Baseline (Week 0), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 |
| Part A: Mean Health Assessment Questionnaire - Disability Index (HAQDI) Score Over Time | Health Assessment Questionnaire-Disability Index (HAQ-DI) indicates the extent of participant's functional ability during the past week, and was assessed for subgroup of participants with symptoms of Polymyalgia Rheumatic (PMR). HAQ-DI included 20 questions in 8 categories of functioning - dressing and grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Each functional area contains at least two questions. For each question, there is a 4-level difficulty scale that is scored from 0 (minimum) to 3 (Maximum), representing no difficulty (0), some difficulty (1), much difficulty (2), and unable to do (3) where, lower score indicates less disability and higher scores indicates worse disability. Total score was calculated as average scores of 20 questions which can be interpreted in terms of 3 categories: from 0 to 1: mild difficulties to moderate disability, from 1 to 2: disability moderate to severe, from 2 to 3: severe to very severe disability. | Baseline (Week 0) and Weeks 12, 24, 36 and 52 |
| Part A: Number of Participants With Patient Global Impression of Change (PGIC) Score Over Time | Patient-reported response to treatment was assessed using the PGIC measure, a single item completed by participant to provide a clinically meaningful summary of an individual's response to treatment. The assessment provides an estimate of the magnitude of treatment response at different time points during the study. Responses include: Much Better, Better, Slightly Better, No Change, Slightly Worse, Worse, and Much Worse. The categorical data of participant rating of change is summarized by treatment group, visit and response category. | Weeks 12, 24 and 52 |
| Part A: Mean Patient Global Assessment of Disease Activity (PtGA) Score Over Time | The Patient's Global Assessments of Disease Activity was recorded on a Visual analog scale (VAS) of 10 centimeter (cm) ranging from 0 (very well) to 10 (very poor). | Baseline (Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 |
| Part A: Mean Physician Global Assessment of Disease Activity (PhGA) Score Over Time | The Physician's Global Assessments of Disease Activity was recorded on a VAS of 10 cm ranging from 0 (none) to 10 (extremely active). | Baseline (Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 |
| Part A: Change From Baseline in Serum C Reactive Protein (CRP) Over Time | Blood samples were collected for analysis of CRP. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for Change from Baseline in serum CRP over time for part A was reported. The Safety set comprised of all randomized participants who received at least 1 dose of SC IP. | Baseline (Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 |
| Part A: Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Over Time | Blood samples were collected for analysis of ESR. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for Change from Baseline in ESR over time for part A was reported. | Baseline (Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 |
| Part A: Number of Participants With Adverse Events (AEs), Serious AEs (SAEs) and Corticosteroid Related AEs | An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinaemia were categorized as SAE. Number of participants with AEs, SAEs and corticosteroid related AEs have been reported. | Up to 52 weeks |
| Part A: Change From Baseline in : Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP and DBP were measured in semi-supine position after 5 minutes rest at indicated time points. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Week 0), Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 |
| Part A: Change From Baseline in Pulse Rate | Pulse rate was measured in semi-supine position after 5 minutes rest at Baseline and up to 52 weeks. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Week 0) and Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 |
| Part A: Change From Baseline in Temperature | Temperature was measured in semi-supine position after 5 minutes rest at Baseline and up to 52 weeks. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Week 0) and Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 |
| Part A: Change From Baseline in Hematology Parameters- Eosinophils, Leukocytes, Lymphocytes, Neutrophils and Platelets | Blood samples were collected to analyze the hematology parameters including Eosinophils, Leukocytes, Lymphocytes, Neutrophils and Platelets. Change from Baseline is presented for these parameters. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Week 0) and Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 |
| Part A: Change From Baseline in Hematology Parameters- Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin | Blood samples were collected to analyze the hematology parameters including MCHC and Hemoglobin. Change from Baseline is presented for these parameters. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Week 0) and Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 |
| Part A: Change From Baseline in Hematology Parameter-Hematocrit | Blood samples were collected to analyze the hematology parameter Hematocrit. Change from Baseline is presented for this parameter. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Week 0) and Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 |
| Part A: Change From Baseline in Hematology Parameter -Erythrocytes Mean Corpuscular Volume | Blood samples were collected to analyze the hematology parameter Erythrocytes Mean Corpuscular Volume. Change from Baseline is presented for this parameter. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Week 0) and Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 |
| Part A:Change From Baseline in Hematology Parameter-Erythrocytes Mean Corpuscular Hemoglobin | Blood samples were collected to analyze the hematology parameter Erythrocytes Mean Corpuscular Hemoglobin. Change from Baseline is presented for this parameter. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Week 0) and Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 |
| Part A:Change From Baseline in Hematology Parameter- Erythrocytes | Blood samples were collected to analyze the hematology parameter Erythrocytes. Change from Baseline is presented for this parameter. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Week 0) and Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 |
| Part A: Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide, Chloride, Glucose, Phosphate, Potassium, Sodium and Urea | Blood samples were collected to analyze the chemistry parameters including Calcium, Carbon Dioxide, Chloride, Glucose, Phosphate, Potassium, Sodium and Urea . Change from Baseline is presented for these parameters. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Week 0) and Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 |
| Part A: Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein | Blood samples were collected to analyze the chemistry parameters including Albumin and Protein. Change from Baseline is presented for these parameters. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 |
| Part A: Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST) | Blood samples were collected to analyze the chemistry parameters including ALT,ALP and AST. Change from Baseline is presented for these parameters. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 |
| Part A: Change From Baseline in Clinical Chemistry Parameters: Bilirubin, Creatinine, Direct Bilirubin and Indirect Bilirubin | Blood samples were collected to analyze the chemistry parameters including bilirubin, creatinine, direct bilirubin and indirect bilirubin. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 |
| Part A: Mean Serum Concentrations of Sirukumab | Blood samples for Pharmacokinetic analysis of sirukumab serum concentrations were planned to be collected at specified time points. | Baseline (Week 0), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 44 and 52 |
| Part A: Mean Serum Anti-sirukumab Antibodies | Blood samples for Pharmacokinetic analysis of Serum anti-sirukumab antibodies were planned to be collected at specified time points. | Baseline (Week 0) and up to 52 weeks |
| Part A: Change From Baseline in Free and Total Interleukin-6 (IL-6) Over Time | Blood samples for Pharmacodynamic analysis were planned but not collected due to early termination of study. | Baseline (Week 0) and up to 52 weeks |
| Part B: Number of Participants With AEs, SAEs and Corticosteroid Related AEs Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B | An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinaemia were categorized as SAE. Number of participants with AEs, SAEs and corticosteroid related AEs for part B have been reported. | Up to 120 weeks |
| Part B: Number of Participants With AEs, SAEs and Corticosteroid Related AEs Who Never Received 100mg OL Sirukumab in Part B | An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinaemia were categorized as SAE. Number of participants with AEs, SAEs and corticosteroid related AEs for part B have been reported. | Up to 120 weeks |
| Part B: Change From Baseline in SBP and DBP for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B | SBP and DBP were measured in semi-supine position after 5 minutes rest for the participant. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented. | Baseline (Week 0) and Weeks 2,4,8,12,14,16,24,36,38,40 and follow up (Week 120) |
| Part B: Change From Baseline in SBP and DBP for Participants Who Never Received 100 mg Open Label Sirukumab in Part B | SBP and DBP were measured in semi-supine position after 5 minutes rest for the participant. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented. | Baseline (Week 0) and Weeks 4,8,12,16,24,36 and follow up (Week 120) |
| Part B: Change From Baseline in Pulse Rate for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B | Pulse rate was measured in semi-supine position after 5 minutes rest. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented. | Baseline (Week 0) and Weeks 2,4,8,12,14,16,24,36,38,40 and follow up (Week 120) |
| Part B: Change From Baseline in Pulse Rate for Participants Who Never Received 100 mg Open Label Sirukumab in Part B | Pulse rate was measured in semi-supine position after 5 minutes rest. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab is presented. | Baseline (Week 0) and Weeks 4,8,12,16,24,36 and follow up (Week 120) |
| Part B: Change From Baseline in Temperature for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B | Temperature was measured in semi-supine position after 5 minutes rest.. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented. | Baseline (Week 0) and Weeks 2,4,8,12,14,16,24,36,38,40 and follow up (Week 120) |
| Part B: Change From Baseline in Temperature for Participants Who Never Received 100 mg Open Label Sirukumab in Part B | Temperature was measured in semi-supine position after 5 minutes rest.. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented. | Baseline (Week 0) and Weeks 4,8,12,16,24,36 and follow up (Week 120) |
| Part B: Change From Baseline in Hematology Parameters- Eosinophils, Leukocytes, Lymphocytes, Neutrophils and Platelets for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B | Blood samples were collected to analyze the hematology parameters including Eosinophils, Leukocytes, Lymphocytes, Neutrophils and Platelets. Change from Baseline is presented for these parameters.Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented. | Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 |
| Part B: Change From Baseline in Hematology Parameters- Eosinophils, Leukocytes, Lymphocytes, Neutrophils and Platelets for Participants Who Never Received 100 mg Open Label Sirukumab in Part B | Blood samples were collected to analyze the hematology parameters including Eosinophils, Leukocytes, Lymphocytes, Neutrophils and Platelets. Change from Baseline is presented for these parameters.Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented. | Baseline (Week 0) and Weeks 4,8,12,16,24 and 36 |
| Part B: Change From Baseline in Hematology Parameters- MCHC and Hemoglobin for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B | Blood samples were collected to analyze the hematology parameters including MCHC and Hemoglobin. Change from Baseline is presented for these parameters. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented. | Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 |
| Part B: Change From Baseline in Hematology Parameters- MCHC and Hemoglobin for Participants Who Never Received 100 mg Open Label Sirukumab in Part B | Blood samples were collected to analyze the hematology parameters including MCHC and Hemoglobin. Change from Baseline is presented for these parameters. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented. | Baseline (Week 0) and Weeks 4,8,12,16,24 and 36 |
| Part B: Change From Baseline in Hematology Parameter-Hematocrit for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B | Blood samples were collected to analyze the hematology parameter Hematocrit. Change from Baseline is presented for this parameter. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented. | Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 |
| Part B: Change From Baseline in Hematology Parameter-Hematocrit for Participants Who Never Received 100 mg Open Label Sirukumab in Part B | Blood samples were collected to analyze the hematology parameter Hematocrit. Change from Baseline is presented for this parameter. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented. | Baseline (Week 0) and Weeks 4,8,12,16,24 and 36 |
| Part B: Change From Baseline in Hematology Parameter -Erythrocytes Mean Corpuscular Volume for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B | Blood samples were collected to analyze the hematology parameter Erythrocytes Mean Corpuscular Volume. Change from Baseline is presented for this parameter. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented. | Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 |
| Part B: Change From Baseline in Hematology Parameter -Erythrocytes Mean Corpuscular Volume for Participants Who Never Received 100 mg Open Label Sirukumab in Part B | Blood samples were collected to analyze the hematology parameter Hematocrit. Change from Baseline is presented for this parameter. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented. | Baseline (Week 0) and Weeks 4,8,12,16,24 and 36 |
| Part B: Change From Baseline in Hematology Parameter-Erythrocytes Mean Corpuscular Hemoglobin for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B | Blood samples were collected to analyze the hematology parameter Erythrocytes Mean Corpuscular Hemoglobin. Change from Baseline is presented for this parameter. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL Sirukumab is presented. | Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 |
| Part B: Change From Baseline in Hematology Parameter-Erythrocytes Mean Corpuscular Hemoglobin for Participants Who Never Received 100 mg Open Label Sirukumab in Part B | Blood samples were collected to analyze the hematology parameter Erythrocytes Mean Corpuscular Hemoglobin. Change from Baseline is presented for this parameter. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented. | Baseline (Week 0) and Weeks 4,8,12,16,24 and 36 |
| Part B: Change From Baseline in Hematology Parameter- Erythrocytes for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B | Blood samples were collected to analyze the hematology parameter Erythrocytes. Change from Baseline is presented for this parameter. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL Sirukumab is presented. | Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 |
| Part B: Change From Baseline in Hematology Parameter- Erythrocytes for Participants Who Never Received 100 mg Open Label Sirukumab in Part B | Blood samples were collected to analyze the hematology parameter Erythrocytes. Change from Baseline is presented for this parameter. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented. | Baseline (Week 0) and Weeks 4,8,12,16,24 and 36 |
| Part B: Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide, Chloride, Glucose, Phosphate, Potassium, Sodium and Urea for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B | Blood samples were collected to analyze the chemistry parameters including Calcium, Carbon Dioxide, Chloride, Glucose, Phosphate, Potassium, Sodium and Urea. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL Sirukumab is presented. | Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 |
| Part B: Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide, Chloride, Glucose, Phosphate, Potassium, Sodium and Urea for Participants Who Never Received 100 mg Open Label Sirukumab in Part B | Blood samples were collected to analyze the chemistry parameters including Calcium, Carbon Dioxide, Chloride, Glucose, Phosphate, Potassium, Sodium and Urea. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented. | Baseline (Week 0) and Weeks 4,8,12,16,24 and 36 |
| Part B: Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B | Blood samples were collected to analyze the chemistry parameters including Albumin and Protein. Change from Baseline is presented for these parameters. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented. | Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 |
| Part B: Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein for Participants Who Never Received 100 mg Open Label Sirukumab in Part B | Blood samples were collected to analyze the chemistry parameters including Albumin and Protein. Change from Baseline is presented for these parameters. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented. | Baseline (Week 0) and Weeks 4,8,12,16,24 and 36 |
| Part B: Change From Baseline in Clinical Chemistry Parameters: ALT, ALP and AST for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B | Blood samples were collected to analyze the chemistry parameters including ALT,ALP and AST. Change from Baseline is presented for these parameters. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented. | Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 |
| Part B: Change From Baseline in Clinical Chemistry Parameters: ALT, ALP and AST for Participants Who Never Received 100 mg Open Label Sirukumab in Part B | Blood samples were collected to analyze the chemistry parameters including ALT,ALP and AST. Change from Baseline is presented for these parameters. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented | Baseline (Week 0) and Weeks 4,8,12,16,24 and 36 |
| Part B: Change From Baseline in Clinical Chemistry Parameters: Bilirubin, Creatinine, Direct Bilirubin and Indirect Bilirubin for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B | Blood samples were collected to analyze the chemistry parameters including Albumin and Protein. Change from Baseline is presented for these parameters. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented. | Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 |
| Part B: Change From Baseline in Clinical Chemistry Parameters: Bilirubin, Creatinine, Direct Bilirubin and Indirect Bilirubin for Participants Who Never Received 100 mg Open Label Sirukumab in Part B | Blood samples were collected to analyze the chemistry parameters including Albumin and Protein. Change from Baseline is presented for these parameters. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented. | Baseline (Week 0) and Weeks 4,8,12,16,24 and 36 |
| Part B: Cumulative Prednisone Dose Over Time for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B | Cumulative prednisone dose is the cumulative doses taken from start of Part B. The cumulative prednisone dose at each visit was calculated based on the number of participants who attended that visit. Data for participants who received at least one dose of 100mg open label Sirukumab was presented. | Weeks 2, 4, 8, 12, 14, 16, 24, 28, 32 and 38 |
| Part B: Cumulative Prednisone Dose Over Time for Participants Who Never Received 100 mg Open Label Sirukumab in Part B | Cumulative prednisone dose is the cumulative doses taken from start of Part B. The cumulative prednisone dose at each visit was calculated based on the number of participants who attended that visit. Data for participants who never received 100 mg open label Sirukumab has been presented. | Weeks 2, 4, 8, 12, 14, 16, 24, 28, 32 and 38 |
| Part B: Number of Disease Flares Over Time | This summarizes disease flares over time with no adjustment for exposure to study drugs, calculated by taking the last visit before a participant withdrew and then counting the number of participants with at least 1 flare up to that point and summing up the total number of flares experienced by each of these participants. Data for number of disease flares per participant over time for part B were presented. | Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 |
| Part B: Number of Participants Requiring at Least One Hospitalization for Disease Flare | Number of participants with at least one flare at a given visit was the number of participants with at least one flare between first SC IP intake and the day of the given visit. The hospitalizations for disease flare were planned to be identified through the adjudication of adverse events of special interest, and include events from the category: Severe Flare including Hospitalizations. Data for participants requiring hospitalizations for disease flare for part B was not available due to early termination of study. | Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 |
| Part B: Number of Hospitalizations for Disease Flare Over Time | Number of participants with at least one flare at a given visit was the number of participants with at least one flare between first SC IP intake and the day of the given visit. The hospitalizations for disease flare were planned to be identified through the adjudication of adverse events of special interest, and include events from the category: Severe Flare including Hospitalizations. Data for participants requiring hospitalizations for disease flare for part B was not available due to early termination of study. | Up to Week 104 |
| Part B: Change From Baseline in 36-item SF-36 v2 Acute Score Over Time for Participants Who Received at Least One Dose of 100 mg OL Sirukumab in Part B | SF-36v2 acute health survey questionnaire was developed as part of the Rand Health Insurance Experiment and consists of the following 8 multi-item scales: 1. Limitations in physical functioning due to health problems, 2. Limitations in usual role activities due to physical health problems, 3. Bodily pain, 4. General mental health (psychological distress and well-being), 5. Limitations in usual role activities due to personal or emotional problems, 6. Limitations in social functioning due to physical or mental health problems. 7. Vitality (energy and fatigue) and 8. General health perception. These 8 scales were scored from 0 to 100, 0 (worst score) to 100 (best score) where higher scores indicates better health. Data for participants (Par) who received at least one dose of 100 mg OL Sirukumab has been presented. Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Day 0), Day 85, Day 87, Day 91, Day 113, Day 162, Day 339, Day 344, Week 12 and Week 24 |
| Part B: Change From Baseline in 36-item SF-36 v2 Acute Score Over Time for Participants Who Never Received 100 mg OL Sirukumab in Part B | SF-36v2 acute health survey questionnaire was developed as part of the Rand Health Insurance Experiment and consists of the following 8 multi-item scales: 1. Limitations in physical functioning due to health problems, 2. Limitations in usual role activities due to physical health problems, 3. Bodily pain, 4. General mental health (psychological distress and well-being), 5. Limitations in usual role activities due to personal or emotional problems, 6. Limitations in social functioning due to physical or mental health problems. 7. Vitality (energy and fatigue) and 8. General health perception. These 8 scales were scored from 0 to 100, 0 (worst score) to 100 (best score) where higher scores indicates better health. Data for participants (Par) who never received 100 mg OL Sirukumab has been presented. Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Day 0) and Day 23, Day 29, Day 30, Day 57, Day 59, Day 64, Day 65 , Day 85, Day 112, Day 113, Day 163, Day 169, Day 373, Week 8 and Week 12 |
| Part B: Change From Baseline in EQ-5D-5L Index Score Over Time for Participants Who Received at Least One Dose of 100 mg OL Sirukumab in Part B | EuroQoL-5 Dimensions consist of 2 elements: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D descriptive system comprised of following 5 dimensions: 1.Mobility, 2.Self-Care, 3.Usual Activities, 4.Pain/Discomfort and 5.Anxiety/Depression. Each of these 5 dimensions has 5 levels: 1: no problems; 2: slight problems; 3: moderate problems; 4: severe problems; 5: Unable to do. The digits for each of 5 dimensions were combined in a 5-digit number describing the participant's health state: e.g. state 11111 indicates no problem on any of the 5 dimensions. Index score was derived from the 5 dimensions scores using UK tariff. The weights based from the UK population was used for conversion, regardless of the origin country of participant. The score ranged from -0.594 (worst score) to 1.000 (best score). Baseline was last measurement done up to and including Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Day 0) and Day 85, Day 87, Day 91, Day 113, Day 162, Day 339, Day 344, Week 12 and Week24 |
| Part B: Change From Baseline in EQ-5D-5L Index Score Over Time for Participants Who Never Received 100mg OL Sirukumab in Part B | EuroQoL-5 Dimensions consist of 2 elements: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D descriptive system comprised of following 5 dimensions: 1.Mobility, 2.Self-Care, 3.Usual Activities, 4.Pain/Discomfort and 5.Anxiety/Depression. Each of these 5 dimensions has 5 levels: 1: no problems; 2: slight problems; 3: moderate problems; 4: severe problems; 5: Unable to do. The digits for each of 5 dimensions were combined in a 5-digit number describing the participant's health state: e.g. state 11111 indicates no problem on any of the 5 dimensions. Index score was derived from the 5 dimensions scores using UK tariff. The weights based from the UK population was used for conversion, regardless of the origin country of participant. The score ranged from -0.594 (worst score) to 1.000 (best score). Baseline was last measurement done up to and including Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Day 0) and Day 29, 30, 57, 59, 64, 65, 85, 112, 113,163,169 and 373, Week 12 |
| Part B: Change From Baseline in FACIT-Fatigue Scores Over Time for Participants Who Received at Least One Dose of 100 mg OL Sirukumab in Part B | The FACIT-Fatigue is a 13-item questionnaire formatted for self-administration that assesses participant reported fatigue and its impact upon daily activities and function over the past seven days. Participants were asked to answer each question using a 5-point Likert-type scale (4 = Not at all; 3 = A little bit; 2 = Somewhat; 3 = Quite a bit; and 0 = Very Much) where 0 is a bad response and 4 is good response. Each of the 13 items of the FACIT-Fatigue Scale ranges from 0-4, with a range of possible total score from 0-52, 0 (Extreme fatigue) to 52 (No fatigue) where 0 being the worst possible score and 52 the best (i.e. less fatigue). Scores below 30 indicate severe fatigue. Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Day 0) and Day 85,87,91,113,162, 344,339,Week 12, 24 |
| Part B: Change From Baseline in FACIT-Fatigue Scores Over Time for Participants Who Never Received 100mg OL Sirukumab in Part B | The FACIT-Fatigue is a 13-item questionnaire formatted for self-administration that assesses participant reported fatigue and its impact upon daily activities and function over the past seven days. Participants were asked to answer each question using a 5-point Likert-type scale (4 = Not at all; 3 = A little bit; 2 = Somewhat; 3 = Quite a bit; and 0 = Very Much) where 0 is a bad response and 4 is good response. Each of the 13 items of the FACIT-Fatigue Scale ranges from 0-4, with a range of possible total score from 0-52, 0 (Extreme fatigue) to 52 (No fatigue) where 0 being the worst possible score and 52 the best (i.e. less fatigue). Scores below 30 indicate severe fatigue. Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Participants with post baseline data were reported. | Baseline (Day 0) and Day 85,87,91,113,162 344,339,Week 12, 24 |
| Part B: Change From Baseline in Pain NRS Scores Over Time for Participants Who Received at Least One Dose of 100 mg OL Sirukumab in Part B | The assessment of pain severity was made using a single pain severity item on which participants were asked to rate the severity of their average pain now on an 11-point numeric rating scale ranging from 0, no pain to 10, the worst pain imaginable. Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Day 0) and Day 85,87,91,113,162 344,339,Week 12, 24 |
| Part B: Change From Baseline in Pain NRS Scores Over Time for Participants Who Never Received at Least One Dose of 100mg OL Sirukumab in Part B | The assessment of pain severity was made using a single pain severity item on which participants were asked to rate the severity of their average pain now on an 11-point numeric rating scale ranging from 0, no pain to 10, the worst pain imaginable. Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Participants with post baseline data were reported. | Baseline (Day 0) and Day 85,87,91,113,162 344,339,Week 12, 24 |
| Part B: HAQDI Score Over Time for Participants Who Received at Least One Dose of 100 mg OL Sirukumab in Part B | Health Assessment Questionnaire-Disability Index (HAQ-DI) indicates the extent of participant's functional ability during the past week, and was assessed for subgroup of participants with symptoms of Polymyalgia Rheumatic (PMR). HAQ-DI included 20 questions in 8 categories of functioning - dressing and grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Each functional area contains at least two questions. For each question, there is a 4-level difficulty scale that is scored from 0 (minimum) to 3 (Maximum), representing no difficulty (0), some difficulty (1), much difficulty (2), and unable to do (3) where, lower score indicates less disability and higher scores indicates worse disability. Total score was calculated as average scores of 20 questions which can be interpreted in terms of 3 categories: from 0 to 1: mild difficulties to moderate disability, from 1 to 2: disability moderate to severe, from 2 to 3: severe to very severe disability | Day 87, 339, 344, Week 12, 24 |
| Part B: HAQDI Score Over Time for Participants Who Never Received 100 mg OL Sirukumab in Part B | Health Assessment Questionnaire-Disability Index (HAQ-DI) indicates the extent of participant's functional ability during the past week, and was assessed for subgroup of participants with symptoms of Polymyalgia Rheumatic (PMR). HAQ-DI included 20 questions in 8 categories of functioning - dressing and grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Each functional area contains at least two questions. For each question, there is a 4-level difficulty scale that is scored from 0 (minimum) to 3 (Maximum), representing no difficulty (0), some difficulty (1), much difficulty (2), and unable to do (3) where, lower score indicates less disability and higher scores indicates worse disability. Total score was calculated as average scores of 20 questions which can be interpreted in terms of 3 categories: from 0 to 1: mild difficulties to moderate disability, from 1 to 2: disability moderate to severe, from 2 to 3: severe to very severe disability | Day 29, 64, 65, 85, 112, 113, 169, 373 and Week 12 |
| Part B: Change From Baseline in PtGA Score for Participants Who Received at Least One Dose of 100 mg OL Sirukumab in Part B | The Patient's Global Assessments of Disease Activity was recorded on a Visual analog scale (VAS). of 10 centimeter (cm) ranging from 0 (very well) to 10 (very poor). Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Day 0), Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38, 40; Days 85, 87, 91, , 113, 162, 339, and 344 |
| Part B: Change From Baseline in PtGA Score for Participants Who Never Received 100 mg OL Sirukumab in Part B | The Patient's Global Assessments of Disease Activity was recorded on a Visual analog scale (VAS). of 10 centimeter (cm) ranging from 0 (very well) to 10 (very poor). Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Participants with post baseline data were reported. | Baseline (Day 0), Weeks 2, 4, 8, 12, 16, 36; Days 23, 29, 30, 57, 59, 64, 65, 85,112, 113, 115, 163, 169 and 373 |
| Part B: Change From Baseline in PhGA Score for Participants Who Received at Least One Dose of 100 mg OL Sirukumab in Part B | In PhGA was based on What is physician's assessment of the participant's current disease activity. PhGA used a 10 cm VAS ranging from 0 (none) to 10 (extremely active). Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Day 0) and Day 85, Day 113, Day 162, Day 203, Day 339, Day 344, Week 2, Week 4, Week 8, Week 12, Week 14, Week 16, Week 24, Week 36, Week 38, Week 40 |
| Part B: Change From Baseline in PhGA Score for Participants Who Never Received 100 mg OL Sirukumab in Part B | In PhGA was based on What is physician's assessment of the participant's current disease activity. PhGA used a 10 cm VAS ranging from 0 (none) to 10 (extremely active). Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Participants with post baseline data were reported. | Baseline (Day 0), Weeks 4, 8, 12, 16, 36; Days 23, 29, 30, 57, 59, 64, 65, 85, 112, 113, 163, 169 and 373 |
| Part B: Number of Participants With PGIC Score Over Time Who Received at Least One Dose of 100 mg OL Sirukumab in Part B | Patient-reported response to treatment was assessed using the PGIC measure, a single item completed by participant to provide a clinically meaningful summary of an individual's response to treatment. The assessment provides an estimate of the magnitude of treatment response at different time points during the study. Responses include: Much Better, Better, Slightly Better, No Change, Slightly Worse, Worse, and Much Worse. The categorical data of participant rating of change is summarized by treatment group, visit and response category. | Baseline (Day 1), Days 103 and 271 |
| Part B: Number of Participants With PGIC Score Over Time Who Never Received 100 mg OL Sirukumab in Part B | Patient-reported response to treatment was assessed using the PGIC measure, a single item completed by participant to provide a clinically meaningful summary of an individual's response to treatment. The assessment provides an estimate of the magnitude of treatment response at different time points during the study. Responses include: Much Better, Better, Slightly Better, No Change, Slightly Worse, Worse, and Much Worse. The categorical data of participant rating of change is summarized by treatment group, visit and response category. | Baseline (Day 1) |
| Part B: Change From Baseline in CRP Over Time for Participants Who Received at Least One Dose of 100 mg OL Sirukumab in Part B | Blood samples were collected for analysis of CRP. Data for Change from Baseline in serum CRP over time for part B was reported. Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Day 0), Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 |
| Part B: Change From Baseline in CRP Over Time for Participants Who Never Received 100 mg OL Sirukumab in Part B | Blood samples were collected for analysis of CRP. Data for Change from Baseline in serum CRP over time for part B was reported. Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Day 0), Weeks 4, 8, 12, 16, 24 and 36 |
| Part B: Change From Baseline in ESR Over Time for Participants Who Received at Least One Dose of 100 mg OL Sirukumab in Part B | Blood samples were collected for analysis of ESR. Data for Change from Baseline in ESR over time for part A was reported. Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Day 0), Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 |
| Part B: Change From Baseline in ESR Over Time for Participants Who Never Received 100 mg OL Sirukumab in Part B | Blood samples were collected for analysis of ESR. Data for Change from Baseline in ESR over time for part A was reported. Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Day 0), Weeks 4, 8, 12, 16, 24 and 36 |
| Part B: Change From Baseline in EQ-5D-5L VAS Over Time for Participants Who Received at Least One Dose of 100 mg OL Sirukumab in Part B | EQ-5D essentially consists of 2 elements: the EQ-5D descriptive system and the EQ VAS. The EQ-5D descriptive system comprised of the following 6 dimensions: 1.Mobility, 2.Self, 3.Usual Activities, 4.Pain/Discomfort, 5.Anxiety/Depression; 6.How good or or bad your health is today. Each of these 6 dimensions has 5 levels: 1: no problems; 2: slight problems; 3: moderate problems; 4: severe problems; 5: Unable to do. The EQ VAS records the respondent's self-rated health on a vertical line, VAS where the endpoints are 'Best imaginable health state' and 'Worst imaginable health state'. Answers to 'How good or bad your health is today' were measured on a 100 point VAS scale. Baseline for Part B is the last non-missing measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Day 0) and Days 85, 87, 91, 113, 162, 339 and 344 and Weeks 12 and 24 |
| Part B: Change From Baseline in EQ-5D-5L VAS Over Time for Participants Who Never Received 100 mg OL Sirukumab in Part B | EQ-5D essentially consists of 2 elements: the EQ-5D descriptive system and the EQ VAS. The EQ-5D descriptive system comprised of the following 6 dimensions: 1.Mobility, 2.Self, 3.Usual Activities, 4.Pain/Discomfort, 5.Anxiety/Depression; 6.How good or or bad your health is today. Each of these 6 dimensions has 5 levels: 1: no problems; 2: slight problems; 3: moderate problems; 4: severe problems; 5: Unable to do. The EQ VAS records the respondent's self-rated health on a vertical line, VAS where the endpoints are 100 (Best imaginable health state) and 0 (Worst imaginable health state). Answers to 'How good or bad your health is today' were measured on a 100 point VAS scale. Baseline for Part B is the last non-missing measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Day 0) and Days 23, 29, 30, 57, 59, 64, 65, 85, 112, 113, 163, 169, 344 and 373 and Week 12 |
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Giant Cell Arteritis, Sirukumab, Prednisone
|
Prednisone, Antibodies, Monoclonal, Anti-Inflammatory Agents, Glucocorticoids, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Physiological Effects of Drugs, Antineoplastic Agents, Hormonal, Antineoplastic Agents, Immunologic Factors
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: Sirukumab, Dose 1+prednisone (6-month taper)<br>Subjects will receive blinded sirukumab 100 mg subcutaneously (SC) every 2 weeks (q2w) for 52 weeks plus a pre-specified maximum of 6-month oral prednisone taper regimen. | Drug: Sirukumab<br>* Sirukumab will be provided as 1 millilitre (mL) Pre-filled Syringe (PFS), containing 100 mg/mL or 50 mg/mL of sirukuma, fitted with a spring-powered, disposable autoinjector device for single use SC administration of liquid biologic drug.<br>Drug: Prednisone<br>* Prednisone will be provided as tablets with dosage level up to-60 mg/day. The prednisone dose for all subjects will be determined by the Investigator and starting doses will be within 20-60 mg prednisone at Baseline (Randomization).<br>Drug: Placebo to match prednisone<br>* Placebo to match prednisone will be provided as tablets.<br>|
| Experimental: Part A: Sirukumab, Dose 1+prednisone (3-month taper)<br>Subjects will receive blinded sirukumab 100 mg SC q2w for 52 weeks plus a pre-specified maximum of 3-month oral prednisone taper regimen. | Drug: Sirukumab<br>* Sirukumab will be provided as 1 millilitre (mL) Pre-filled Syringe (PFS), containing 100 mg/mL or 50 mg/mL of sirukuma, fitted with a spring-powered, disposable autoinjector device for single use SC administration of liquid biologic drug.<br>Drug: Prednisone<br>* Prednisone will be provided as tablets with dosage level up to-60 mg/day. The prednisone dose for all subjects will be determined by the Investigator and starting doses will be within 20-60 mg prednisone at Baseline (Randomization).<br>Drug: Placebo to match prednisone<br>* Placebo to match prednisone will be provided as tablets.<br>|
| Experimental: Part A: Sirukumab, Dose 2+prednisone (6-month taper)<br>Subjects will receive blinded sirukumab 50 mg SC every 4 weeks (q4w) for 52 weeks plus a pre-specified maximum of 6-month oral prednisone taper regimen. | Drug: Sirukumab<br>* Sirukumab will be provided as 1 millilitre (mL) Pre-filled Syringe (PFS), containing 100 mg/mL or 50 mg/mL of sirukuma, fitted with a spring-powered, disposable autoinjector device for single use SC administration of liquid biologic drug.<br>Drug: Prednisone<br>* Prednisone will be provided as tablets with dosage level up to-60 mg/day. The prednisone dose for all subjects will be determined by the Investigator and starting doses will be within 20-60 mg prednisone at Baseline (Randomization).<br>Drug: Placebo to match prednisone<br>* Placebo to match prednisone will be provided as tablets.<br>|
| Placebo Comparator: Part A:Placebo to match sirutkumab+prednisone (6-month taper)<br>Subjects will receive blinded placebo to match sirutkumab q2w for 52 weeks plus a pre-specified maximum of 6-month oral prednisone taper regimen. | Drug: Placebo to match sirukumab<br>* Placebo to match sirukumab will be provided as 1.0 mL PFS fitted with a spring-powered, disposable autoinjector device for single use SC administration of liquid biologic drug.<br>Drug: Prednisone<br>* Prednisone will be provided as tablets with dosage level up to-60 mg/day. The prednisone dose for all subjects will be determined by the Investigator and starting doses will be within 20-60 mg prednisone at Baseline (Randomization).<br>Drug: Placebo to match prednisone<br>* Placebo to match prednisone will be provided as tablets.<br>|
| Placebo Comparator: Part A:Placebo to match sirukumab+prednisone (12-month taper)<br>Subjects will receive blinded placebo to match sirutkumab q2w for 52 weeks plus a pre-specified maximum of 12-month oral prednisone taper regimen. | Drug: Placebo to match sirukumab<br>* Placebo to match sirukumab will be provided as 1.0 mL PFS fitted with a spring-powered, disposable autoinjector device for single use SC administration of liquid biologic drug.<br>Drug: Prednisone<br>* Prednisone will be provided as tablets with dosage level up to-60 mg/day. The prednisone dose for all subjects will be determined by the Investigator and starting doses will be within 20-60 mg prednisone at Baseline (Randomization).<br>Drug: Placebo to match prednisone<br>* Placebo to match prednisone will be provided as tablets.<br>|
| Experimental: Part B:Open-label sirukumab 100 mg SC (if applicable)<br>Subjects completing Part A will receive open label 100 mg SC q2w for a maximum of 52 weeks based on remission status and disease activity at the primary 52-week endpoint or prednisone tapering status of subject during Part A. Methotrexate will be provided to subjects, alone or in addition to sirukumab treatment during Part B, based on the discretion of the investigator. | Drug: Sirukumab<br>* Sirukumab will be provided as 1 millilitre (mL) Pre-filled Syringe (PFS), containing 100 mg/mL or 50 mg/mL of sirukuma, fitted with a spring-powered, disposable autoinjector device for single use SC administration of liquid biologic drug.<br>|
|
Efficacy and Safety Study of Sirukumab in Patients With Giant Cell Arteritis
Study Overview
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Brief Summary
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Sirukumab is a fully human anti-interleukin-6 (IL-6) immunoglobulin G1-kappa with a high affinity and specificity for binding to the human IL-6 molecule that may have therapeutic benefit in the treatment of giant cell arteritis (GCA) by interruption of multiple pathogenic pathways. Sirukumab inhibits IL-6-mediated signal transducer and activator of transcription 3 (STAT3) phosphorylation, resulting in the inhibition of the biological effect of IL-6. This study will evaluate the efficacy and safety of sirukumab to characterize the benefit-to-risk profile of sirukumab in the treatment of active GCA. The study will be conducted in 2 distinct parts (Part A and Part B) and consists of the following phases: Screening phase, Part A: 52-week double-blind treatment phase, Part B: 104-week extension phase with the option to receive open-label sirukumab based on disease status and a 16-week follow-up phase if applicable. Approximately 204 subjects with a diagnosis of GCA and active disease within 6 weeks of baseline will be randomized into Part A, the 52-week double-blind treatment phase, to receive one of two doses of sirukumab or placebo, each in addition to a pre-specified prednisone taper. The efficacy and safety of sirukumab in sustaining remission will be assessed at Week 52. Subjects completing Part A of the study will be eligible to enter Part B, the 104-week extension phase, designed to investigate the long-term maintenance of remission and safety following cessation of sirukumab treatment and to assess long-term corticosteroid use. Subjects with active GCA at the end of Part A or those with new onset of GCA flare during the first 52 weeks of Part B will be eligible to receive open-label sirukumab. Subjects will need to have follow-up safety evaluations for at least 16 weeks after receiving the last dose of study drug, applicable only for those who are withdrawn prematurely from the study or whose open-label sirukumab treatment in Part B completes after Week 88.
Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Sirukumab in the Treatment of Patients With Giant Cell Arteritis
Conditions
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Giant Cell Arteritis
Intervention / Treatment
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* Drug: Sirukumab
* Drug: Placebo to match sirukumab
* Drug: Prednisone
* Drug: Placebo to match prednisone
Participation Criteria
=================
Eligibility Criteria
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Inclusion Criteria: Diagnosis of GCA defined by the following Revised GCA Diagnosis Criteria: Age >=50 years. History of ESR >=50 millimeter/hour (mm/hour) or CRP >=2.45 milligram/deciliter(mg/dL). Presence of at least one of the following: Unequivocal cranial symptoms of GCA; Unequivocal symptoms of polymyalgia rheumatic (PMR). Presence of at least one of the following: Temporal artery biopsy revealing features of GCA; Evidence of large-vessel vasculitis by angiography or cross-sectional imaging. Active GCA within 6 weeks of Randomization (Baseline) where active disease is defined by an ESR >=30 mm/hr or CRP >=1 mg/dL AND the presence of at least one of the following: Unequivocal cranial symptoms of GCA; Unequivocal symptoms of PMR; Other features judged by the clinician investigator to be consistent with GCA or PMR flares. At screening, receiving or able to receive prednisone 20-60 mg/day for the treatment of active GCA. Clinically stable GCA disease at baseline such that the subject is able to safely participate in the blinded prednisone taper regimen in the opinion of the investigator. Practicing acceptable methods of birth control if a female of child-bearing potential. No evidence of active or latent infection with Mycobacterium tuberculosis (TB). Exclusion Criteria: Are pregnant or breastfeeding. Recent (within the past 12 weeks) or planned major surgery that would impact on study procedures or assessments. Organ transplantation recipients (except corneas within 3 months prior to baseline visit). Had prior treatment with any of the following: Systemic immunosuppressives) within 4 weeks of baseline; Biologic agents targeted at reducing tumor necrosis factor-alpha (TNF-alpha) within 2-8 weeks of baseline, depending on the agent; Any prior use of tocilizumab or other anti-IL-6 agents; B-cell depleting agents (eg, rituximab) within 12 months prior to baseline or longer if B cell counts have not returned to normal range or baseline levels; Cytotoxic drugs such as cyclophosphamide, chlorambucil, nitrogen mustard, or other alkylating agents within 4 weeks of baseline; Abatacept within 8 weeks of baseline; Tofacitinib within 4 weeks of baseline; Methotrexate use within 2 weeks of baseline. Methylprednisolone > 100 mg/day intravenous (IV) (or equivalent) within 8 weeks of baseline. History of severe allergic reactions to monoclonal antibodies, human proteins, or excipients. Evidence of serious concomitant disease, which in the opinion of the investigator makes them unsuitable for participation in the study. Major ischemic event, unrelated to GCA, within 12 weeks of screening. Marked baseline prolongation of corrected QT (QTc) interval >= 450 milliseconds (msec) (QTc by Bazett's formula [QTcB ]or QTc by Fridericia's formula [QTcF] ), history of Torsade de Pointes, family history of long QT syndrome, history of second or third degree heart block. Current liver disease that could interfere with the trial History of or current active diverticulitis, inflammatory bowel disease, or other symptomatic gastrointestinal tract condition that might predispose to bowel perforation. History of known demyelinating diseases such as multiple sclerosis or optic neuritis. Active infections, or history of recurrent infections or have required management of acute or chronic infections, as follows: Currently on any suppressive therapy for a chronic infection, history or suspicion of chronic infection, hospitalization for treatment of infection within 60 days of the baseline visit, or use of parenteral (IV) or intra-muscular [IM]) antimicrobials within 60 days of baseline or oral antimicrobials within 30 days of baseline Primary or secondary immunodeficiency or any other autoimmune disease. Human immunodeficiency virus (HIV) infection, hepatitis C or hepatitis B infection Live virus or bacterial vaccination within 3 months before the first administration of study drug
Ages Eligible for Study
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Minimum Age: 50 Years
Sexes Eligible for Study
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All
Accepts Healthy Volunteers
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No
Study Plan
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How is the study designed?
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Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: Sirukumab, Dose 1+prednisone (6-month taper)<br>Subjects will receive blinded sirukumab 100 mg subcutaneously (SC) every 2 weeks (q2w) for 52 weeks plus a pre-specified maximum of 6-month oral prednisone taper regimen. | Drug: Sirukumab<br>* Sirukumab will be provided as 1 millilitre (mL) Pre-filled Syringe (PFS), containing 100 mg/mL or 50 mg/mL of sirukuma, fitted with a spring-powered, disposable autoinjector device for single use SC administration of liquid biologic drug.<br>Drug: Prednisone<br>* Prednisone will be provided as tablets with dosage level up to-60 mg/day. The prednisone dose for all subjects will be determined by the Investigator and starting doses will be within 20-60 mg prednisone at Baseline (Randomization).<br>Drug: Placebo to match prednisone<br>* Placebo to match prednisone will be provided as tablets.<br>|
| Experimental: Part A: Sirukumab, Dose 1+prednisone (3-month taper)<br>Subjects will receive blinded sirukumab 100 mg SC q2w for 52 weeks plus a pre-specified maximum of 3-month oral prednisone taper regimen. | Drug: Sirukumab<br>* Sirukumab will be provided as 1 millilitre (mL) Pre-filled Syringe (PFS), containing 100 mg/mL or 50 mg/mL of sirukuma, fitted with a spring-powered, disposable autoinjector device for single use SC administration of liquid biologic drug.<br>Drug: Prednisone<br>* Prednisone will be provided as tablets with dosage level up to-60 mg/day. The prednisone dose for all subjects will be determined by the Investigator and starting doses will be within 20-60 mg prednisone at Baseline (Randomization).<br>Drug: Placebo to match prednisone<br>* Placebo to match prednisone will be provided as tablets.<br>|
| Experimental: Part A: Sirukumab, Dose 2+prednisone (6-month taper)<br>Subjects will receive blinded sirukumab 50 mg SC every 4 weeks (q4w) for 52 weeks plus a pre-specified maximum of 6-month oral prednisone taper regimen. | Drug: Sirukumab<br>* Sirukumab will be provided as 1 millilitre (mL) Pre-filled Syringe (PFS), containing 100 mg/mL or 50 mg/mL of sirukuma, fitted with a spring-powered, disposable autoinjector device for single use SC administration of liquid biologic drug.<br>Drug: Prednisone<br>* Prednisone will be provided as tablets with dosage level up to-60 mg/day. The prednisone dose for all subjects will be determined by the Investigator and starting doses will be within 20-60 mg prednisone at Baseline (Randomization).<br>Drug: Placebo to match prednisone<br>* Placebo to match prednisone will be provided as tablets.<br>|
| Placebo Comparator: Part A:Placebo to match sirutkumab+prednisone (6-month taper)<br>Subjects will receive blinded placebo to match sirutkumab q2w for 52 weeks plus a pre-specified maximum of 6-month oral prednisone taper regimen. | Drug: Placebo to match sirukumab<br>* Placebo to match sirukumab will be provided as 1.0 mL PFS fitted with a spring-powered, disposable autoinjector device for single use SC administration of liquid biologic drug.<br>Drug: Prednisone<br>* Prednisone will be provided as tablets with dosage level up to-60 mg/day. The prednisone dose for all subjects will be determined by the Investigator and starting doses will be within 20-60 mg prednisone at Baseline (Randomization).<br>Drug: Placebo to match prednisone<br>* Placebo to match prednisone will be provided as tablets.<br>|
| Placebo Comparator: Part A:Placebo to match sirukumab+prednisone (12-month taper)<br>Subjects will receive blinded placebo to match sirutkumab q2w for 52 weeks plus a pre-specified maximum of 12-month oral prednisone taper regimen. | Drug: Placebo to match sirukumab<br>* Placebo to match sirukumab will be provided as 1.0 mL PFS fitted with a spring-powered, disposable autoinjector device for single use SC administration of liquid biologic drug.<br>Drug: Prednisone<br>* Prednisone will be provided as tablets with dosage level up to-60 mg/day. The prednisone dose for all subjects will be determined by the Investigator and starting doses will be within 20-60 mg prednisone at Baseline (Randomization).<br>Drug: Placebo to match prednisone<br>* Placebo to match prednisone will be provided as tablets.<br>|
| Experimental: Part B:Open-label sirukumab 100 mg SC (if applicable)<br>Subjects completing Part A will receive open label 100 mg SC q2w for a maximum of 52 weeks based on remission status and disease activity at the primary 52-week endpoint or prednisone tapering status of subject during Part A. Methotrexate will be provided to subjects, alone or in addition to sirukumab treatment during Part B, based on the discretion of the investigator. | Drug: Sirukumab<br>* Sirukumab will be provided as 1 millilitre (mL) Pre-filled Syringe (PFS), containing 100 mg/mL or 50 mg/mL of sirukuma, fitted with a spring-powered, disposable autoinjector device for single use SC administration of liquid biologic drug.<br>|
What is the study measuring?
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Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Number of Participants in Sustained Remission at Week 52 | Sustained remission was defined as having achieved all of the following: 1) remission at Week 12, 2) absence of disease flare Week 12 through Week 52, 3) completion of the assigned prednisone taper, and 4) no requirement for rescue therapy through Week 52. Remission was defined as absence of clinical signs and symptoms of GCA and normalization of erythrocyte sedimentation rate (ESR) [<30 millimeters per hour] and C-reactive Protein (CRP) [<1 milligram/deciliter]) and flare was defined as recurrence of symptoms attributable to active GCA, with or without elevations in ESR and/or CRP. Data for number of participants in sustained remission at Week 52 is presented. Only those participants who completed Week 52 visit or withdrew before 10 Oct 2017 were included in the analysis. | Week 52 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part B: Number of Participants Who Remained in Sustained Remission Without Requirement for Rescue Therapy or Treatment Change at Week 24 | Participants who remained in sustained remission without requirement for rescue therapy or treatment change at each scheduled visit of Part B were defined as participants having achieved all of the following criteria: 1. Participants in sustained remission at the Week 52 visit of Part A, 2. Absence of disease flare, 3. No requirement for rescue therapy at any time through Week 24 of Part B, 4. No requirement for treatment change at any time through Week 24 of Part B. Remission was defined as absence of clinical signs and symptoms of GCA and normalization of ESR [<30 millimeters per hour] and CRP [<1 milligram/deciliter]) and flare was defined as recurrence of symptoms attributable to active GCA, with or without elevations in ESR and/or CRP. | Week 24 |
| Part A: Cumulative Prednisone Dose Over Time | Cumulative prednisone is the dose from the taper (both open-label and blinded) as well as from the corticosteroid rescue therapies. Cumulative dose at the specified Week was derived as the sum of all the doses from Baseline to the specified Week at each visit was calculated based on the number of participants who attended that visit. For the main analysis of cumulative prednisone dose over time. Data for Prednisone Dose- Study Drug and Prednisone Equivalent Concomitant Therapy for part A is presented. ITT population and the number of participants included at specific time points were based on the participants who attended a scheduled or unscheduled visit mapped to that time point and received a total prednisone dose greater than 0 mg. | Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 |
| Part B: Number of Participants in Sustained Remission Over Time | Sustained remission was defined as having achieved all of the following: 1) remission at Week 12 (absence of signs and symptoms of GCA and normalization of ESR and CRP), 2) absence of disease flare Week 12 through Week 52 with or without elevations in ESR and/or CRP, 3) completion of the assigned prednisone taper, and 4) no requirement for rescue therapy through Week 52. Remission was defined as absence of clinical signs and symptoms of GCA and normalization of ESR [<30millimeters per hour] and CRP [<1milligram/deciliter]) and Flare was defined as recurrence of symptoms attributable to active GCA, with or without elevations in ESR and/or CRP. Data for number of participants in sustained remission over time for Part B is presented. Only participants who were in sustained remission at Week 52 of Part A, who Completed the Week X Visit of Part B or who Withdraw before 10th of October 2017 were included in the analysis. | Weeks 4, 8 and 12 |
| Part A: Time to First Disease Flare After Clinical Remission | Clinical remission was defined as absence of clinical signs and symptoms of GCA, which was determined by a lack of flare for the participant. If a participant had a flare, they had one or more signs and symptoms, and therefore are not considered as being in clinical remission. Time to first disease flare (days) was calculated as (Date of First Flare - Date of Clinical Remission + 1 day). Data for Time to first disease flare after clinical remission for part A is presented. | Week 52 |
| Part B: Time to First Disease Flare for Participants in Sustained Remission | Clinical remission was defined as absence of clinical signs and symptoms of GCA. If a participant had a flare, they had one or more signs and symptoms, and therefore are not considered as being in clinical remission. Time to event (days) is defined as the duration in days from the date of the Week 52 visit of Part A to the start date of Event (Date of First Flare - Date of Week 52 visit of Part A + 1). Data for Time to first disease flare after clinical remission for part B is presented. | Week 52 |
| Part A: Number of Disease Flares Over Time | This summarizes disease flares over time with no adjustment for exposure to study drugs, calculated by taking the last visit before a participant withdrew and then counting the number of participants with at least 1 flare up to that point and summing up the total number of flares experienced by each of these participants; participants who did not reach Week 2 were not included in this analysis. Data for number of disease flares per participant over time for part A were presented. | Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 |
| Part A: Number of Participants With at Least One Hospitalization for Disease Flare | Number of participants with at least one hospitalization for disease flare at a given visit is the number of participants with at least one hospitalization for disease flare between first SC IP intake and the day of the given visit. Data for participants requiring at least one hospitalization for disease flare for part A is presented. | Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 |
| Part A: Number of Hospitalizations for Disease Flare Over Time | Number of hospitalizations for disease flare at given visit is the number of hospitalizations for disease flare between first SC IP intake and the day of the of the given visit.. Data for number of hospitalizations for disease flare over time for part A was presented. | Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 |
| Part A: Mean 36-item Short Form Health Survey Version 2 (SF-36 v2) Acute Score Over Time | SF-36v2 acute health survey questionnaire consists of the following 8 multi-item scales: 1. Limitations in physical functioning due to health problems, 2. Limitations in usual role activities due to physical health problems, 3. Bodily pain, 4. General mental health (psychological distress and well-being), 5. Limitations in usual role activities due to personal or emotional problems, 6. Limitations in social functioning due to physical or mental health problems. 7. Vitality (energy and fatigue) and 8. General health perception. These 8 scales were scored from 0 to 100, 0 (worst score) to 100 (best score) where higher scores indicates better health. Data for Physical Component Summary (PCS), Mental Component Summary (MCS) scores was presented. | Baseline (Week 0), Weeks 12, 24, 36, 52 |
| Part A: Mean EuroQol - 5 Dimensions, 5 Levels (EQ-5D-5L) Index Score Over Time | EuroQoL-5 Dimensions consist of 2 elements: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D descriptive system comprised of following 5 dimensions: 1.Mobility, 2.Self-Care, 3.Usual Activities, 4.Pain/Discomfort and 5.Anxiety/Depression. Each of these 5 dimensions has 5 levels: 1: no problems; 2: slight problems; 3: moderate problems; 4: severe problems; 5: Unable to do. The digits for each of 5 dimensions were combined in a 5-digit number describing the participant's health state: e.g. state 11111 indicates no problem on any of the 5 dimensions. Index score was derived from the 5 dimensions scores using UK tariff. The weights based from the UK population was used for conversion, regardless of the origin country of participant. The score ranged from -0.594 (worst score) to 1.000 (best score). | Baseline (Week 0) and Weeks 12, 24, 36, 52 |
| Part A: Mean EQ-5D-5L Visual Analogue Scale (VAS) Over Time | EQ-5D essentially consists of 2 elements: the EQ-5D descriptive system and the EQ VAS. The EQ-5D descriptive system comprised of the following 5 dimensions: 1.Mobility, 2.Self-Care, 3.Usual Activities, 4.Pain/Discomfort and 5.Anxiety/Depression. Each of these 5 dimensions has 5 levels: 1: no problems; 2: slight problems; 3: moderate problems; 4: severe problems; 5: Unable to do. The digits for each of the 5 dimensions were combined in a 5-digit number describing the participant's health state: e.g. state 11111 indicates no problem on any of the 5 dimensions. The index score was derived from the 5 dimensions scores using UK tariff. The weights based from the UK population was used for the conversion, regardless of the origin country of participant. The score ranged from -0.594 (worst score) to 1 (best score). The EQ VAS records the respondent's self-rated health on a vertical line, VAS where the endpoints are 'Best imaginable health state' and 'Worst imaginable health state'. | Baseline (Week 0) and Weeks 12, 24, 36, 52 |
| Part A: Mean Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-Fatigue) Scores Over Time | The FACIT-Fatigue is a 13-item questionnaire formatted for self-administration that assesses participant reported fatigue and its impact upon daily activities and function over the past seven days. Participants were asked to answer each question using a 5-point Likert-type scale (4 = Not at all; 3 = A little bit; 2 = Somewhat; 3 = Quite a bit; and 0 = Very Much) where 0 is a bad response and 4 is good response. Each of the 13 items of the FACIT-Fatigue Scale ranges from 0-4, with a range of possible total score from 0-52, 0 (Extreme fatigue) to 52 (No fatigue) where 0 being the worst possible score and 52 the best (i.e. less fatigue). Scores below 30 indicate severe fatigue. Each negatively-worded item response was recoded so that 0 is a bad response and 4 is good response. All responses were added with equal weight to obtain the total score. The total score was calculated as the sum of all the individual items after recoding some of the items. | Baseline (Week 0), Weeks 12, 24, 36, 52 |
| Part A: Mean Pain Numeric Rating Scale (NRS) Scores Over Time | The assessment of pain severity was made using a single pain severity item on which participants were asked to rate the severity of their average pain on a 11-point numeric rating scale ranging from 0, no pain to 10, the worst pain imaginable. Data for NRS scores over time for part A is reported. | Baseline (Week 0), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 |
| Part A: Mean Health Assessment Questionnaire - Disability Index (HAQDI) Score Over Time | Health Assessment Questionnaire-Disability Index (HAQ-DI) indicates the extent of participant's functional ability during the past week, and was assessed for subgroup of participants with symptoms of Polymyalgia Rheumatic (PMR). HAQ-DI included 20 questions in 8 categories of functioning - dressing and grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Each functional area contains at least two questions. For each question, there is a 4-level difficulty scale that is scored from 0 (minimum) to 3 (Maximum), representing no difficulty (0), some difficulty (1), much difficulty (2), and unable to do (3) where, lower score indicates less disability and higher scores indicates worse disability. Total score was calculated as average scores of 20 questions which can be interpreted in terms of 3 categories: from 0 to 1: mild difficulties to moderate disability, from 1 to 2: disability moderate to severe, from 2 to 3: severe to very severe disability. | Baseline (Week 0) and Weeks 12, 24, 36 and 52 |
| Part A: Number of Participants With Patient Global Impression of Change (PGIC) Score Over Time | Patient-reported response to treatment was assessed using the PGIC measure, a single item completed by participant to provide a clinically meaningful summary of an individual's response to treatment. The assessment provides an estimate of the magnitude of treatment response at different time points during the study. Responses include: Much Better, Better, Slightly Better, No Change, Slightly Worse, Worse, and Much Worse. The categorical data of participant rating of change is summarized by treatment group, visit and response category. | Weeks 12, 24 and 52 |
| Part A: Mean Patient Global Assessment of Disease Activity (PtGA) Score Over Time | The Patient's Global Assessments of Disease Activity was recorded on a Visual analog scale (VAS) of 10 centimeter (cm) ranging from 0 (very well) to 10 (very poor). | Baseline (Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 |
| Part A: Mean Physician Global Assessment of Disease Activity (PhGA) Score Over Time | The Physician's Global Assessments of Disease Activity was recorded on a VAS of 10 cm ranging from 0 (none) to 10 (extremely active). | Baseline (Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 |
| Part A: Change From Baseline in Serum C Reactive Protein (CRP) Over Time | Blood samples were collected for analysis of CRP. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for Change from Baseline in serum CRP over time for part A was reported. The Safety set comprised of all randomized participants who received at least 1 dose of SC IP. | Baseline (Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 |
| Part A: Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Over Time | Blood samples were collected for analysis of ESR. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for Change from Baseline in ESR over time for part A was reported. | Baseline (Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 |
| Part A: Number of Participants With Adverse Events (AEs), Serious AEs (SAEs) and Corticosteroid Related AEs | An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinaemia were categorized as SAE. Number of participants with AEs, SAEs and corticosteroid related AEs have been reported. | Up to 52 weeks |
| Part A: Change From Baseline in : Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP and DBP were measured in semi-supine position after 5 minutes rest at indicated time points. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Week 0), Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 |
| Part A: Change From Baseline in Pulse Rate | Pulse rate was measured in semi-supine position after 5 minutes rest at Baseline and up to 52 weeks. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Week 0) and Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 |
| Part A: Change From Baseline in Temperature | Temperature was measured in semi-supine position after 5 minutes rest at Baseline and up to 52 weeks. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Week 0) and Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 |
| Part A: Change From Baseline in Hematology Parameters- Eosinophils, Leukocytes, Lymphocytes, Neutrophils and Platelets | Blood samples were collected to analyze the hematology parameters including Eosinophils, Leukocytes, Lymphocytes, Neutrophils and Platelets. Change from Baseline is presented for these parameters. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Week 0) and Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 |
| Part A: Change From Baseline in Hematology Parameters- Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin | Blood samples were collected to analyze the hematology parameters including MCHC and Hemoglobin. Change from Baseline is presented for these parameters. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Week 0) and Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 |
| Part A: Change From Baseline in Hematology Parameter-Hematocrit | Blood samples were collected to analyze the hematology parameter Hematocrit. Change from Baseline is presented for this parameter. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Week 0) and Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 |
| Part A: Change From Baseline in Hematology Parameter -Erythrocytes Mean Corpuscular Volume | Blood samples were collected to analyze the hematology parameter Erythrocytes Mean Corpuscular Volume. Change from Baseline is presented for this parameter. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Week 0) and Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 |
| Part A:Change From Baseline in Hematology Parameter-Erythrocytes Mean Corpuscular Hemoglobin | Blood samples were collected to analyze the hematology parameter Erythrocytes Mean Corpuscular Hemoglobin. Change from Baseline is presented for this parameter. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Week 0) and Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 |
| Part A:Change From Baseline in Hematology Parameter- Erythrocytes | Blood samples were collected to analyze the hematology parameter Erythrocytes. Change from Baseline is presented for this parameter. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Week 0) and Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 |
| Part A: Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide, Chloride, Glucose, Phosphate, Potassium, Sodium and Urea | Blood samples were collected to analyze the chemistry parameters including Calcium, Carbon Dioxide, Chloride, Glucose, Phosphate, Potassium, Sodium and Urea . Change from Baseline is presented for these parameters. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Week 0) and Weeks 2, 4 ,8,12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 |
| Part A: Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein | Blood samples were collected to analyze the chemistry parameters including Albumin and Protein. Change from Baseline is presented for these parameters. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 |
| Part A: Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST) | Blood samples were collected to analyze the chemistry parameters including ALT,ALP and AST. Change from Baseline is presented for these parameters. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 |
| Part A: Change From Baseline in Clinical Chemistry Parameters: Bilirubin, Creatinine, Direct Bilirubin and Indirect Bilirubin | Blood samples were collected to analyze the chemistry parameters including bilirubin, creatinine, direct bilirubin and indirect bilirubin. Baseline was defined as the last non-missing value before first SC IP intake. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 |
| Part A: Mean Serum Concentrations of Sirukumab | Blood samples for Pharmacokinetic analysis of sirukumab serum concentrations were planned to be collected at specified time points. | Baseline (Week 0), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 44 and 52 |
| Part A: Mean Serum Anti-sirukumab Antibodies | Blood samples for Pharmacokinetic analysis of Serum anti-sirukumab antibodies were planned to be collected at specified time points. | Baseline (Week 0) and up to 52 weeks |
| Part A: Change From Baseline in Free and Total Interleukin-6 (IL-6) Over Time | Blood samples for Pharmacodynamic analysis were planned but not collected due to early termination of study. | Baseline (Week 0) and up to 52 weeks |
| Part B: Number of Participants With AEs, SAEs and Corticosteroid Related AEs Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B | An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinaemia were categorized as SAE. Number of participants with AEs, SAEs and corticosteroid related AEs for part B have been reported. | Up to 120 weeks |
| Part B: Number of Participants With AEs, SAEs and Corticosteroid Related AEs Who Never Received 100mg OL Sirukumab in Part B | An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinaemia were categorized as SAE. Number of participants with AEs, SAEs and corticosteroid related AEs for part B have been reported. | Up to 120 weeks |
| Part B: Change From Baseline in SBP and DBP for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B | SBP and DBP were measured in semi-supine position after 5 minutes rest for the participant. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented. | Baseline (Week 0) and Weeks 2,4,8,12,14,16,24,36,38,40 and follow up (Week 120) |
| Part B: Change From Baseline in SBP and DBP for Participants Who Never Received 100 mg Open Label Sirukumab in Part B | SBP and DBP were measured in semi-supine position after 5 minutes rest for the participant. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented. | Baseline (Week 0) and Weeks 4,8,12,16,24,36 and follow up (Week 120) |
| Part B: Change From Baseline in Pulse Rate for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B | Pulse rate was measured in semi-supine position after 5 minutes rest. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented. | Baseline (Week 0) and Weeks 2,4,8,12,14,16,24,36,38,40 and follow up (Week 120) |
| Part B: Change From Baseline in Pulse Rate for Participants Who Never Received 100 mg Open Label Sirukumab in Part B | Pulse rate was measured in semi-supine position after 5 minutes rest. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab is presented. | Baseline (Week 0) and Weeks 4,8,12,16,24,36 and follow up (Week 120) |
| Part B: Change From Baseline in Temperature for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B | Temperature was measured in semi-supine position after 5 minutes rest.. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented. | Baseline (Week 0) and Weeks 2,4,8,12,14,16,24,36,38,40 and follow up (Week 120) |
| Part B: Change From Baseline in Temperature for Participants Who Never Received 100 mg Open Label Sirukumab in Part B | Temperature was measured in semi-supine position after 5 minutes rest.. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented. | Baseline (Week 0) and Weeks 4,8,12,16,24,36 and follow up (Week 120) |
| Part B: Change From Baseline in Hematology Parameters- Eosinophils, Leukocytes, Lymphocytes, Neutrophils and Platelets for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B | Blood samples were collected to analyze the hematology parameters including Eosinophils, Leukocytes, Lymphocytes, Neutrophils and Platelets. Change from Baseline is presented for these parameters.Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented. | Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 |
| Part B: Change From Baseline in Hematology Parameters- Eosinophils, Leukocytes, Lymphocytes, Neutrophils and Platelets for Participants Who Never Received 100 mg Open Label Sirukumab in Part B | Blood samples were collected to analyze the hematology parameters including Eosinophils, Leukocytes, Lymphocytes, Neutrophils and Platelets. Change from Baseline is presented for these parameters.Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented. | Baseline (Week 0) and Weeks 4,8,12,16,24 and 36 |
| Part B: Change From Baseline in Hematology Parameters- MCHC and Hemoglobin for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B | Blood samples were collected to analyze the hematology parameters including MCHC and Hemoglobin. Change from Baseline is presented for these parameters. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented. | Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 |
| Part B: Change From Baseline in Hematology Parameters- MCHC and Hemoglobin for Participants Who Never Received 100 mg Open Label Sirukumab in Part B | Blood samples were collected to analyze the hematology parameters including MCHC and Hemoglobin. Change from Baseline is presented for these parameters. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented. | Baseline (Week 0) and Weeks 4,8,12,16,24 and 36 |
| Part B: Change From Baseline in Hematology Parameter-Hematocrit for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B | Blood samples were collected to analyze the hematology parameter Hematocrit. Change from Baseline is presented for this parameter. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented. | Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 |
| Part B: Change From Baseline in Hematology Parameter-Hematocrit for Participants Who Never Received 100 mg Open Label Sirukumab in Part B | Blood samples were collected to analyze the hematology parameter Hematocrit. Change from Baseline is presented for this parameter. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented. | Baseline (Week 0) and Weeks 4,8,12,16,24 and 36 |
| Part B: Change From Baseline in Hematology Parameter -Erythrocytes Mean Corpuscular Volume for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B | Blood samples were collected to analyze the hematology parameter Erythrocytes Mean Corpuscular Volume. Change from Baseline is presented for this parameter. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented. | Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 |
| Part B: Change From Baseline in Hematology Parameter -Erythrocytes Mean Corpuscular Volume for Participants Who Never Received 100 mg Open Label Sirukumab in Part B | Blood samples were collected to analyze the hematology parameter Hematocrit. Change from Baseline is presented for this parameter. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented. | Baseline (Week 0) and Weeks 4,8,12,16,24 and 36 |
| Part B: Change From Baseline in Hematology Parameter-Erythrocytes Mean Corpuscular Hemoglobin for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B | Blood samples were collected to analyze the hematology parameter Erythrocytes Mean Corpuscular Hemoglobin. Change from Baseline is presented for this parameter. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL Sirukumab is presented. | Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 |
| Part B: Change From Baseline in Hematology Parameter-Erythrocytes Mean Corpuscular Hemoglobin for Participants Who Never Received 100 mg Open Label Sirukumab in Part B | Blood samples were collected to analyze the hematology parameter Erythrocytes Mean Corpuscular Hemoglobin. Change from Baseline is presented for this parameter. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented. | Baseline (Week 0) and Weeks 4,8,12,16,24 and 36 |
| Part B: Change From Baseline in Hematology Parameter- Erythrocytes for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B | Blood samples were collected to analyze the hematology parameter Erythrocytes. Change from Baseline is presented for this parameter. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL Sirukumab is presented. | Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 |
| Part B: Change From Baseline in Hematology Parameter- Erythrocytes for Participants Who Never Received 100 mg Open Label Sirukumab in Part B | Blood samples were collected to analyze the hematology parameter Erythrocytes. Change from Baseline is presented for this parameter. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented. | Baseline (Week 0) and Weeks 4,8,12,16,24 and 36 |
| Part B: Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide, Chloride, Glucose, Phosphate, Potassium, Sodium and Urea for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B | Blood samples were collected to analyze the chemistry parameters including Calcium, Carbon Dioxide, Chloride, Glucose, Phosphate, Potassium, Sodium and Urea. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL Sirukumab is presented. | Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 |
| Part B: Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide, Chloride, Glucose, Phosphate, Potassium, Sodium and Urea for Participants Who Never Received 100 mg Open Label Sirukumab in Part B | Blood samples were collected to analyze the chemistry parameters including Calcium, Carbon Dioxide, Chloride, Glucose, Phosphate, Potassium, Sodium and Urea. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented. | Baseline (Week 0) and Weeks 4,8,12,16,24 and 36 |
| Part B: Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B | Blood samples were collected to analyze the chemistry parameters including Albumin and Protein. Change from Baseline is presented for these parameters. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented. | Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 |
| Part B: Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein for Participants Who Never Received 100 mg Open Label Sirukumab in Part B | Blood samples were collected to analyze the chemistry parameters including Albumin and Protein. Change from Baseline is presented for these parameters. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented. | Baseline (Week 0) and Weeks 4,8,12,16,24 and 36 |
| Part B: Change From Baseline in Clinical Chemistry Parameters: ALT, ALP and AST for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B | Blood samples were collected to analyze the chemistry parameters including ALT,ALP and AST. Change from Baseline is presented for these parameters. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented. | Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 |
| Part B: Change From Baseline in Clinical Chemistry Parameters: ALT, ALP and AST for Participants Who Never Received 100 mg Open Label Sirukumab in Part B | Blood samples were collected to analyze the chemistry parameters including ALT,ALP and AST. Change from Baseline is presented for these parameters. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented | Baseline (Week 0) and Weeks 4,8,12,16,24 and 36 |
| Part B: Change From Baseline in Clinical Chemistry Parameters: Bilirubin, Creatinine, Direct Bilirubin and Indirect Bilirubin for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B | Blood samples were collected to analyze the chemistry parameters including Albumin and Protein. Change from Baseline is presented for these parameters. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who received at least one dose of 100 mg OL sirukumab is presented. | Baseline (Week 0) and Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 |
| Part B: Change From Baseline in Clinical Chemistry Parameters: Bilirubin, Creatinine, Direct Bilirubin and Indirect Bilirubin for Participants Who Never Received 100 mg Open Label Sirukumab in Part B | Blood samples were collected to analyze the chemistry parameters including Albumin and Protein. Change from Baseline is presented for these parameters. Baseline was defined as the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Data for participants who never received 100 mg open label Sirukumab has been presented. | Baseline (Week 0) and Weeks 4,8,12,16,24 and 36 |
| Part B: Cumulative Prednisone Dose Over Time for Participants Who Received at Least One Dose of 100 mg Open-label Sirukumab in Part B | Cumulative prednisone dose is the cumulative doses taken from start of Part B. The cumulative prednisone dose at each visit was calculated based on the number of participants who attended that visit. Data for participants who received at least one dose of 100mg open label Sirukumab was presented. | Weeks 2, 4, 8, 12, 14, 16, 24, 28, 32 and 38 |
| Part B: Cumulative Prednisone Dose Over Time for Participants Who Never Received 100 mg Open Label Sirukumab in Part B | Cumulative prednisone dose is the cumulative doses taken from start of Part B. The cumulative prednisone dose at each visit was calculated based on the number of participants who attended that visit. Data for participants who never received 100 mg open label Sirukumab has been presented. | Weeks 2, 4, 8, 12, 14, 16, 24, 28, 32 and 38 |
| Part B: Number of Disease Flares Over Time | This summarizes disease flares over time with no adjustment for exposure to study drugs, calculated by taking the last visit before a participant withdrew and then counting the number of participants with at least 1 flare up to that point and summing up the total number of flares experienced by each of these participants. Data for number of disease flares per participant over time for part B were presented. | Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 |
| Part B: Number of Participants Requiring at Least One Hospitalization for Disease Flare | Number of participants with at least one flare at a given visit was the number of participants with at least one flare between first SC IP intake and the day of the given visit. The hospitalizations for disease flare were planned to be identified through the adjudication of adverse events of special interest, and include events from the category: Severe Flare including Hospitalizations. Data for participants requiring hospitalizations for disease flare for part B was not available due to early termination of study. | Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 |
| Part B: Number of Hospitalizations for Disease Flare Over Time | Number of participants with at least one flare at a given visit was the number of participants with at least one flare between first SC IP intake and the day of the given visit. The hospitalizations for disease flare were planned to be identified through the adjudication of adverse events of special interest, and include events from the category: Severe Flare including Hospitalizations. Data for participants requiring hospitalizations for disease flare for part B was not available due to early termination of study. | Up to Week 104 |
| Part B: Change From Baseline in 36-item SF-36 v2 Acute Score Over Time for Participants Who Received at Least One Dose of 100 mg OL Sirukumab in Part B | SF-36v2 acute health survey questionnaire was developed as part of the Rand Health Insurance Experiment and consists of the following 8 multi-item scales: 1. Limitations in physical functioning due to health problems, 2. Limitations in usual role activities due to physical health problems, 3. Bodily pain, 4. General mental health (psychological distress and well-being), 5. Limitations in usual role activities due to personal or emotional problems, 6. Limitations in social functioning due to physical or mental health problems. 7. Vitality (energy and fatigue) and 8. General health perception. These 8 scales were scored from 0 to 100, 0 (worst score) to 100 (best score) where higher scores indicates better health. Data for participants (Par) who received at least one dose of 100 mg OL Sirukumab has been presented. Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Day 0), Day 85, Day 87, Day 91, Day 113, Day 162, Day 339, Day 344, Week 12 and Week 24 |
| Part B: Change From Baseline in 36-item SF-36 v2 Acute Score Over Time for Participants Who Never Received 100 mg OL Sirukumab in Part B | SF-36v2 acute health survey questionnaire was developed as part of the Rand Health Insurance Experiment and consists of the following 8 multi-item scales: 1. Limitations in physical functioning due to health problems, 2. Limitations in usual role activities due to physical health problems, 3. Bodily pain, 4. General mental health (psychological distress and well-being), 5. Limitations in usual role activities due to personal or emotional problems, 6. Limitations in social functioning due to physical or mental health problems. 7. Vitality (energy and fatigue) and 8. General health perception. These 8 scales were scored from 0 to 100, 0 (worst score) to 100 (best score) where higher scores indicates better health. Data for participants (Par) who never received 100 mg OL Sirukumab has been presented. Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Day 0) and Day 23, Day 29, Day 30, Day 57, Day 59, Day 64, Day 65 , Day 85, Day 112, Day 113, Day 163, Day 169, Day 373, Week 8 and Week 12 |
| Part B: Change From Baseline in EQ-5D-5L Index Score Over Time for Participants Who Received at Least One Dose of 100 mg OL Sirukumab in Part B | EuroQoL-5 Dimensions consist of 2 elements: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D descriptive system comprised of following 5 dimensions: 1.Mobility, 2.Self-Care, 3.Usual Activities, 4.Pain/Discomfort and 5.Anxiety/Depression. Each of these 5 dimensions has 5 levels: 1: no problems; 2: slight problems; 3: moderate problems; 4: severe problems; 5: Unable to do. The digits for each of 5 dimensions were combined in a 5-digit number describing the participant's health state: e.g. state 11111 indicates no problem on any of the 5 dimensions. Index score was derived from the 5 dimensions scores using UK tariff. The weights based from the UK population was used for conversion, regardless of the origin country of participant. The score ranged from -0.594 (worst score) to 1.000 (best score). Baseline was last measurement done up to and including Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Day 0) and Day 85, Day 87, Day 91, Day 113, Day 162, Day 339, Day 344, Week 12 and Week24 |
| Part B: Change From Baseline in EQ-5D-5L Index Score Over Time for Participants Who Never Received 100mg OL Sirukumab in Part B | EuroQoL-5 Dimensions consist of 2 elements: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D descriptive system comprised of following 5 dimensions: 1.Mobility, 2.Self-Care, 3.Usual Activities, 4.Pain/Discomfort and 5.Anxiety/Depression. Each of these 5 dimensions has 5 levels: 1: no problems; 2: slight problems; 3: moderate problems; 4: severe problems; 5: Unable to do. The digits for each of 5 dimensions were combined in a 5-digit number describing the participant's health state: e.g. state 11111 indicates no problem on any of the 5 dimensions. Index score was derived from the 5 dimensions scores using UK tariff. The weights based from the UK population was used for conversion, regardless of the origin country of participant. The score ranged from -0.594 (worst score) to 1.000 (best score). Baseline was last measurement done up to and including Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Day 0) and Day 29, 30, 57, 59, 64, 65, 85, 112, 113,163,169 and 373, Week 12 |
| Part B: Change From Baseline in FACIT-Fatigue Scores Over Time for Participants Who Received at Least One Dose of 100 mg OL Sirukumab in Part B | The FACIT-Fatigue is a 13-item questionnaire formatted for self-administration that assesses participant reported fatigue and its impact upon daily activities and function over the past seven days. Participants were asked to answer each question using a 5-point Likert-type scale (4 = Not at all; 3 = A little bit; 2 = Somewhat; 3 = Quite a bit; and 0 = Very Much) where 0 is a bad response and 4 is good response. Each of the 13 items of the FACIT-Fatigue Scale ranges from 0-4, with a range of possible total score from 0-52, 0 (Extreme fatigue) to 52 (No fatigue) where 0 being the worst possible score and 52 the best (i.e. less fatigue). Scores below 30 indicate severe fatigue. Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Day 0) and Day 85,87,91,113,162, 344,339,Week 12, 24 |
| Part B: Change From Baseline in FACIT-Fatigue Scores Over Time for Participants Who Never Received 100mg OL Sirukumab in Part B | The FACIT-Fatigue is a 13-item questionnaire formatted for self-administration that assesses participant reported fatigue and its impact upon daily activities and function over the past seven days. Participants were asked to answer each question using a 5-point Likert-type scale (4 = Not at all; 3 = A little bit; 2 = Somewhat; 3 = Quite a bit; and 0 = Very Much) where 0 is a bad response and 4 is good response. Each of the 13 items of the FACIT-Fatigue Scale ranges from 0-4, with a range of possible total score from 0-52, 0 (Extreme fatigue) to 52 (No fatigue) where 0 being the worst possible score and 52 the best (i.e. less fatigue). Scores below 30 indicate severe fatigue. Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Participants with post baseline data were reported. | Baseline (Day 0) and Day 85,87,91,113,162 344,339,Week 12, 24 |
| Part B: Change From Baseline in Pain NRS Scores Over Time for Participants Who Received at Least One Dose of 100 mg OL Sirukumab in Part B | The assessment of pain severity was made using a single pain severity item on which participants were asked to rate the severity of their average pain now on an 11-point numeric rating scale ranging from 0, no pain to 10, the worst pain imaginable. Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Day 0) and Day 85,87,91,113,162 344,339,Week 12, 24 |
| Part B: Change From Baseline in Pain NRS Scores Over Time for Participants Who Never Received at Least One Dose of 100mg OL Sirukumab in Part B | The assessment of pain severity was made using a single pain severity item on which participants were asked to rate the severity of their average pain now on an 11-point numeric rating scale ranging from 0, no pain to 10, the worst pain imaginable. Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Participants with post baseline data were reported. | Baseline (Day 0) and Day 85,87,91,113,162 344,339,Week 12, 24 |
| Part B: HAQDI Score Over Time for Participants Who Received at Least One Dose of 100 mg OL Sirukumab in Part B | Health Assessment Questionnaire-Disability Index (HAQ-DI) indicates the extent of participant's functional ability during the past week, and was assessed for subgroup of participants with symptoms of Polymyalgia Rheumatic (PMR). HAQ-DI included 20 questions in 8 categories of functioning - dressing and grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Each functional area contains at least two questions. For each question, there is a 4-level difficulty scale that is scored from 0 (minimum) to 3 (Maximum), representing no difficulty (0), some difficulty (1), much difficulty (2), and unable to do (3) where, lower score indicates less disability and higher scores indicates worse disability. Total score was calculated as average scores of 20 questions which can be interpreted in terms of 3 categories: from 0 to 1: mild difficulties to moderate disability, from 1 to 2: disability moderate to severe, from 2 to 3: severe to very severe disability | Day 87, 339, 344, Week 12, 24 |
| Part B: HAQDI Score Over Time for Participants Who Never Received 100 mg OL Sirukumab in Part B | Health Assessment Questionnaire-Disability Index (HAQ-DI) indicates the extent of participant's functional ability during the past week, and was assessed for subgroup of participants with symptoms of Polymyalgia Rheumatic (PMR). HAQ-DI included 20 questions in 8 categories of functioning - dressing and grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Each functional area contains at least two questions. For each question, there is a 4-level difficulty scale that is scored from 0 (minimum) to 3 (Maximum), representing no difficulty (0), some difficulty (1), much difficulty (2), and unable to do (3) where, lower score indicates less disability and higher scores indicates worse disability. Total score was calculated as average scores of 20 questions which can be interpreted in terms of 3 categories: from 0 to 1: mild difficulties to moderate disability, from 1 to 2: disability moderate to severe, from 2 to 3: severe to very severe disability | Day 29, 64, 65, 85, 112, 113, 169, 373 and Week 12 |
| Part B: Change From Baseline in PtGA Score for Participants Who Received at Least One Dose of 100 mg OL Sirukumab in Part B | The Patient's Global Assessments of Disease Activity was recorded on a Visual analog scale (VAS). of 10 centimeter (cm) ranging from 0 (very well) to 10 (very poor). Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Day 0), Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38, 40; Days 85, 87, 91, , 113, 162, 339, and 344 |
| Part B: Change From Baseline in PtGA Score for Participants Who Never Received 100 mg OL Sirukumab in Part B | The Patient's Global Assessments of Disease Activity was recorded on a Visual analog scale (VAS). of 10 centimeter (cm) ranging from 0 (very well) to 10 (very poor). Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Participants with post baseline data were reported. | Baseline (Day 0), Weeks 2, 4, 8, 12, 16, 36; Days 23, 29, 30, 57, 59, 64, 65, 85,112, 113, 115, 163, 169 and 373 |
| Part B: Change From Baseline in PhGA Score for Participants Who Received at Least One Dose of 100 mg OL Sirukumab in Part B | In PhGA was based on What is physician's assessment of the participant's current disease activity. PhGA used a 10 cm VAS ranging from 0 (none) to 10 (extremely active). Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Day 0) and Day 85, Day 113, Day 162, Day 203, Day 339, Day 344, Week 2, Week 4, Week 8, Week 12, Week 14, Week 16, Week 24, Week 36, Week 38, Week 40 |
| Part B: Change From Baseline in PhGA Score for Participants Who Never Received 100 mg OL Sirukumab in Part B | In PhGA was based on What is physician's assessment of the participant's current disease activity. PhGA used a 10 cm VAS ranging from 0 (none) to 10 (extremely active). Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. Participants with post baseline data were reported. | Baseline (Day 0), Weeks 4, 8, 12, 16, 36; Days 23, 29, 30, 57, 59, 64, 65, 85, 112, 113, 163, 169 and 373 |
| Part B: Number of Participants With PGIC Score Over Time Who Received at Least One Dose of 100 mg OL Sirukumab in Part B | Patient-reported response to treatment was assessed using the PGIC measure, a single item completed by participant to provide a clinically meaningful summary of an individual's response to treatment. The assessment provides an estimate of the magnitude of treatment response at different time points during the study. Responses include: Much Better, Better, Slightly Better, No Change, Slightly Worse, Worse, and Much Worse. The categorical data of participant rating of change is summarized by treatment group, visit and response category. | Baseline (Day 1), Days 103 and 271 |
| Part B: Number of Participants With PGIC Score Over Time Who Never Received 100 mg OL Sirukumab in Part B | Patient-reported response to treatment was assessed using the PGIC measure, a single item completed by participant to provide a clinically meaningful summary of an individual's response to treatment. The assessment provides an estimate of the magnitude of treatment response at different time points during the study. Responses include: Much Better, Better, Slightly Better, No Change, Slightly Worse, Worse, and Much Worse. The categorical data of participant rating of change is summarized by treatment group, visit and response category. | Baseline (Day 1) |
| Part B: Change From Baseline in CRP Over Time for Participants Who Received at Least One Dose of 100 mg OL Sirukumab in Part B | Blood samples were collected for analysis of CRP. Data for Change from Baseline in serum CRP over time for part B was reported. Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Day 0), Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 |
| Part B: Change From Baseline in CRP Over Time for Participants Who Never Received 100 mg OL Sirukumab in Part B | Blood samples were collected for analysis of CRP. Data for Change from Baseline in serum CRP over time for part B was reported. Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Day 0), Weeks 4, 8, 12, 16, 24 and 36 |
| Part B: Change From Baseline in ESR Over Time for Participants Who Received at Least One Dose of 100 mg OL Sirukumab in Part B | Blood samples were collected for analysis of ESR. Data for Change from Baseline in ESR over time for part A was reported. Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Day 0), Weeks 2, 4, 8, 12, 14, 16, 24, 36, 38 and 40 |
| Part B: Change From Baseline in ESR Over Time for Participants Who Never Received 100 mg OL Sirukumab in Part B | Blood samples were collected for analysis of ESR. Data for Change from Baseline in ESR over time for part A was reported. Baseline was the last measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Day 0), Weeks 4, 8, 12, 16, 24 and 36 |
| Part B: Change From Baseline in EQ-5D-5L VAS Over Time for Participants Who Received at Least One Dose of 100 mg OL Sirukumab in Part B | EQ-5D essentially consists of 2 elements: the EQ-5D descriptive system and the EQ VAS. The EQ-5D descriptive system comprised of the following 6 dimensions: 1.Mobility, 2.Self, 3.Usual Activities, 4.Pain/Discomfort, 5.Anxiety/Depression; 6.How good or or bad your health is today. Each of these 6 dimensions has 5 levels: 1: no problems; 2: slight problems; 3: moderate problems; 4: severe problems; 5: Unable to do. The EQ VAS records the respondent's self-rated health on a vertical line, VAS where the endpoints are 'Best imaginable health state' and 'Worst imaginable health state'. Answers to 'How good or bad your health is today' were measured on a 100 point VAS scale. Baseline for Part B is the last non-missing measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Day 0) and Days 85, 87, 91, 113, 162, 339 and 344 and Weeks 12 and 24 |
| Part B: Change From Baseline in EQ-5D-5L VAS Over Time for Participants Who Never Received 100 mg OL Sirukumab in Part B | EQ-5D essentially consists of 2 elements: the EQ-5D descriptive system and the EQ VAS. The EQ-5D descriptive system comprised of the following 6 dimensions: 1.Mobility, 2.Self, 3.Usual Activities, 4.Pain/Discomfort, 5.Anxiety/Depression; 6.How good or or bad your health is today. Each of these 6 dimensions has 5 levels: 1: no problems; 2: slight problems; 3: moderate problems; 4: severe problems; 5: Unable to do. The EQ VAS records the respondent's self-rated health on a vertical line, VAS where the endpoints are 100 (Best imaginable health state) and 0 (Worst imaginable health state). Answers to 'How good or bad your health is today' were measured on a 100 point VAS scale. Baseline for Part B is the last non-missing measurement done up to and including the Week 52 visit date of Part A. Change from Baseline was defined as post-Baseline value minus Baseline value. | Baseline (Day 0) and Days 23, 29, 30, 57, 59, 64, 65, 85, 112, 113, 163, 169, 344 and 373 and Week 12 |
Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Giant Cell Arteritis, Sirukumab, Prednisone
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NCT04365491
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European Society for Trauma and Emergency Surgery (ESTES) Cohort Study Snapshot Audit 2020 - Acute Appendicitis
|
Background Acute appendicitis is an extremely common surgical emergency. Traditionally, appendicitis has been managed surgically. Recently, however, variability in management of acute appendicitis has emerged, with some clinicians practising conservative, i.e. non-operative, management in selected patients. This high-quality pan-European, prospective audit will establish current practices and correlate them against outcomes.~Aim To explore differences in patient presentation, clinical course and outcomes for acute appendicitis across international clinical Centres to identify areas of practice variability in the presentation, management and complications of acute appendicitis.~Endpoints A three-stage data collection strategy will be used in this audit. There will be a 90 day prospective period for data collection during a six month window from September 2020 to end February 2021. Data collection will consist of collecting patient demographics, details of management (conservative vs surgical) and outcomes. Several outcomes measures will be used, including surgical mortality, morbidity (Clavien-Dindo Grade 2 and above) and length of hospital stay.~The data collection points are as follows:~90 Day Prospective Audit Collecting anytime during 6-month window:~Demographics~Operative technique~Use of antibiotics~Conservative vs surgical management~Outcomes~All eligible patients will be followed up to 90 days from their admission~Readmissions will be flagged and identified~Complications within the 90 day period will be recorded~Patients who have a complete data set at 90 days post presentation will be followed up to the 1-year mark • Incomplete data sets will be excluded from the study~Methods: This 90 day prospective audit will be performed across Europe from September 2020 to end February 2021., and will be co-ordinated by a designated committee of European Society of Trauma and Emergency Surgery. This will be preceded by a one-week, three-Centre pilot. Sites will be asked to pre-register for the audit and will be required to obtain appropriate regional or national approvals in advance of the enrolment date.~During the study period, all eligible patients with acute appendicitis will be recorded contemporaneously and followed-up through to 90 days from their admission. The audit will be performed using a standardised pre-determined protocol, instrument and a secure online database. The report of this audit will be prepared in accordance with guidelines set by the STROBE (strengthening the reporting of observational studies in epidemiology) statement for observational studies.~Discussion: This multi-centre, snapshot audit will be delivered by emergency surgeons and trainees in an coordinated and homogenous manner. The data obtained about areas of variability in provision or practice, and how this may impact upon outcomes, will serve to improve overall patient care as well as being hypothesis generating and inform areas needing future prospective study.
|
European Society for Trauma and Emergency Surgery (ESTES) Cohort Study Snapshot Audit 2020 - Acute Appendicitis
|
Appendicitis
|
6.4 Inclusion Criteria~Adult patients (≥16 years of age) admitted for:~Acute Appendicitis~Procedures which should be included:~Appendectomy (open, laparoscopic or robotic)~Diagnostic laparoscopy~Partial right hemicolectomy (for appendiceal mass or carcinoid tumour) Exclusion Criteria~Mesenteric adenitis~Ovarian pathology~Methods for identifying patients~Multiple methods may be used according to local circumstances/staffing:~Daily review of emergency department (non-operative) and operating room lists~Daily review of team handover sheets / emergency admission lists / ward lists~Review of operating room logbooks~Use of electronic systems to flag any readmissions of patients identified and treated
|
16 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of acute appendicitis | Incidence of acute appendicitis | 3 months |
|
Appendicitis, Emergencies, Disease Attributes, Pathologic Processes, Intraabdominal Infections, Infections, Gastroenteritis, Gastrointestinal Diseases, Digestive System Diseases, Cecal Diseases, Intestinal Diseases
|
European Society for Trauma and Emergency Surgery (ESTES) Cohort Study Snapshot Audit 2020 - Acute Appendicitis
Study Overview
=================
Brief Summary
-----------------
Background Acute appendicitis is an extremely common surgical emergency. Traditionally, appendicitis has been managed surgically. Recently, however, variability in management of acute appendicitis has emerged, with some clinicians practising conservative, i.e. non-operative, management in selected patients. This high-quality pan-European, prospective audit will establish current practices and correlate them against outcomes. Aim To explore differences in patient presentation, clinical course and outcomes for acute appendicitis across international clinical Centres to identify areas of practice variability in the presentation, management and complications of acute appendicitis. Endpoints A three-stage data collection strategy will be used in this audit. There will be a 90 day prospective period for data collection during a six month window from September 2020 to end February 2021. Data collection will consist of collecting patient demographics, details of management (conservative vs surgical) and outcomes. Several outcomes measures will be used, including surgical mortality, morbidity (Clavien-Dindo Grade 2 and above) and length of hospital stay. The data collection points are as follows: 90 Day Prospective Audit Collecting anytime during 6-month window: Demographics Operative technique Use of antibiotics Conservative vs surgical management Outcomes All eligible patients will be followed up to 90 days from their admission Readmissions will be flagged and identified Complications within the 90 day period will be recorded Patients who have a complete data set at 90 days post presentation will be followed up to the 1-year mark • Incomplete data sets will be excluded from the study Methods: This 90 day prospective audit will be performed across Europe from September 2020 to end February 2021., and will be co-ordinated by a designated committee of European Society of Trauma and Emergency Surgery. This will be preceded by a one-week, three-Centre pilot. Sites will be asked to pre-register for the audit and will be required to obtain appropriate regional or national approvals in advance of the enrolment date. During the study period, all eligible patients with acute appendicitis will be recorded contemporaneously and followed-up through to 90 days from their admission. The audit will be performed using a standardised pre-determined protocol, instrument and a secure online database. The report of this audit will be prepared in accordance with guidelines set by the STROBE (strengthening the reporting of observational studies in epidemiology) statement for observational studies. Discussion: This multi-centre, snapshot audit will be delivered by emergency surgeons and trainees in an coordinated and homogenous manner. The data obtained about areas of variability in provision or practice, and how this may impact upon outcomes, will serve to improve overall patient care as well as being hypothesis generating and inform areas needing future prospective study.
Official Title
-----------------
European Society for Trauma and Emergency Surgery (ESTES) Cohort Study Snapshot Audit 2020 - Acute Appendicitis
Conditions
-----------------
Appendicitis
Participation Criteria
=================
Eligibility Criteria
-----------------
6.4 Inclusion Criteria Adult patients (≥16 years of age) admitted for: Acute Appendicitis Procedures which should be included: Appendectomy (open, laparoscopic or robotic) Diagnostic laparoscopy Partial right hemicolectomy (for appendiceal mass or carcinoid tumour) Exclusion Criteria Mesenteric adenitis Ovarian pathology Methods for identifying patients Multiple methods may be used according to local circumstances/staffing: Daily review of emergency department (non-operative) and operating room lists Daily review of team handover sheets / emergency admission lists / ward lists Review of operating room logbooks Use of electronic systems to flag any readmissions of patients identified and treated
Ages Eligible for Study
-----------------
Minimum Age: 16 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of acute appendicitis | Incidence of acute appendicitis | 3 months |
|
||||||
NCT04805892
|
Study Utilizing BIOZEK COVID-19 Antigen Rapid Test.
|
This is a research study to evaluate the Sensitivity and Specificity of BIOZEK COVID-19 Antigen Rapid Test on samples collected by a healthcare professional versus self-collection; and to perform analysis to compare results. In addition, to obtain RT-PCR test results, performed prior to enrollment, and compare all three results.
|
Open Label, Single-Center Study Utilizing BIOZEK COVID-19 Antigen Rapid Test as Compared to Standard Testing Technique. Test Performed by a Professional Versus Self-collection and Standard of Care
|
Covid19
|
* Diagnostic Test: BIOZEK COVID-19 Antigen Rapid Test
|
Inclusion Criteria:~Subjects must be ≥18 years of age and have had an RT-PCR test performed prior to enrollment.~Subjects must be able to understand and willingly sign a written informed consent. Additionally, participants need to meet at least 1 of the criteria listed below:~Currently experiencing symptoms of COVID-19.~Be clinically diagnosed or suspected to have COVID-19.~Recent past (3 weeks) exhibited symptoms of COVID-19.~Be capable of performing a self-collection of a nasopharyngeal sample with use of nasal swab kit.~Interacted with a COVID-19 positive individual.~Exclusion Criteria:~Subjects who meet any of the following exclusion criteria may not be enrolled in this study:~Cannot perform self-collection of a nasopharyngeal sample with use of nasal swab kit.~Have a deviated nasal septum.~Cognitively impaired individuals resulting in the inability to provide informed consent
|
18 Years
| null |
All
|
No
|
Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity and Specificity of BIOZEK COVID-19 Antigen Rapid Test on a Sample Collected by Healthcare Professionals. | The Biozek Antigen Rapid Tests performed by the trained study personnel on the samples collected by the trained study personnel. Sensitivity was calculated using (TP/TP+FN)*100% formula.~Specificity was calculated using (TN/TN+FP)*100% formula. | 1 visit, up to 2 hours |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity and Specificity of BIOZEK COVID-19 Antigen Rapid Test on Self - Collected Samples. | The Biozek Antigen Rapid Tests self-performed performed by the subject on the self - collected samples by the subjects. Sensitivity was calculated using (TP/TP+FN)*100% formula.~Specificity was calculated using (TN/TN+FP)*100% formula. | 1 visit, up to 2 hours |
|
COVID-19, Pneumonia, Viral, Pneumonia, Respiratory Tract Infections, Infections, Virus Diseases, Coronavirus Infections, Coronaviridae Infections, Nidovirales Infections, RNA Virus Infections, Lung Diseases, Respiratory Tract Diseases
|
| Intervention/Treatment |
| --- |
|Diagnostic Test: BIOZEK COVID-19 Antigen Rapid Test|The BIOZEK COVID-19 Antigen Rapid Test is used for the detection of SARS-CoV-2 antigens in nasopharyngeal swab specimens from individuals who are suspected of having COVID-19.|
|
Study Utilizing BIOZEK COVID-19 Antigen Rapid Test.
Study Overview
=================
Brief Summary
-----------------
This is a research study to evaluate the Sensitivity and Specificity of BIOZEK COVID-19 Antigen Rapid Test on samples collected by a healthcare professional versus self-collection; and to perform analysis to compare results. In addition, to obtain RT-PCR test results, performed prior to enrollment, and compare all three results.
Official Title
-----------------
Open Label, Single-Center Study Utilizing BIOZEK COVID-19 Antigen Rapid Test as Compared to Standard Testing Technique. Test Performed by a Professional Versus Self-collection and Standard of Care
Conditions
-----------------
Covid19
Intervention / Treatment
-----------------
* Diagnostic Test: BIOZEK COVID-19 Antigen Rapid Test
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects must be ≥18 years of age and have had an RT-PCR test performed prior to enrollment. Subjects must be able to understand and willingly sign a written informed consent. Additionally, participants need to meet at least 1 of the criteria listed below: Currently experiencing symptoms of COVID-19. Be clinically diagnosed or suspected to have COVID-19. Recent past (3 weeks) exhibited symptoms of COVID-19. Be capable of performing a self-collection of a nasopharyngeal sample with use of nasal swab kit. Interacted with a COVID-19 positive individual. Exclusion Criteria: Subjects who meet any of the following exclusion criteria may not be enrolled in this study: Cannot perform self-collection of a nasopharyngeal sample with use of nasal swab kit. Have a deviated nasal septum. Cognitively impaired individuals resulting in the inability to provide informed consent
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Intervention/Treatment |
| --- |
|Diagnostic Test: BIOZEK COVID-19 Antigen Rapid Test|The BIOZEK COVID-19 Antigen Rapid Test is used for the detection of SARS-CoV-2 antigens in nasopharyngeal swab specimens from individuals who are suspected of having COVID-19.|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity and Specificity of BIOZEK COVID-19 Antigen Rapid Test on a Sample Collected by Healthcare Professionals. | The Biozek Antigen Rapid Tests performed by the trained study personnel on the samples collected by the trained study personnel. Sensitivity was calculated using (TP/TP+FN)*100% formula. Specificity was calculated using (TN/TN+FP)*100% formula. | 1 visit, up to 2 hours |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity and Specificity of BIOZEK COVID-19 Antigen Rapid Test on Self - Collected Samples. | The Biozek Antigen Rapid Tests self-performed performed by the subject on the self - collected samples by the subjects. Sensitivity was calculated using (TP/TP+FN)*100% formula. Specificity was calculated using (TN/TN+FP)*100% formula. | 1 visit, up to 2 hours |
|
||
NCT05359367
|
A Novel Approach to Enhance True Recovery After Stroke
|
The purpose of this study is to elucidate pathophysiological mechanisms behind gait disturbances during the early recovery phase after hemiparetic stroke to identify targets for new treatment strategies.~Using an explorative, observational study design, pathophysiological mechanisms at play during the early recovery phase will be monitored, by repeated clinical assessments during inpatient rehabilitation as well as examinations of muscle activation patterns, kinematics of walking, corticospinal and reticulospinal function < 1 month, 3 and 6 months after hemiparetic stroke.~Inclusion: Eligible patients will have suffered a stroke, verified by CT or MRI examination and are admitted to inpatient care at the University Department of Rehabilitation Medicine Danderyd Hospital (RUDS). Thirty patients will be included consecutively. With an anticipated loss of 4-10 patients, at least 20 are expected to complete the study.~The clinical assessment protocols include standardized measures for the assessment of clinical and self-perceived aspects of functioning and disability. These assessments will be performed and repeated < 1 month, at 3 months and 6 months post-stroke by a therapist not responsible for rehabilitation interventions. At each of these assessment instances, laboratory movement analysis including electromyography (EMG) and ultrasound of the lower extremity muscle will be performed. In addition, a short assessment of body function and activity will be performed weekly during inpatient rehabilitation.
|
A Novel Approach to the Development of New Treatment Strategies to Enhance True Recovery After Stroke, Based on Laboratory Movement Analysis and Clinical Aspects of Gait Function and Walking
|
Stroke, Inpatients, Recovery of Function, Observational Study
|
* Diagnostic Test: Observational
|
Inclusion Criteria:~Participants with hemiplegia, dependence in ambulation (1- 4 according to the Functional Ambulation Categories (FAC)),~>= 50 points on the Trunk Control Test.~Impaired dorsiflexion manifested as impaired voluntarily dorsiflexion and inability to hold the ankle in a dorsiflexed position while sitting, and for ambulatory participants, impaired dorsiflexion during swing phase and initial contact during visual inspection of gait.~Recommended for an ancle foot orthosis (AFO) by an experienced physiotherapist. Able to understand study information and provide informed consent.~Exclusion Criteria:~Contracture that severely restricts gait movements in a lower limb joint,~cardiovascular or other somatic condition incompatible with intensive gait training,~notifiable infectious disease, contagious infections (e.g. MRSA or ESBL)~Inability to participate in the rehabilitation intervention due to behavioral or psychiatric disorder~when magnetic resonance imaging will be performed, additional exclusion criteria are current or history of epilepsy, metal implants in the brain/skull cochlear implants, any implanted neurostimulator, cardiac pacemaker or cardiac implants of metal and infusion device.
|
18 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fugl-Meyer score (FMA-LE) | Assesses sensory and movement related functions in the lower extremity (0p max impairment summed up to 86p max no detected impairment) | At baseline, weekly during inpatient rehab and at 3 and 6 months to assess change. |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Motion analysis during gait | In a movement laboratory (Vicon V16), data for motion analysis will be collected by assessing orientation of body segments and joint angle trajectories and forces by means of force plates (AMTI) during walking. | At baseline, at 3 and 6 months to assess change. |
| Electromyography (EMG) | EMG is used to measure muscle activation patterns during gait. | At baseline, at 3 and 6 months to assess change. |
| Neuroflexor | Medical technology device. Assesses spasticity by identifying the neural, viscous and elastic components during passive movement using a biomechanical algorithm (presented in Newton) | At baseline, at 3 and 6 months to assess change. |
| Modified Ashworth scale 0-5 | Assesses spasticity on a 6 point scale/muscle (0p no impairment, 5p max impairment/muscle) | At baseline, weekly during inpatient rehab and at 3 and 6 months to assess change. |
| Passive range of motion in the lower extremity | Clinical assessment of range of motion with a goniometer | At baseline, weekly during inpatient rehab and at 3 and 6 months to assess change. |
| The 10 meter walk test | Assesses gait speed | At baseline, weekly during inpatient rehab and at 3 and 6 months to assess change. |
| 6 minutes walk test | Assesses walking endurance in meters walked | At baseline, weekly during inpatient rehab and at 3 and 6 months to assess change. |
| Rated Perceived Exertion (RPE) Scale | Ratings (min 6, max 20) according to the RPE scale are made at the end of the 6 minutes walk test. | At baseline, weekly during inpatient rehab and at 3 and 6 months to assess change. |
| The Functional Ambulation Categories (FAC) | Assesses independence in walking (0p nonfunctional, 5p independent) Total score 0-5p | At baseline, weekly during inpatient rehab and at 3 and 6 months to assess change. |
| The Balance evaluation systems test (BEST-test) | Assesses postural control, incorporating bio-mechanical systems, limits of stability, anticipatory postural adjustment, automatic postural responses, sensory orientation, stability in gait (0p max impairment summed up to 108p no impairment) | At baseline, weekly during inpatient rehab and at 3 and 6 months to assess change. |
| Falls Efficacy Scale (FES-S) | Assesses self perceived balance in every day life activities rated on a 11 point scale (0p not safe at all 10p completely safe). Total score: 0- 130 p | At baseline and at 3 and 6 months to assess change. |
| Navigated Transcranial magnetic stimulation (nTMS) | To estimate the integrity of the corticospinal tract, transcraniel magnetic stimulation will be applied to the primary motor cortex and motor evoked potentials will be will be recorded from the lower leg muscles using electromyography. | At baseline and at 3 and 6 months to assess change. |
| The Montreal Cognitive Assessment (MoCa) | Assesses mental function (0p max impairment summed up to 30p no detected impairment) | At baseline and at 3 and 6 months to assess change. |
| National Institute of Health Stroke Scale | To assess overall effects of stroke (ranging from 0-44 points, a higher score indicating more severe disability). | At baseline and at 3 and 6 months to assess change. |
| Barthel Index | Assesses independence in mobility and personal care (0p dependent 10/15p independent) Total score 0-100p | At baseline, weekly during inpatient rehab and at 3 and 6 months to assess change. |
| Monofilament | Measuring cutaneous sensory perception threshold under foot with a pressure of 4, 6 and 10 grams. | At baseline, at 3 and 6 months to assess change. |
| Pain drawing | Self-assessed location and type of pain on the body | At baseline, weekly during inpatient rehab and at 3 and 6 months to assess change. |
| Numeric rating scale of pain | Self-rated general intensity of pain at time of assessment (0 no pain, 10 worst imaginable pain) | At baseline, weekly during inpatient rehab and at 3 and 6 months to assess change. |
| Medical Research Council scale | Assesses movement strength at a specific joint and motion (0 no muscle activity 5 normal force) | At baseline, weekly during inpatient rehab and at 3 and 6 months to assess change. |
| Walking impact scale (Walk-12) | Measures rated limitations in walking activities (1 no limitation, 5 extreme limitation) | At baseline and at 3 and 6 months to assess change |
|
Stroke, Cerebrovascular Disorders, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Vascular Diseases, Cardiovascular Diseases
|
| Intervention/Treatment |
| --- |
|Diagnostic Test: Observational|Laboratory movement analysis, navigated transcranial magnetic stimulation and clinical aspects of gait function and walking.|
|
A Novel Approach to Enhance True Recovery After Stroke
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to elucidate pathophysiological mechanisms behind gait disturbances during the early recovery phase after hemiparetic stroke to identify targets for new treatment strategies. Using an explorative, observational study design, pathophysiological mechanisms at play during the early recovery phase will be monitored, by repeated clinical assessments during inpatient rehabilitation as well as examinations of muscle activation patterns, kinematics of walking, corticospinal and reticulospinal function < 1 month, 3 and 6 months after hemiparetic stroke. Inclusion: Eligible patients will have suffered a stroke, verified by CT or MRI examination and are admitted to inpatient care at the University Department of Rehabilitation Medicine Danderyd Hospital (RUDS). Thirty patients will be included consecutively. With an anticipated loss of 4-10 patients, at least 20 are expected to complete the study. The clinical assessment protocols include standardized measures for the assessment of clinical and self-perceived aspects of functioning and disability. These assessments will be performed and repeated < 1 month, at 3 months and 6 months post-stroke by a therapist not responsible for rehabilitation interventions. At each of these assessment instances, laboratory movement analysis including electromyography (EMG) and ultrasound of the lower extremity muscle will be performed. In addition, a short assessment of body function and activity will be performed weekly during inpatient rehabilitation.
Official Title
-----------------
A Novel Approach to the Development of New Treatment Strategies to Enhance True Recovery After Stroke, Based on Laboratory Movement Analysis and Clinical Aspects of Gait Function and Walking
Conditions
-----------------
Stroke, Inpatients, Recovery of Function, Observational Study
Intervention / Treatment
-----------------
* Diagnostic Test: Observational
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants with hemiplegia, dependence in ambulation (1- 4 according to the Functional Ambulation Categories (FAC)), >= 50 points on the Trunk Control Test. Impaired dorsiflexion manifested as impaired voluntarily dorsiflexion and inability to hold the ankle in a dorsiflexed position while sitting, and for ambulatory participants, impaired dorsiflexion during swing phase and initial contact during visual inspection of gait. Recommended for an ancle foot orthosis (AFO) by an experienced physiotherapist. Able to understand study information and provide informed consent. Exclusion Criteria: Contracture that severely restricts gait movements in a lower limb joint, cardiovascular or other somatic condition incompatible with intensive gait training, notifiable infectious disease, contagious infections (e.g. MRSA or ESBL) Inability to participate in the rehabilitation intervention due to behavioral or psychiatric disorder when magnetic resonance imaging will be performed, additional exclusion criteria are current or history of epilepsy, metal implants in the brain/skull cochlear implants, any implanted neurostimulator, cardiac pacemaker or cardiac implants of metal and infusion device.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Intervention/Treatment |
| --- |
|Diagnostic Test: Observational|Laboratory movement analysis, navigated transcranial magnetic stimulation and clinical aspects of gait function and walking.|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fugl-Meyer score (FMA-LE) | Assesses sensory and movement related functions in the lower extremity (0p max impairment summed up to 86p max no detected impairment) | At baseline, weekly during inpatient rehab and at 3 and 6 months to assess change. |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Motion analysis during gait | In a movement laboratory (Vicon V16), data for motion analysis will be collected by assessing orientation of body segments and joint angle trajectories and forces by means of force plates (AMTI) during walking. | At baseline, at 3 and 6 months to assess change. |
| Electromyography (EMG) | EMG is used to measure muscle activation patterns during gait. | At baseline, at 3 and 6 months to assess change. |
| Neuroflexor | Medical technology device. Assesses spasticity by identifying the neural, viscous and elastic components during passive movement using a biomechanical algorithm (presented in Newton) | At baseline, at 3 and 6 months to assess change. |
| Modified Ashworth scale 0-5 | Assesses spasticity on a 6 point scale/muscle (0p no impairment, 5p max impairment/muscle) | At baseline, weekly during inpatient rehab and at 3 and 6 months to assess change. |
| Passive range of motion in the lower extremity | Clinical assessment of range of motion with a goniometer | At baseline, weekly during inpatient rehab and at 3 and 6 months to assess change. |
| The 10 meter walk test | Assesses gait speed | At baseline, weekly during inpatient rehab and at 3 and 6 months to assess change. |
| 6 minutes walk test | Assesses walking endurance in meters walked | At baseline, weekly during inpatient rehab and at 3 and 6 months to assess change. |
| Rated Perceived Exertion (RPE) Scale | Ratings (min 6, max 20) according to the RPE scale are made at the end of the 6 minutes walk test. | At baseline, weekly during inpatient rehab and at 3 and 6 months to assess change. |
| The Functional Ambulation Categories (FAC) | Assesses independence in walking (0p nonfunctional, 5p independent) Total score 0-5p | At baseline, weekly during inpatient rehab and at 3 and 6 months to assess change. |
| The Balance evaluation systems test (BEST-test) | Assesses postural control, incorporating bio-mechanical systems, limits of stability, anticipatory postural adjustment, automatic postural responses, sensory orientation, stability in gait (0p max impairment summed up to 108p no impairment) | At baseline, weekly during inpatient rehab and at 3 and 6 months to assess change. |
| Falls Efficacy Scale (FES-S) | Assesses self perceived balance in every day life activities rated on a 11 point scale (0p not safe at all 10p completely safe). Total score: 0- 130 p | At baseline and at 3 and 6 months to assess change. |
| Navigated Transcranial magnetic stimulation (nTMS) | To estimate the integrity of the corticospinal tract, transcraniel magnetic stimulation will be applied to the primary motor cortex and motor evoked potentials will be will be recorded from the lower leg muscles using electromyography. | At baseline and at 3 and 6 months to assess change. |
| The Montreal Cognitive Assessment (MoCa) | Assesses mental function (0p max impairment summed up to 30p no detected impairment) | At baseline and at 3 and 6 months to assess change. |
| National Institute of Health Stroke Scale | To assess overall effects of stroke (ranging from 0-44 points, a higher score indicating more severe disability). | At baseline and at 3 and 6 months to assess change. |
| Barthel Index | Assesses independence in mobility and personal care (0p dependent 10/15p independent) Total score 0-100p | At baseline, weekly during inpatient rehab and at 3 and 6 months to assess change. |
| Monofilament | Measuring cutaneous sensory perception threshold under foot with a pressure of 4, 6 and 10 grams. | At baseline, at 3 and 6 months to assess change. |
| Pain drawing | Self-assessed location and type of pain on the body | At baseline, weekly during inpatient rehab and at 3 and 6 months to assess change. |
| Numeric rating scale of pain | Self-rated general intensity of pain at time of assessment (0 no pain, 10 worst imaginable pain) | At baseline, weekly during inpatient rehab and at 3 and 6 months to assess change. |
| Medical Research Council scale | Assesses movement strength at a specific joint and motion (0 no muscle activity 5 normal force) | At baseline, weekly during inpatient rehab and at 3 and 6 months to assess change. |
| Walking impact scale (Walk-12) | Measures rated limitations in walking activities (1 no limitation, 5 extreme limitation) | At baseline and at 3 and 6 months to assess change |
|
|||
NCT03944252
|
Cetuximab + Avelumab or Avelumab Alone for Unresectable, Locally Advanced or Metastatic Squamous Cell Anal Carcinoma (SCCAC) Progressed After at Least One Line of Systemic Treatment (CARACAS)
|
The standard first line treatment in SCCAC is the association of 5-FU with cisplatin reaching a percentage of survival at 5 years of about 32% (Faivre 1999); in a recent case series of patients affected by SCCAC, the combination of 5-FU and cisplatin as first line treatment produced 34.4% objective response rate (ORR) and a 5 years survival rate of 15% (Sclafani 2017);~No standard second line treatment exists for SCCAC;~Cetuximab in association with irinotecan has demonstrated promising results in pretreated patients affected by SCCAC (Lukan 2009). In addition, it was recently tested in stage I-III SCCAC in association with cisplatin plus 5-FU and radiotherapy. Despite not reaching their pre-specified endpoints both studies reported an interesting activity in local control of disease, leading to hypothesize that cetuximab warrant further investigation in new strategies (Garg 2017, Sparano 2017);~Anti-PD1 treatments such as nivolumab and pembrolizumab showed promising activity in metastatic refractory SCCAC in terms of response rate and disease control with acceptable toxicity profiles (Morris 2017, Ott 2017);~The induction of immunogenic cell death was recently shown for cetuximab-based regimens (Pozzi 2016) and PD-L1 blockade should lead to NK cells activation enhancing cetuximab ADCC (Concha-Benavente 2015, Concha-Benavente 2016).~On the basis of these considerations, the investigators designed the present randomized phase II trial of avelumab alone or avelumab plus cetuximab for previously treated unresectable locally advanced or metastatic SCCAC.
|
Randomized Phase 2 Trial of Cetuximab and Avelumab or Avelumab Alone for Unresectable, Locally Advanced or Metastatic Squamous Cell Anal Carcinoma (SCCAC) Progressed After at Least One Line of Systemic Treatment
|
Squamous Cell Anal Carcinoma
|
* Drug: Avelumab
* Drug: Cetuximab
|
Inclusion Criteria:~Histologically proven diagnosis of SCCAC;~Progression on or after first line systemic therapy for surgically unresectable or metastatic disease. Systemic radiosensitizing chemotherapy with curative intent in limited-stage disease should be considered equal to a first line for a patient experiencing progression during or within 6 months of completion;~Evaluable disease lesion according to RECIST v1.1 criteria;~Availability of tumor sample (primary and/or metastatic sites);~Age ≥ 18 years;~Eastern Cooperative Oncology Group - Performance Status (ECOG PS) ≤ 2;~Life expectancy of at least 12 weeks;~Laboratory Requirements:~Neutrophils ≥ 1.5 x 109 /L; Platelets ≥ 100 x 109 /L; Hemoglobin ≥ 9 g/dL; Total bilirubin ≤ 1.5 time the upper-normal limits (UNL) of the normal values and ASAT (SGOT) and/or ALAT (SGPT) ≤ 2.5 x UNL (or <5 x UNL in case of liver metastases); Alkaline phosphatase ≤ 2.5 x UNL (or <5 x UNL in case of liver metastases); Creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method) or serum creatinine ≤1.5 x UNL;~HIV-positive patients are eligible if their CD4+ cell count amounts to 300 cells per μL or more; HIV viral load has to be undetectable, and they have to be compliant with antiretroviral treatment;~Negative serum or urine pregnancy test at screening for women of childbearing potential. Female subjects, or male subjects with female partners of child-bearing potential must be willing to use highly effective contraception as approved by the investigator (i.e. barrier contraceptive measure or oral contraception, total abstinence) during the study and until 30 days after last study treatment;~Written informed consent to the study procedures and to molecular analyses before patients registration;~Will and ability to comply with the protocol.~Exclusion Criteria:~Previous therapy with any drug targeting T-cell co-regulatory proteins (i.e., immune checkpoint inhibitors);~Concurrent anticancer treatment or use of any investigational drug within 28 days before the start of the trial treatment;~Major surgical procedure, open biopsy, or significant traumatic injury occurred within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study;~History or evidence upon physical examination of CNS disease unless adequately treated. Patients with treated brain metastases are eligible if their lesions were stable and asymptomatic for at least 3 months;~Neutrophils < 1.5 x 109/L; Platelets < 100 x 109/L; Hemoglobin < 9 g/dL;~Active uncontrolled infections requiring systemic therapy or other clinically relevant concomitant illness contraindicating therapy administration or putting the patient at high risk for treatment-related toxicities;~Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive);~Patients with active autoimmune disease or history of autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent or might potentially affect vital organ function, or require use of immunosuppressive treatment including chronic prolonged systemic corticosteroids (defined as corticosteroid use for ≥ 1 month). Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible;~Current use of immunosuppressive medication, EXCEPT for the following:~intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection);~Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent;~Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication);~Prior organ transplantation including allogenic stem-cell transplantation;~Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines;~Known severe hypersensitivity reactions to monoclonal antibodies, any history of anaphylaxis, or uncontrolled asthma;~Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication;~Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonia, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study;~Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade > 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable;~Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of localized basal and squamous cell carcinoma of the skin or cervical cancer in situ;~Pregnant or lactating women;~Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary endpoint is Objective Response Rate (ORR). | The primary endpoint is Objective Response Rate (ORR). ORR is defined as the percentage of patients, relative to the total of enrolled subjects, achieving a complete (CR) or partial (PR) response, according to Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 criteria. The determination of the radiological response will be based on the investigator's reported evaluation. | Radiological responses will be evaluated starting from cycle 1 day 1 of treatment until disease progression, withdrawal of consent or death for any reason, whichever occurs first assessed up to 12 moths. |
|
Cetuximab, Avelumab, Antineoplastic Agents, Immunological, Antineoplastic Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A (avelumab)<br>avelumab 10 mg/kg iv day 1; To be repeated every 2 weeks (14 days) until progression of disease, refuse or inacceptable toxicity. | Drug: Avelumab<br>* avelumab 10 mg/kg iv day 1; To be repeated every 2 weeks (14 days) until progression of disease, refuse or inacceptable toxicity.<br>|
| Experimental: B (cetuximab + avelumab)<br>cetuximab 500 mg/m2 plus avelumab 10 mg/kg iv day 1. To be repeated every 2 weeks (14 days) until progression of disease, refuse or inacceptable toxicity. | Drug: Avelumab<br>* avelumab 10 mg/kg iv day 1; To be repeated every 2 weeks (14 days) until progression of disease, refuse or inacceptable toxicity.<br>Drug: Cetuximab<br>* cetuximab 500 mg/m2 plus avelumab 10 mg/kg iv day 1. To be repeated every 2 weeks (14 days) until progression of disease, refuse or inacceptable toxicity.<br>|
|
Cetuximab + Avelumab or Avelumab Alone for Unresectable, Locally Advanced or Metastatic Squamous Cell Anal Carcinoma (SCCAC) Progressed After at Least One Line of Systemic Treatment (CARACAS)
Study Overview
=================
Brief Summary
-----------------
The standard first line treatment in SCCAC is the association of 5-FU with cisplatin reaching a percentage of survival at 5 years of about 32% (Faivre 1999); in a recent case series of patients affected by SCCAC, the combination of 5-FU and cisplatin as first line treatment produced 34.4% objective response rate (ORR) and a 5 years survival rate of 15% (Sclafani 2017); No standard second line treatment exists for SCCAC; Cetuximab in association with irinotecan has demonstrated promising results in pretreated patients affected by SCCAC (Lukan 2009). In addition, it was recently tested in stage I-III SCCAC in association with cisplatin plus 5-FU and radiotherapy. Despite not reaching their pre-specified endpoints both studies reported an interesting activity in local control of disease, leading to hypothesize that cetuximab warrant further investigation in new strategies (Garg 2017, Sparano 2017); Anti-PD1 treatments such as nivolumab and pembrolizumab showed promising activity in metastatic refractory SCCAC in terms of response rate and disease control with acceptable toxicity profiles (Morris 2017, Ott 2017); The induction of immunogenic cell death was recently shown for cetuximab-based regimens (Pozzi 2016) and PD-L1 blockade should lead to NK cells activation enhancing cetuximab ADCC (Concha-Benavente 2015, Concha-Benavente 2016). On the basis of these considerations, the investigators designed the present randomized phase II trial of avelumab alone or avelumab plus cetuximab for previously treated unresectable locally advanced or metastatic SCCAC.
Official Title
-----------------
Randomized Phase 2 Trial of Cetuximab and Avelumab or Avelumab Alone for Unresectable, Locally Advanced or Metastatic Squamous Cell Anal Carcinoma (SCCAC) Progressed After at Least One Line of Systemic Treatment
Conditions
-----------------
Squamous Cell Anal Carcinoma
Intervention / Treatment
-----------------
* Drug: Avelumab
* Drug: Cetuximab
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically proven diagnosis of SCCAC; Progression on or after first line systemic therapy for surgically unresectable or metastatic disease. Systemic radiosensitizing chemotherapy with curative intent in limited-stage disease should be considered equal to a first line for a patient experiencing progression during or within 6 months of completion; Evaluable disease lesion according to RECIST v1.1 criteria; Availability of tumor sample (primary and/or metastatic sites); Age ≥ 18 years; Eastern Cooperative Oncology Group - Performance Status (ECOG PS) ≤ 2; Life expectancy of at least 12 weeks; Laboratory Requirements: Neutrophils ≥ 1.5 x 109 /L; Platelets ≥ 100 x 109 /L; Hemoglobin ≥ 9 g/dL; Total bilirubin ≤ 1.5 time the upper-normal limits (UNL) of the normal values and ASAT (SGOT) and/or ALAT (SGPT) ≤ 2.5 x UNL (or <5 x UNL in case of liver metastases); Alkaline phosphatase ≤ 2.5 x UNL (or <5 x UNL in case of liver metastases); Creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method) or serum creatinine ≤1.5 x UNL; HIV-positive patients are eligible if their CD4+ cell count amounts to 300 cells per μL or more; HIV viral load has to be undetectable, and they have to be compliant with antiretroviral treatment; Negative serum or urine pregnancy test at screening for women of childbearing potential. Female subjects, or male subjects with female partners of child-bearing potential must be willing to use highly effective contraception as approved by the investigator (i.e. barrier contraceptive measure or oral contraception, total abstinence) during the study and until 30 days after last study treatment; Written informed consent to the study procedures and to molecular analyses before patients registration; Will and ability to comply with the protocol. Exclusion Criteria: Previous therapy with any drug targeting T-cell co-regulatory proteins (i.e., immune checkpoint inhibitors); Concurrent anticancer treatment or use of any investigational drug within 28 days before the start of the trial treatment; Major surgical procedure, open biopsy, or significant traumatic injury occurred within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study; History or evidence upon physical examination of CNS disease unless adequately treated. Patients with treated brain metastases are eligible if their lesions were stable and asymptomatic for at least 3 months; Neutrophils < 1.5 x 109/L; Platelets < 100 x 109/L; Hemoglobin < 9 g/dL; Active uncontrolled infections requiring systemic therapy or other clinically relevant concomitant illness contraindicating therapy administration or putting the patient at high risk for treatment-related toxicities; Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive); Patients with active autoimmune disease or history of autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent or might potentially affect vital organ function, or require use of immunosuppressive treatment including chronic prolonged systemic corticosteroids (defined as corticosteroid use for ≥ 1 month). Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible; Current use of immunosuppressive medication, EXCEPT for the following: intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication); Prior organ transplantation including allogenic stem-cell transplantation; Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines; Known severe hypersensitivity reactions to monoclonal antibodies, any history of anaphylaxis, or uncontrolled asthma; Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication; Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonia, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study; Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade > 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable; Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of localized basal and squamous cell carcinoma of the skin or cervical cancer in situ; Pregnant or lactating women; Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A (avelumab)<br>avelumab 10 mg/kg iv day 1; To be repeated every 2 weeks (14 days) until progression of disease, refuse or inacceptable toxicity. | Drug: Avelumab<br>* avelumab 10 mg/kg iv day 1; To be repeated every 2 weeks (14 days) until progression of disease, refuse or inacceptable toxicity.<br>|
| Experimental: B (cetuximab + avelumab)<br>cetuximab 500 mg/m2 plus avelumab 10 mg/kg iv day 1. To be repeated every 2 weeks (14 days) until progression of disease, refuse or inacceptable toxicity. | Drug: Avelumab<br>* avelumab 10 mg/kg iv day 1; To be repeated every 2 weeks (14 days) until progression of disease, refuse or inacceptable toxicity.<br>Drug: Cetuximab<br>* cetuximab 500 mg/m2 plus avelumab 10 mg/kg iv day 1. To be repeated every 2 weeks (14 days) until progression of disease, refuse or inacceptable toxicity.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary endpoint is Objective Response Rate (ORR). | The primary endpoint is Objective Response Rate (ORR). ORR is defined as the percentage of patients, relative to the total of enrolled subjects, achieving a complete (CR) or partial (PR) response, according to Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 criteria. The determination of the radiological response will be based on the investigator's reported evaluation. | Radiological responses will be evaluated starting from cycle 1 day 1 of treatment until disease progression, withdrawal of consent or death for any reason, whichever occurs first assessed up to 12 moths. |
|
|||
NCT03327922
|
Interrupted Subdermal Suture Spacing During Linear Wound Closures and the Effect on Wound Cosmesis
|
This study aims to investigate whether the spacing of the interrupted deep (subdermal) sutures affects surgical wound cosmesis on the trunk and extremities. In other words, the investigator would like to determine which of the following yields a more cosmetically appealing scar: many closely approximated subdermal sutures or fewer, more widely spaced subdermal sutures. The investigator wishes to compare the effects of one versus two centimeter spacing between sutures.
|
Sutures are the standard of care in repairing cutaneous wounds. The majority of surgical reconstructions following a Mohs micrographic surgery and standard surgical excisions require two layers of sutures: a deep layer and a top layer. The deep layer dissolves naturally whereas the top layer must be removed.~This study aims to investigate whether the spacing of the interrupted deep (subdermal) sutures affects surgical wound cosmesis on the trunk and extremities. In other words, the investigator would like to determine which of the following yields a more cosmetically appealing scar: many closely approximated subdermal sutures or fewer, more widely spaced subdermal sutures. The investigator wishes to compare the effects of one versus two centimeter spacing between sutures. It is possible that fewer, more widely spaced sutures may leave more open space in the wound, leaving more tension to pull on those few sutures, possibly encouraging the wound to dehisce and make it harder to approximate the wound edges yielding a less cosmetically appealing scar compared to placing many closely approximated sutures which would decrease the tension and likely better approximate the wound edges yielding a more cosmetically appealing scar. On the other hand, we may find that suture spacing has no effect on wound cosmesis and that placing fewer, more widely spaced sutures is much more time efficient. The investigator may also find that the effect of suture spacing on wound cosmesis is dependent on wound tension. For example, perhaps the suture pacing would have no effect on the cosmesis of a wound under no tension, however, for a wound under high tension, it is possible that many closely approximated sutures would yield better cosmetic results for the reasons listed above.
|
Interrupted Subdermal Suture Spacing During Linear Wound Closures and the Effect on Wound Cosmesis: a Randomized Evaluator Blinded Split Wound Comparative Effectiveness Trial
|
Interrupted Subdermal Suture
|
* Device: Vicryl absorbable suture
|
Inclusion Criteria:~18 years of age or older~Able to give informed consent themselves~Patient scheduled for cutaneous surgical procedure on the trunk and extremities with predicted primary closure~Willing to return for follow up visit.~Exclusion Criteria:~Mentally handicapped~Unable to understand written and oral English~Incarceration~Under 18 years of age~Pregnant Women~Wounds with predicted closure length less than 4 cm
|
18 Years
| null |
All
|
No
|
Primary Purpose: Other
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: At the follow-up visit, two blinded observers will record their scores independently using the physician observer scar assessment score instrument (POSAS).
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Scar Assessment | The primary endpoint will be the score of two blinded reviewers using the patient observer scar assessment score. | 3 months following procedure |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Width of Scar | A secondary endpoint will include the width of the scar 1 cm from midline on each side | 3 months following procedure |
| Erythema | If one half of the scar has more associated erythema, this will be noted | 3 months following procedure |
|
Subdermal, Suture, Wound Closure, Wound Cosmesis
|
Wounds and Injuries
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vicryl absorbable suture placed 2 cm apart<br>Wound closed with sutures spaced 2 centimeters apart will be treated in a simple, interrupted subdermal suture pattern | Device: Vicryl absorbable suture<br>* Vicryl absorbable suture is a synthetic sterile surgical suture made up of a copolymer<br>|
| Experimental: Vicryl absorbable suture placed 1 cm apart<br>Wound closed with sutures spaced 1 centimeter apart will be treated in a simple, interrupted subdermal suture pattern | Device: Vicryl absorbable suture<br>* Vicryl absorbable suture is a synthetic sterile surgical suture made up of a copolymer<br>|
|
Interrupted Subdermal Suture Spacing During Linear Wound Closures and the Effect on Wound Cosmesis
Study Overview
=================
Brief Summary
-----------------
This study aims to investigate whether the spacing of the interrupted deep (subdermal) sutures affects surgical wound cosmesis on the trunk and extremities. In other words, the investigator would like to determine which of the following yields a more cosmetically appealing scar: many closely approximated subdermal sutures or fewer, more widely spaced subdermal sutures. The investigator wishes to compare the effects of one versus two centimeter spacing between sutures.
Detailed Description
-----------------
Sutures are the standard of care in repairing cutaneous wounds. The majority of surgical reconstructions following a Mohs micrographic surgery and standard surgical excisions require two layers of sutures: a deep layer and a top layer. The deep layer dissolves naturally whereas the top layer must be removed. This study aims to investigate whether the spacing of the interrupted deep (subdermal) sutures affects surgical wound cosmesis on the trunk and extremities. In other words, the investigator would like to determine which of the following yields a more cosmetically appealing scar: many closely approximated subdermal sutures or fewer, more widely spaced subdermal sutures. The investigator wishes to compare the effects of one versus two centimeter spacing between sutures. It is possible that fewer, more widely spaced sutures may leave more open space in the wound, leaving more tension to pull on those few sutures, possibly encouraging the wound to dehisce and make it harder to approximate the wound edges yielding a less cosmetically appealing scar compared to placing many closely approximated sutures which would decrease the tension and likely better approximate the wound edges yielding a more cosmetically appealing scar. On the other hand, we may find that suture spacing has no effect on wound cosmesis and that placing fewer, more widely spaced sutures is much more time efficient. The investigator may also find that the effect of suture spacing on wound cosmesis is dependent on wound tension. For example, perhaps the suture pacing would have no effect on the cosmesis of a wound under no tension, however, for a wound under high tension, it is possible that many closely approximated sutures would yield better cosmetic results for the reasons listed above.
Official Title
-----------------
Interrupted Subdermal Suture Spacing During Linear Wound Closures and the Effect on Wound Cosmesis: a Randomized Evaluator Blinded Split Wound Comparative Effectiveness Trial
Conditions
-----------------
Interrupted Subdermal Suture
Intervention / Treatment
-----------------
* Device: Vicryl absorbable suture
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18 years of age or older Able to give informed consent themselves Patient scheduled for cutaneous surgical procedure on the trunk and extremities with predicted primary closure Willing to return for follow up visit. Exclusion Criteria: Mentally handicapped Unable to understand written and oral English Incarceration Under 18 years of age Pregnant Women Wounds with predicted closure length less than 4 cm
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Other
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: At the follow-up visit, two blinded observers will record their scores independently using the physician observer scar assessment score instrument (POSAS).
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vicryl absorbable suture placed 2 cm apart<br>Wound closed with sutures spaced 2 centimeters apart will be treated in a simple, interrupted subdermal suture pattern | Device: Vicryl absorbable suture<br>* Vicryl absorbable suture is a synthetic sterile surgical suture made up of a copolymer<br>|
| Experimental: Vicryl absorbable suture placed 1 cm apart<br>Wound closed with sutures spaced 1 centimeter apart will be treated in a simple, interrupted subdermal suture pattern | Device: Vicryl absorbable suture<br>* Vicryl absorbable suture is a synthetic sterile surgical suture made up of a copolymer<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Scar Assessment | The primary endpoint will be the score of two blinded reviewers using the patient observer scar assessment score. | 3 months following procedure |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Width of Scar | A secondary endpoint will include the width of the scar 1 cm from midline on each side | 3 months following procedure |
| Erythema | If one half of the scar has more associated erythema, this will be noted | 3 months following procedure |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Subdermal, Suture, Wound Closure, Wound Cosmesis
|
NCT01267201
|
A Study Comparing Drug Availability Of Methylprednisolone In Liquid Form Versus Methylprednisolone In Tablet Form
|
A new formulation of methylprednisolone is being developed. A study is needed to determine the drug availability using the new formulation, a powder for reconstitution into a suspension, versus the current commercially available tablet formulation in healthy volunteers.
|
A Phase 1, Open-Label, Randomized, Single-Dose, 3-Treatment, Crossover Bioavailability Study Comparing Constituted Methylprednisolone Powder For Oral Suspension 4 Mg/Ml to Methylprednisolone 32 Mg Tablet Under Fasted Conditions
|
Biological Availability
|
* Drug: methylprednisolone
* Drug: methylprednisolone
* Drug: methylprednisolone
|
Inclusion Criteria:~Body Mass Index (BMI) of 17.5 to 30.5 kg/m2;~a total body weight >45 kg (99 lbs).~Exclusion Criteria:~Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease;~Any condition possibly affecting drug absorption (eg, gastrectomy).
|
21 Years
|
55 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] | AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). | 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 12, 16 and 24 hours (hrs) post-dose |
| Maximum Observed Plasma Concentration (Cmax) | | 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 12, 16 and 24 hrs post-dose |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | | 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 12, 16 and 24 hrs post-dose |
| Plasma Decay Half-life (t1/2) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 12, 16 and 24 hrs post-dose |
|
Single dose bioavailability study of methylprednisolone powder for oral suspension (4mg/mL) versus methylprednisolone tablet (32 mg)
|
Prednisolone, Prednisolone acetate, Prednisolone hemisuccinate, Prednisolone phosphate, Anti-Inflammatory Agents, Antiemetics, Autonomic Agents, Peripheral Nervous System Agents, Gastrointestinal Agents, Methylprednisolone, Methylprednisolone Acetate, Methylprednisolone Hemisuccinate, Physiological Effects of Drugs, Glucocorticoids, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Neuroprotective Agents, Protective Agents, Antineoplastic Agents, Hormonal, Antineoplastic Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: POS formulation #1<br> | Drug: methylprednisolone<br>* powder for oral suspension 4 mg/mL single dose (8 mL)<br>|
| Experimental: POS formulation #2<br> | Drug: methylprednisolone<br>* powder for oral suspension 4 mg/mL singe dose (8 ml)<br>|
| Active Comparator: commercial tablet<br> | Drug: methylprednisolone<br>* tablet 32 mg single dose<br>|
|
A Study Comparing Drug Availability Of Methylprednisolone In Liquid Form Versus Methylprednisolone In Tablet Form
Study Overview
=================
Brief Summary
-----------------
A new formulation of methylprednisolone is being developed. A study is needed to determine the drug availability using the new formulation, a powder for reconstitution into a suspension, versus the current commercially available tablet formulation in healthy volunteers.
Official Title
-----------------
A Phase 1, Open-Label, Randomized, Single-Dose, 3-Treatment, Crossover Bioavailability Study Comparing Constituted Methylprednisolone Powder For Oral Suspension 4 Mg/Ml to Methylprednisolone 32 Mg Tablet Under Fasted Conditions
Conditions
-----------------
Biological Availability
Intervention / Treatment
-----------------
* Drug: methylprednisolone
* Drug: methylprednisolone
* Drug: methylprednisolone
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; a total body weight >45 kg (99 lbs). Exclusion Criteria: Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease; Any condition possibly affecting drug absorption (eg, gastrectomy).
Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 55 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: POS formulation #1<br> | Drug: methylprednisolone<br>* powder for oral suspension 4 mg/mL single dose (8 mL)<br>|
| Experimental: POS formulation #2<br> | Drug: methylprednisolone<br>* powder for oral suspension 4 mg/mL singe dose (8 ml)<br>|
| Active Comparator: commercial tablet<br> | Drug: methylprednisolone<br>* tablet 32 mg single dose<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] | AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). | 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 12, 16 and 24 hours (hrs) post-dose |
| Maximum Observed Plasma Concentration (Cmax) | | 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 12, 16 and 24 hrs post-dose |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | | 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 12, 16 and 24 hrs post-dose |
| Plasma Decay Half-life (t1/2) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 12, 16 and 24 hrs post-dose |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Single dose bioavailability study of methylprednisolone powder for oral suspension (4mg/mL) versus methylprednisolone tablet (32 mg)
|
|
NCT00628745
|
Transthyretin Amyloidosis Outcome Survey (THAOS)
|
THAOS is a global, multi-center, longitudinal observational survey open to all patients with transthyretin amyloidosis (ATTR), including ATTR-PN (polyneuropathy), ATTR-CM (cardiomyopathy) and wild-type ATTR-CM. It is open-ended with a minimum duration of 10 years. Patients will be followed as long as they are able to participate. The principal aims of this outcome survey are to better understand and characterize the natural history of the disease by studying a large and heterogenous patient population. Survey data may be used to develop new treatment guidelines and recommendations, and to inform and educate clinicians about the management of this disease.
|
n/a NA
|
Transthyretin Amyloidosis Outcomes Survey (THAOS): A Global, Multi-Center, Longitudinal, Observational Survey of Patients With Documented Transthyretin Gene Mutations or Wild-Type Transthyretin Amyloidosis.
|
Transthyretin Gene Mutations, Transthyretin Amyloidosis
|
* Other: None. Observational Study.
|
Inclusion Criteria: Patients must meet all of the following inclusion criteria to be eligible for inclusion into THAOS:~Evidence of a personally signed and dated informed consent document indicating that the participant (or a legally acceptable representative) has been informed of all pertinent aspects of the study.~Males and females greater than or equal to 18 years of age.~Confirmed genotyped TTR mutation with or without a diagnosis of hereditary or wild-type ATTR amyloidosis. Confirmation of ATTRwt amyloidosis will be determined by genotyped confirmation that patient does not possess a known mutation in TTR gene (ie, is a carrier of wild-type allele only) via genetic testing and one of the following set of criteria (a, b, or c):~Presence of amyloid in cardiac biopsy tissue confirmed as TTR amyloid by mass spectrometry or immunohistochemistry; or~Evidence of cardiac involvement by echocardiogram as defined by left ventricle wall thickness of >12 mm, and presence of amyloid in non-cardiac tissue confirmed as TTR amyloid by mass spectrometry or immunohistochemistry; or~Evidence of cardiac involvement by echocardiogram as defined by left ventricle wall thickness of >12 mm, and presence of amyloid in cardiac tissue indirectly confirmed by scintigraphy with a bone seeking tracer eg, 99mTC-DPD [99mTC-3,3-diphosphono-1,2-propano-dicarboxylic acid], 99mTC- PYP [Pyrophosphate], and 99mTC-HMDP [hydroxymethylene diphosphonate] with Perugini grade greater than or equal to 2.~Exclusion Criteria~Patients meeting any of the following will not be included in the study:~1. Patient has evidence of primary (light chain) or secondary amyloidosis.
|
18 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The objectives of THAOS are to describe the population of patients affected with TTR amyloidosis and to enhance the understanding of the disease natural history, including the variability and progression of the hereditary and acquired forms of disease. | Cardiovascular and Neurological efficacy endpoints for analysis of clinical outcomes on all enrolled patients with available data. Outcomes will be examined for the entire patient group, as well as through subgroups based on important variables. | Dec 2007 to June 2023 |
|
TRANSTHYRETIN, AMYLOIDOSIS, TRANSTHYRETIN AMYLOIDOSIS, Transthyretin amyloid cardiomyopathy
|
Neuromuscular Diseases, Genetic Diseases, Inborn, Amyloidosis, Familial, Metabolism, Inborn Errors, Amyloid Neuropathies, Familial, Amyloidosis, Proteostasis Deficiencies, Metabolic Diseases, Heredodegenerative Disorders, Nervous System, Neurodegenerative Diseases, Nervous System Diseases, Amyloid Neuropathies, Peripheral Nervous System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Observational<br> | Other: None. Observational Study.<br> <br> |
|
Transthyretin Amyloidosis Outcome Survey (THAOS)
Study Overview
=================
Brief Summary
-----------------
THAOS is a global, multi-center, longitudinal observational survey open to all patients with transthyretin amyloidosis (ATTR), including ATTR-PN (polyneuropathy), ATTR-CM (cardiomyopathy) and wild-type ATTR-CM. It is open-ended with a minimum duration of 10 years. Patients will be followed as long as they are able to participate. The principal aims of this outcome survey are to better understand and characterize the natural history of the disease by studying a large and heterogenous patient population. Survey data may be used to develop new treatment guidelines and recommendations, and to inform and educate clinicians about the management of this disease.
Detailed Description
-----------------
n/a NA
Official Title
-----------------
Transthyretin Amyloidosis Outcomes Survey (THAOS): A Global, Multi-Center, Longitudinal, Observational Survey of Patients With Documented Transthyretin Gene Mutations or Wild-Type Transthyretin Amyloidosis.
Conditions
-----------------
Transthyretin Gene Mutations, Transthyretin Amyloidosis
Intervention / Treatment
-----------------
* Other: None. Observational Study.
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients must meet all of the following inclusion criteria to be eligible for inclusion into THAOS: Evidence of a personally signed and dated informed consent document indicating that the participant (or a legally acceptable representative) has been informed of all pertinent aspects of the study. Males and females greater than or equal to 18 years of age. Confirmed genotyped TTR mutation with or without a diagnosis of hereditary or wild-type ATTR amyloidosis. Confirmation of ATTRwt amyloidosis will be determined by genotyped confirmation that patient does not possess a known mutation in TTR gene (ie, is a carrier of wild-type allele only) via genetic testing and one of the following set of criteria (a, b, or c): Presence of amyloid in cardiac biopsy tissue confirmed as TTR amyloid by mass spectrometry or immunohistochemistry; or Evidence of cardiac involvement by echocardiogram as defined by left ventricle wall thickness of >12 mm, and presence of amyloid in non-cardiac tissue confirmed as TTR amyloid by mass spectrometry or immunohistochemistry; or Evidence of cardiac involvement by echocardiogram as defined by left ventricle wall thickness of >12 mm, and presence of amyloid in cardiac tissue indirectly confirmed by scintigraphy with a bone seeking tracer eg, 99mTC-DPD [99mTC-3,3-diphosphono-1,2-propano-dicarboxylic acid], 99mTC- PYP [Pyrophosphate], and 99mTC-HMDP [hydroxymethylene diphosphonate] with Perugini grade greater than or equal to 2. Exclusion Criteria Patients meeting any of the following will not be included in the study: 1. Patient has evidence of primary (light chain) or secondary amyloidosis.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Observational<br> | Other: None. Observational Study.<br> <br> |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The objectives of THAOS are to describe the population of patients affected with TTR amyloidosis and to enhance the understanding of the disease natural history, including the variability and progression of the hereditary and acquired forms of disease. | Cardiovascular and Neurological efficacy endpoints for analysis of clinical outcomes on all enrolled patients with available data. Outcomes will be examined for the entire patient group, as well as through subgroups based on important variables. | Dec 2007 to June 2023 |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
TRANSTHYRETIN, AMYLOIDOSIS, TRANSTHYRETIN AMYLOIDOSIS, Transthyretin amyloid cardiomyopathy
|
||
NCT00895739
|
Alemtuzumab and Low-Dose Cyclosporine in Treating Patients With Severe Aplastic Anemia or Acquired Marrow Failure
|
RATIONALE: Immunosuppressive therapies, such as alemtuzumab and cyclosporine, may improve bone marrow function and increase blood cell counts. Giving alemtuzumab together with cyclosporine may be an effective treatment for severe aplastic anemia or acquired marrow failure.~PURPOSE: This phase II trial is studying the side effects of giving alemtuzumab together with cyclosporine and to see how well it works in treating patients with severe aplastic anemia or acquired marrow failure.
|
OBJECTIVES:~Primary~Determine the safety of alemtuzumab and low-dose cyclosporine, as defined by occurrence of adverse effects, in patients with severe aplastic anemia or single lineage acquired marrow failure.~Determine the efficacy of this regimen, in terms of overall survival, hematological response (partial and complete response, including time to response) and failure-free survival (failure is defined as no response, chronic treatment-maintained response, or relapse), in these patients.~Secondary~Evaluate the incidence of adverse effects after treatment.~Evaluate the long-term safety of alemtuzumab treatment.~Determine the time to achieve a complete hematological response.~Determine the proportion of patients maintaining hematological response free of any treatment.~Determine the incidence of relapse in responding patients.~Determine the incidence of severe infections.~Determine the requirement for IV antibiotics and antifungal therapy.~Determine the requirement for red cell and platelet transfusion.~Determine the incidence of CMV reactivation.~Determine the kinetics of immune reconstitution.~Determine the incidence of paroxysmal nocturnal hemoglobinuria clone (lymphoid or myeloid) development.~Determine the incidence of clonal evolution (i.e., karyotypic abnormalities or secondary myelodysplasia/leukemia).~OUTLINE: Patients receive alemtuzumab subcutaneously on days 1-5*. Patients also receive oral cyclosporine beginning on day 7 and continuing for ≥ 180 days, followed by a taper according to clinical condition.~NOTE: *Patients with single lineage aquired marrow failure receive alemtuzumab on days 1-4.~After completion of study therapy, patients will be followed up every 3 months for up to 2 years.
|
Alemtuzumab and Low-Dose Cyclosporine-A as Alternative Immunosuppressive Treatment for Severe Aplastic Anemia (SAA) and Single-Lineage Aplastic Patients
|
Nonmalignant Neoplasm
|
* Biological: alemtuzumab
* Drug: cyclosporine
|
DISEASE CHARACTERISTICS:~Diagnosis of 1 of the following:~Severe or very severe aplastic anemia, as defined by the following criteria:~Meets ≥ 2 of the following criteria:~Absolute neutrophil count < 0.5 x 10^9/L (severe) or < 0.2 x 10^9/L (very severe)~Platelet count < 20 x 10^9/L~Reticulocyte count < 20 x 10^9/L~Hypocellular bone marrow (< 30% cellularity) without evidence of fibrosis or malignant cells~Single lineage acquired marrow failure (e.g., pure red cell aplasia, agranulocytosis, amegakaryocytic thrombocytopenia)~Paroxysmal nocturnal hemoglobinuria clone allowed~Failed first-line therapy with antithymocyte globulin (ATG) and cyclosporine OR not eligible for ATG-based studies~Failure is defined as lack of hematological response, requirement for chronic immunosuppressive treatment to sustain response, or relapse~Not eligible for a low-risk stem cell transplantation~No evidence of risky myelodysplastic syndromes (i.e., IPSS 3-4), as defined by the presence of marrow blast excess or karyotypic abnormalities, or other primitive marrow disease~No history of constitutional aplastic anemia (e.g., Fanconi anemia or dyskeratosis congenita)~PATIENT CHARACTERISTICS:~WHO performance status 0-2~Not pregnant or nursing~No active malignant tumor within the past 5 years~Transaminases ≤ 3 times upper limit of normal (ULN)~Albumin ≥ 1.5 g/L~Creatinine ≤ 3 times ULN~No CMV viremia, as defined by positive PCR or pp65 test~No cardiac failure (i.e., ejection fraction < 35%)~No other concurrent life-threatening disease (including HIV infection)~PRIOR CONCURRENT THERAPY:~No prior allogeneic stem cell transplantation~At least 2 weeks since prior cyclosporine or filgrastim (G-CSF)
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Non-Randomized
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety, as defined by occurrence of adverse effects | | |
| Overall survival | | |
| Hematologic response (partial and complete response, including time to response) | | |
| Failure-free survival (failure is defined as no response, chronic treatment-maintained response, or relapse) | | |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse effects after treatment | | |
| Long-term safety of alemtuzumab treatment | | |
| Time to achieve a complete hematological response | | |
| Proportion of patients maintaining hematological response free of any treatment | | |
| Incidence of relapse in responding patients | | |
| Incidence of severe infections | | |
| Requirement for IV antibiotics and antifungal therapy | | |
| Requirement for red cell and platelet transfusion | | |
| Incidence of CMV reactivation | | |
| Kinetics of immune reconstitution | | |
| Incidence of paroxysmal nocturnal hemoglobinuria (PNH) clone (lymphoid or myeloid) development | | |
| Incidence of clonal evolution (i.e., karyotypic abnormalities or secondary myelodysplasia/leukemia) | | |
|
aplastic anemia
|
Calcineurin Inhibitors, Cyclosporine, Alemtuzumab, Cyclosporins, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action, Immunosuppressive Agents, Immunologic Factors, Physiological Effects of Drugs, Antifungal Agents, Anti-Infective Agents, Dermatologic Agents, Antirheumatic Agents, Antineoplastic Agents, Immunological, Antineoplastic Agents
|
| Intervention/Treatment |
| --- |
|Biological: alemtuzumab|nan|
|Drug: cyclosporine|nan|
|
Alemtuzumab and Low-Dose Cyclosporine in Treating Patients With Severe Aplastic Anemia or Acquired Marrow Failure
Study Overview
=================
Brief Summary
-----------------
RATIONALE: Immunosuppressive therapies, such as alemtuzumab and cyclosporine, may improve bone marrow function and increase blood cell counts. Giving alemtuzumab together with cyclosporine may be an effective treatment for severe aplastic anemia or acquired marrow failure. PURPOSE: This phase II trial is studying the side effects of giving alemtuzumab together with cyclosporine and to see how well it works in treating patients with severe aplastic anemia or acquired marrow failure.
Detailed Description
-----------------
OBJECTIVES: Primary Determine the safety of alemtuzumab and low-dose cyclosporine, as defined by occurrence of adverse effects, in patients with severe aplastic anemia or single lineage acquired marrow failure. Determine the efficacy of this regimen, in terms of overall survival, hematological response (partial and complete response, including time to response) and failure-free survival (failure is defined as no response, chronic treatment-maintained response, or relapse), in these patients. Secondary Evaluate the incidence of adverse effects after treatment. Evaluate the long-term safety of alemtuzumab treatment. Determine the time to achieve a complete hematological response. Determine the proportion of patients maintaining hematological response free of any treatment. Determine the incidence of relapse in responding patients. Determine the incidence of severe infections. Determine the requirement for IV antibiotics and antifungal therapy. Determine the requirement for red cell and platelet transfusion. Determine the incidence of CMV reactivation. Determine the kinetics of immune reconstitution. Determine the incidence of paroxysmal nocturnal hemoglobinuria clone (lymphoid or myeloid) development. Determine the incidence of clonal evolution (i.e., karyotypic abnormalities or secondary myelodysplasia/leukemia). OUTLINE: Patients receive alemtuzumab subcutaneously on days 1-5*. Patients also receive oral cyclosporine beginning on day 7 and continuing for ≥ 180 days, followed by a taper according to clinical condition. NOTE: *Patients with single lineage aquired marrow failure receive alemtuzumab on days 1-4. After completion of study therapy, patients will be followed up every 3 months for up to 2 years.
Official Title
-----------------
Alemtuzumab and Low-Dose Cyclosporine-A as Alternative Immunosuppressive Treatment for Severe Aplastic Anemia (SAA) and Single-Lineage Aplastic Patients
Conditions
-----------------
Nonmalignant Neoplasm
Intervention / Treatment
-----------------
* Biological: alemtuzumab
* Drug: cyclosporine
Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Diagnosis of 1 of the following: Severe or very severe aplastic anemia, as defined by the following criteria: Meets ≥ 2 of the following criteria: Absolute neutrophil count < 0.5 x 10^9/L (severe) or < 0.2 x 10^9/L (very severe) Platelet count < 20 x 10^9/L Reticulocyte count < 20 x 10^9/L Hypocellular bone marrow (< 30% cellularity) without evidence of fibrosis or malignant cells Single lineage acquired marrow failure (e.g., pure red cell aplasia, agranulocytosis, amegakaryocytic thrombocytopenia) Paroxysmal nocturnal hemoglobinuria clone allowed Failed first-line therapy with antithymocyte globulin (ATG) and cyclosporine OR not eligible for ATG-based studies Failure is defined as lack of hematological response, requirement for chronic immunosuppressive treatment to sustain response, or relapse Not eligible for a low-risk stem cell transplantation No evidence of risky myelodysplastic syndromes (i.e., IPSS 3-4), as defined by the presence of marrow blast excess or karyotypic abnormalities, or other primitive marrow disease No history of constitutional aplastic anemia (e.g., Fanconi anemia or dyskeratosis congenita) PATIENT CHARACTERISTICS: WHO performance status 0-2 Not pregnant or nursing No active malignant tumor within the past 5 years Transaminases ≤ 3 times upper limit of normal (ULN) Albumin ≥ 1.5 g/L Creatinine ≤ 3 times ULN No CMV viremia, as defined by positive PCR or pp65 test No cardiac failure (i.e., ejection fraction < 35%) No other concurrent life-threatening disease (including HIV infection) PRIOR CONCURRENT THERAPY: No prior allogeneic stem cell transplantation At least 2 weeks since prior cyclosporine or filgrastim (G-CSF)
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Non-Randomized
Masking: None (Open Label)
Arms and Interventions
| Intervention/Treatment |
| --- |
|Biological: alemtuzumab|nan|
|Drug: cyclosporine|nan|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety, as defined by occurrence of adverse effects | | |
| Overall survival | | |
| Hematologic response (partial and complete response, including time to response) | | |
| Failure-free survival (failure is defined as no response, chronic treatment-maintained response, or relapse) | | |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse effects after treatment | | |
| Long-term safety of alemtuzumab treatment | | |
| Time to achieve a complete hematological response | | |
| Proportion of patients maintaining hematological response free of any treatment | | |
| Incidence of relapse in responding patients | | |
| Incidence of severe infections | | |
| Requirement for IV antibiotics and antifungal therapy | | |
| Requirement for red cell and platelet transfusion | | |
| Incidence of CMV reactivation | | |
| Kinetics of immune reconstitution | | |
| Incidence of paroxysmal nocturnal hemoglobinuria (PNH) clone (lymphoid or myeloid) development | | |
| Incidence of clonal evolution (i.e., karyotypic abnormalities or secondary myelodysplasia/leukemia) | | |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
aplastic anemia
|
NCT05079789
|
Amiloride in Nephrotic Syndrome
|
The AMILOR study compares treatment of edema in nephrotic syndrome with Amiloride vs. Furosemide.
|
The monocenter randomized-controlled AMILOR trial investigates the efficacy of the ENaC blocker amiloride in reducing edema in nephrotic syndrome compared with standard therapy with the loop diuretic furosemide.~Patients with acute nephrotic syndrome are randomized to receive amiloride (starting dose 5 mg) or furosemide (starting dose 40 mg) for 16 days. The target number of patients is n = 18 per arm. Exclusion criteria include GFR <30ml/min/1.73m², AKIN 1 and 2, hypotension, hyper-/ hypokalemia, and hyponatremia. Overhydration is quantified by bioimpedance spectroscopy. Depending on the course of overhydration, dose adjustments (day 2, 5, 8, 12) or addition of HCT (day 8) are performed during the course of the study.~Primary endpoint is decrease in overhydration at day 8, secondary endpoints include decrease in overhydration at day 16, as well as body weight, edema volume, blood pressure, urine volume, natriuresis at day 8 and 16, and need for dose adjustments and co-medication with HCT. Plasma potassium, sodium, and creatinine concentrations are measured as safety parameters.
|
Randomized, Controlled Interventional Trial to Investigate the Efficacy of Amiloride for the Treatment of Edema in Human Nephrotic Syndrome
|
Nephrotic Syndrome, Edema, Sodium Retention
|
* Drug: Amiloride
* Drug: Furosemide
|
Inclusion Criteria:~Acute nephrotic syndrome with proteinuria > 3 g/day and formation of edema.~Age ≥ 18 years at the time of signing the informed consent.~Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures.~Ability to adhere to the study visit schedule and other protocol requirements.~Use of adequate thrombosis prophylaxis due to the increased risk of thrombosis in nephrotic syndrome and the expected fluctuations in volume balance during study participation.~Subject (male or female) is willing to use highly effective methods of contraception according to the Clinical trial fertility group recommendations.~Female Patients of childbearing potential (WOCBP) must agree to pregnancy testing before inclusion in the study.~Female Patients must agree to abstain from breastfeeding during study participation and 28 days after study drug discontinuation.~All subjects must agree not to share medication.~Exclusion Criteria:~Severe reduction of kidney function: Creatinine clearance or calculated GFR < 30 mL/min/1.73m² or acute kidney injury KDIGO stage 2 or 3 or anuria.~Hypovolemia or dehydration.~Uncontrolled diabetes mellitus.~Hypotension, systolic blood pressure < 90 mmHg.~Hyperkalemia, plasma potassium concentration > 4.8 mmol/l.~Hypokalemia, plasma potassium concentration < 3.3 mmol/l.~Hyponatremia, plasma sodium concentration < 128 mmol/l.~Hypercalcemia, ionized calcium > 2.0 mmol/l or total albumin corrected calcium > 3.0 mmol/l.~Signs of cardiac decompensation (orthopnoe, dyspnoe NYHA IV).~Hepatic coma or precoma.~Symptoms of gout.~Current therapy with potassium-sparing diuretics (e.g. spironolactone) or potassium supplements.~Women during pregnancy and lactation.~History of hypersensitivity to the investigational medicinal product, comparator or co-medication or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product, comparator or co-medication.~Any other clinical condition that would jeopardize the patient's safety while participating in this clinical trial.~Active participation in other clinical trials or observation period of competing trials.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decrease of overhydration | Decrease of overhydration (OH) measured by bioimpedance spectroscopy | 8 days |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decrease of overhydration | Decrease of overhydration (OH) measured by bioimpedance spectroscopy | 16 days |
| Decrease of body weight | Decrease of body weight | 8 and 16 days |
| Decrease of edema cercumference | Decrease of edema cercumference, measured at the lower leg | 8 and 16 days |
| Decrease of blood pressure | Decrease of systolic and diastolic blood pressure | 8 and 16 days |
| Increase of urine volume and natriuresis | Increase of urine volume and natriuresis, measured in 24 hours collected urine | 8 and 16 days |
| Course of plasma renin activity and serum aldosterone concentration | Course of plasma renin activity and serum aldosterone concentration, measured in blood samples | 8 and 16 days |
| Changes of dose of study medication and need for co-medication | Number of required changes of dose of study medication and need for co-medication with HCT | 8 and 16 days |
| Occurrence of adverse events | Occurrence of adverse events | 16 days |
|
Nephrotic Syndrome, ENaC, Diuretic therapy, Amiloride, Proteasuria
|
Amiloride, Furosemide, Diuretics, Natriuretic Agents, Physiological Effects of Drugs, Sodium Potassium Chloride Symporter Inhibitors, Membrane Transport Modulators, Molecular Mechanisms of Pharmacological Action, Acid Sensing Ion Channel Blockers, Sodium Channel Blockers, Epithelial Sodium Channel Blockers, Diuretics, Potassium Sparing
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amiloride<br>Treatment wirh Amiloride, start dose 5 mg | Drug: Amiloride<br>* Treatment with amiloride, start dose 5 mg<br>|
| Active Comparator: Furosemide<br>Treatment with Furosemide, start dose 40 mg | Drug: Furosemide<br>* Treatment with furosemide, start dose 40 mg<br>|
|
Amiloride in Nephrotic Syndrome
Study Overview
=================
Brief Summary
-----------------
The AMILOR study compares treatment of edema in nephrotic syndrome with Amiloride vs. Furosemide.
Detailed Description
-----------------
The monocenter randomized-controlled AMILOR trial investigates the efficacy of the ENaC blocker amiloride in reducing edema in nephrotic syndrome compared with standard therapy with the loop diuretic furosemide. Patients with acute nephrotic syndrome are randomized to receive amiloride (starting dose 5 mg) or furosemide (starting dose 40 mg) for 16 days. The target number of patients is n = 18 per arm. Exclusion criteria include GFR <30ml/min/1.73m², AKIN 1 and 2, hypotension, hyper-/ hypokalemia, and hyponatremia. Overhydration is quantified by bioimpedance spectroscopy. Depending on the course of overhydration, dose adjustments (day 2, 5, 8, 12) or addition of HCT (day 8) are performed during the course of the study. Primary endpoint is decrease in overhydration at day 8, secondary endpoints include decrease in overhydration at day 16, as well as body weight, edema volume, blood pressure, urine volume, natriuresis at day 8 and 16, and need for dose adjustments and co-medication with HCT. Plasma potassium, sodium, and creatinine concentrations are measured as safety parameters.
Official Title
-----------------
Randomized, Controlled Interventional Trial to Investigate the Efficacy of Amiloride for the Treatment of Edema in Human Nephrotic Syndrome
Conditions
-----------------
Nephrotic Syndrome, Edema, Sodium Retention
Intervention / Treatment
-----------------
* Drug: Amiloride
* Drug: Furosemide
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Acute nephrotic syndrome with proteinuria > 3 g/day and formation of edema. Age ≥ 18 years at the time of signing the informed consent. Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures. Ability to adhere to the study visit schedule and other protocol requirements. Use of adequate thrombosis prophylaxis due to the increased risk of thrombosis in nephrotic syndrome and the expected fluctuations in volume balance during study participation. Subject (male or female) is willing to use highly effective methods of contraception according to the Clinical trial fertility group recommendations. Female Patients of childbearing potential (WOCBP) must agree to pregnancy testing before inclusion in the study. Female Patients must agree to abstain from breastfeeding during study participation and 28 days after study drug discontinuation. All subjects must agree not to share medication. Exclusion Criteria: Severe reduction of kidney function: Creatinine clearance or calculated GFR < 30 mL/min/1.73m² or acute kidney injury KDIGO stage 2 or 3 or anuria. Hypovolemia or dehydration. Uncontrolled diabetes mellitus. Hypotension, systolic blood pressure < 90 mmHg. Hyperkalemia, plasma potassium concentration > 4.8 mmol/l. Hypokalemia, plasma potassium concentration < 3.3 mmol/l. Hyponatremia, plasma sodium concentration < 128 mmol/l. Hypercalcemia, ionized calcium > 2.0 mmol/l or total albumin corrected calcium > 3.0 mmol/l. Signs of cardiac decompensation (orthopnoe, dyspnoe NYHA IV). Hepatic coma or precoma. Symptoms of gout. Current therapy with potassium-sparing diuretics (e.g. spironolactone) or potassium supplements. Women during pregnancy and lactation. History of hypersensitivity to the investigational medicinal product, comparator or co-medication or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product, comparator or co-medication. Any other clinical condition that would jeopardize the patient's safety while participating in this clinical trial. Active participation in other clinical trials or observation period of competing trials.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amiloride<br>Treatment wirh Amiloride, start dose 5 mg | Drug: Amiloride<br>* Treatment with amiloride, start dose 5 mg<br>|
| Active Comparator: Furosemide<br>Treatment with Furosemide, start dose 40 mg | Drug: Furosemide<br>* Treatment with furosemide, start dose 40 mg<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decrease of overhydration | Decrease of overhydration (OH) measured by bioimpedance spectroscopy | 8 days |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decrease of overhydration | Decrease of overhydration (OH) measured by bioimpedance spectroscopy | 16 days |
| Decrease of body weight | Decrease of body weight | 8 and 16 days |
| Decrease of edema cercumference | Decrease of edema cercumference, measured at the lower leg | 8 and 16 days |
| Decrease of blood pressure | Decrease of systolic and diastolic blood pressure | 8 and 16 days |
| Increase of urine volume and natriuresis | Increase of urine volume and natriuresis, measured in 24 hours collected urine | 8 and 16 days |
| Course of plasma renin activity and serum aldosterone concentration | Course of plasma renin activity and serum aldosterone concentration, measured in blood samples | 8 and 16 days |
| Changes of dose of study medication and need for co-medication | Number of required changes of dose of study medication and need for co-medication with HCT | 8 and 16 days |
| Occurrence of adverse events | Occurrence of adverse events | 16 days |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Nephrotic Syndrome, ENaC, Diuretic therapy, Amiloride, Proteasuria
|
NCT00006942
|
Bryostatin 1 and Cisplatin in Treating Patients With Advanced Recurrent or Residual Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer
|
Phase II trial to study the effectiveness of combining bryostatin 1 and cisplatin in treating patients who have advanced recurrent or residual ovarian epithelial, fallopian tube, or primary peritoneal cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.
|
PRIMARY OBJECTIVES:~I. To estimate the overall response rate and the complete response rate of patients with platinum-refractory ovarian cancer who are treated with infusional Bryostatin-1 given in combination with intravenous cisplatin.~II. To estimate the duration of response in these patients. III. To obtain tissue in order to evaluate the molecular determinants of apoptosis including: p53 status, WAF1/CIP1 gene expression prior to and directly after chemotherapy, bcl-2 gene expression in vivo, bcl-2/bax ratio, p21, and the extent of apoptosis determined by the TdT assay; and the molecular determinants of DNA damage and repair including: expression levels of ERCC1.~OUTLINE: This is a multicenter study.~Patients receive bryostatin 1 IV continuously over 72 hours immediately followed by cisplatin IV over 1 hour. Treatment continues every 3 weeks for a minimum of 2 courses in the absence of disease progression.~Patients are followed for survival.~PROJECTED ACCRUAL: A total of 18-32 patients will be accrued for this study within 2 years.
|
A Phase II Trial of Bryostatin in Combination With Cisplatin in Patients With Recurrent or Persistent Epithelial Ovarian Cancer
|
Fallopian Tube Cancer, Primary Peritoneal Cavity Cancer, Recurrent Ovarian Epithelial Cancer, Stage III Ovarian Epithelial Cancer, Stage IV Ovarian Epithelial Cancer
|
* Drug: bryostatin 1
* Drug: cisplatin
* Other: laboratory biomarker analysis
|
Inclusion Criteria:~Advanced recurrent or residual ovarian, fallopian tube, or papillary primary peritoneal cancer which has been histologically confirmed~Eligible patients include patients with measurable disease who have progressed while on chemotherapeutic treatment, patients with biopsy-proven persistent, clinically-measurable disease with best response as stable at the completion of planned first-line therapy, patients with persistent or recurrent disease with rising CA-125 to levels at least twice normal; the CA-125 increase must be documented by two independent measurements; no patient may have received more than two prior regimens of chemotherapy including first-line treatment~Patients must have a Karnofsky performance status of greater than or equal to 50% and an estimated survival of at least three months~Measured or calculated clearance >= 60 ml/min~AGC >= 1800/mm^3~Plts >= 100,000/mm^3~Bilirubin =< 1.5 mg/dl~SGOT less than 2 x upper limit of normal~Previous radiotherapy or chemotherapy must have been completed at least three weeks before treatment under this protocol~Patients must have the ability to give voluntary informed consent and to comply with the treatment and required tests~Because Bryostatin is of unknown teratogenic potential, women of childbearing potential must have a negative pregnancy test and must take adequate precautions to prevent pregnancy during treatment~Patients with any non-malignant intercurrent illness (e.g. cardiovascular, pulmonary, or central nervous system disease) which is either poorly controlled with currently available treatment, or is of such severity that the investigators deem it unwise to enter the patient on protocol shall be ineligible~Patients currently being treated for severe infection or who are recovering from major surgery are ineligible until recovery is deemed complete by the investigator~The extent of all evaluable and nonevaluable disease must be documented; pretreatment radiographic examinations should be done no earlier than 4 weeks (28 days) prior to the first course of chemotherapy; pre-treatment chemistries and CA-125 levels should be done no earlier than two weeks (14 days) prior to initiation of chemotherapy; (in calculating days of tests and measurements, the day a test or measurement is done is considered day 0; therefore, if a test is done on Monday, the Monday four weeks later would be considered day 28; this allows for efficient patient scheduling without exceeding the guidelines)
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | | Time from first day of treatment to time of death due to any cause, assessed up to 9 years |
| Progression-free survival | | Time from first day of treatment to the first observation of disease progression or death due to any cause, assessed up to 9 years |
| Time to progression | | Time from first day of treatment to the first observation of disease progression or death due to disease, assessed up to 9 years |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate (CR or PR) | Exact 95% confidence intervals will be calculated. | Up to 9 years |
| Time to treatment failure | Estimated using the product-limit method of Kaplan and Meier. | Up to 9 years |
| Duration of response | Estimated using the product-limit method of Kaplan and Meier. | Up to 9 years |
| Incidence by severity and type of toxicity based on the National Cancer Institute (NCI) Common Toxicity Criteria v2.0 and NCI Myalgia Toxicity Grading Scale | | Up to 9 years |
| Association between p53, p21, bcl-2, bax, bcl-2/bax, ERCC-1, and Tdt and tumor response to chemotherapy (CR/PR vs not) | Proportions and Fisher's exact test will be used. Medians, ranges, quartiles and the Wilcoxon two-sample test will be used. | Prior to initiation of chemotherapy |
| Association between p53, p21, bcl-2, bax, bcl-2/bax, ERCC-1, and Tdt and tumor response to chemotherapy (CR/PR vs not) | Proportions and Fisher's exact test will be used. Medians, ranges, quartiles and the Wilcoxon two-sample test will be used. | Day 5 of course 2 |
|
Bryostatin 1, Antineoplastic Agents, Adjuvants, Immunologic, Immunologic Factors, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (bryostatin 1, cisplatin)<br>Patients receive bryostatin 1 IV continuously over 72 hours immediately followed by cisplatin IV over 1 hour. Treatment continues every 3 weeks for a minimum of 2 courses in the absence of disease progression. | Drug: bryostatin 1<br>* Given IV<br>* Other names: Bryostatin;Drug: cisplatin<br>* Given IV<br>* Other names: DDP;Other: laboratory biomarker analysis<br>* Correlative studies<br>|
|
Bryostatin 1 and Cisplatin in Treating Patients With Advanced Recurrent or Residual Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer
Study Overview
=================
Brief Summary
-----------------
Phase II trial to study the effectiveness of combining bryostatin 1 and cisplatin in treating patients who have advanced recurrent or residual ovarian epithelial, fallopian tube, or primary peritoneal cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.
Detailed Description
-----------------
PRIMARY OBJECTIVES: I. To estimate the overall response rate and the complete response rate of patients with platinum-refractory ovarian cancer who are treated with infusional Bryostatin-1 given in combination with intravenous cisplatin. II. To estimate the duration of response in these patients. III. To obtain tissue in order to evaluate the molecular determinants of apoptosis including: p53 status, WAF1/CIP1 gene expression prior to and directly after chemotherapy, bcl-2 gene expression in vivo, bcl-2/bax ratio, p21, and the extent of apoptosis determined by the TdT assay; and the molecular determinants of DNA damage and repair including: expression levels of ERCC1. OUTLINE: This is a multicenter study. Patients receive bryostatin 1 IV continuously over 72 hours immediately followed by cisplatin IV over 1 hour. Treatment continues every 3 weeks for a minimum of 2 courses in the absence of disease progression. Patients are followed for survival. PROJECTED ACCRUAL: A total of 18-32 patients will be accrued for this study within 2 years.
Official Title
-----------------
A Phase II Trial of Bryostatin in Combination With Cisplatin in Patients With Recurrent or Persistent Epithelial Ovarian Cancer
Conditions
-----------------
Fallopian Tube Cancer, Primary Peritoneal Cavity Cancer, Recurrent Ovarian Epithelial Cancer, Stage III Ovarian Epithelial Cancer, Stage IV Ovarian Epithelial Cancer
Intervention / Treatment
-----------------
* Drug: bryostatin 1
* Drug: cisplatin
* Other: laboratory biomarker analysis
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Advanced recurrent or residual ovarian, fallopian tube, or papillary primary peritoneal cancer which has been histologically confirmed Eligible patients include patients with measurable disease who have progressed while on chemotherapeutic treatment, patients with biopsy-proven persistent, clinically-measurable disease with best response as stable at the completion of planned first-line therapy, patients with persistent or recurrent disease with rising CA-125 to levels at least twice normal; the CA-125 increase must be documented by two independent measurements; no patient may have received more than two prior regimens of chemotherapy including first-line treatment Patients must have a Karnofsky performance status of greater than or equal to 50% and an estimated survival of at least three months Measured or calculated clearance >= 60 ml/min AGC >= 1800/mm^3 Plts >= 100,000/mm^3 Bilirubin =< 1.5 mg/dl SGOT less than 2 x upper limit of normal Previous radiotherapy or chemotherapy must have been completed at least three weeks before treatment under this protocol Patients must have the ability to give voluntary informed consent and to comply with the treatment and required tests Because Bryostatin is of unknown teratogenic potential, women of childbearing potential must have a negative pregnancy test and must take adequate precautions to prevent pregnancy during treatment Patients with any non-malignant intercurrent illness (e.g. cardiovascular, pulmonary, or central nervous system disease) which is either poorly controlled with currently available treatment, or is of such severity that the investigators deem it unwise to enter the patient on protocol shall be ineligible Patients currently being treated for severe infection or who are recovering from major surgery are ineligible until recovery is deemed complete by the investigator The extent of all evaluable and nonevaluable disease must be documented; pretreatment radiographic examinations should be done no earlier than 4 weeks (28 days) prior to the first course of chemotherapy; pre-treatment chemistries and CA-125 levels should be done no earlier than two weeks (14 days) prior to initiation of chemotherapy; (in calculating days of tests and measurements, the day a test or measurement is done is considered day 0; therefore, if a test is done on Monday, the Monday four weeks later would be considered day 28; this allows for efficient patient scheduling without exceeding the guidelines)
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (bryostatin 1, cisplatin)<br>Patients receive bryostatin 1 IV continuously over 72 hours immediately followed by cisplatin IV over 1 hour. Treatment continues every 3 weeks for a minimum of 2 courses in the absence of disease progression. | Drug: bryostatin 1<br>* Given IV<br>* Other names: Bryostatin;Drug: cisplatin<br>* Given IV<br>* Other names: DDP;Other: laboratory biomarker analysis<br>* Correlative studies<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | | Time from first day of treatment to time of death due to any cause, assessed up to 9 years |
| Progression-free survival | | Time from first day of treatment to the first observation of disease progression or death due to any cause, assessed up to 9 years |
| Time to progression | | Time from first day of treatment to the first observation of disease progression or death due to disease, assessed up to 9 years |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate (CR or PR) | Exact 95% confidence intervals will be calculated. | Up to 9 years |
| Time to treatment failure | Estimated using the product-limit method of Kaplan and Meier. | Up to 9 years |
| Duration of response | Estimated using the product-limit method of Kaplan and Meier. | Up to 9 years |
| Incidence by severity and type of toxicity based on the National Cancer Institute (NCI) Common Toxicity Criteria v2.0 and NCI Myalgia Toxicity Grading Scale | | Up to 9 years |
| Association between p53, p21, bcl-2, bax, bcl-2/bax, ERCC-1, and Tdt and tumor response to chemotherapy (CR/PR vs not) | Proportions and Fisher's exact test will be used. Medians, ranges, quartiles and the Wilcoxon two-sample test will be used. | Prior to initiation of chemotherapy |
| Association between p53, p21, bcl-2, bax, bcl-2/bax, ERCC-1, and Tdt and tumor response to chemotherapy (CR/PR vs not) | Proportions and Fisher's exact test will be used. Medians, ranges, quartiles and the Wilcoxon two-sample test will be used. | Day 5 of course 2 |
|
|
NCT04846166
|
I-Smads in Periodontitis
|
Recently, it has been stated that Smads play an active role in all conditions where transforming growth factor-beta (TGF-β) is involved, including periodontal inflammation. This study aimed to examine the levels of TGF-β and inhibitor Smads in saliva and gingival crevicular fluid (GCF) in patients with Stage 3 Grade B periodontitis before and after non-surgical periodontal treatment. Twenty (20) stage 3 grade B periodontitis and 20 periodontally healthy individuals were included in the study. Clinical periodontal measurements were recorded; periodontitis patients received non-surgical periodontal treatment, and GCF and saliva samples were obtained at baseline and one month after treatment. TGF-β, Smad6, and Smad7 were determined by ELISA.
|
Role of Inhibitor SMADs in Stage 3 Grade B Periodontitis Before and After Periodontal Treatment
|
Treatment Adherence, Periodontitis
|
* Diagnostic Test: Periodontally healthy group
* Diagnostic Test: Periodontitis
|
Inclusion Criteria:~Have at least 20 natural teeth, excluding third molars.~Periodontitis patients had at least two non-adjacent sites per quadrant with probing depth (PD) ≥ 5 mm and clinical attachment level (CAL) ≥ 5 mm with gingival inflammation, and alveolar bone loss affecting >30% of the teeth, as detected on clinical and radiographical examinations.~Periodontally healthy control group had no sign of gingival inflammation, no PD > 3mm and no evidence of attachment or bone loss~Exclusion Criteria:~History of systemic disease.~Regular use of any drugs which can effect the immune system or inflammatory response in the 6 months preceding the start of the study.~Periodontal treatment during last 6 months that could affect periodontal status.~Smoking.~History of radiotherapy or chemotherapy.~Current pregnancy, lactation or menopause.
|
25 Years
|
55 Years
|
All
|
Accepts Healthy Volunteers
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TGF-β, Smad6, and Smad7 levels | the levels of TGF-β, Smad6, and Smad7 in gingival crevicular fluid (GCF) and saliva | baseline |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TGF-β, Smad6, and Smad7 levels | the levels of TGF-β, Smad6, and Smad7 in gingival crevicular fluid (GCF) and saliva before and after non-surgical periodontal treatment. | baseline and 1st month after treatment |
|
Smad, Periodontitis, Gingival crevicular fluid, Saliva
|
Periodontitis, Periodontal Diseases, Mouth Diseases, Stomatognathic Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Control<br> | Diagnostic Test: Periodontally healthy group<br>* probing pocket depth (PPD)≤ 3 mm (presence of normal gingival sulcus), bleeding on probing (BOP) < 10%, clinical absence of periodontal inflammation, radiological bone loss, and any prior periodontal disease, additionally presence of anatomically intact periodontium<br>|
| Periodontitis<br> | Diagnostic Test: Periodontitis<br>* : interdental clinical attachment level (CAL) ≥ 5 mm and PPD ≥ 6 mm on at least two non-adjacent teeth, bone loss involving the middle or apical third of the root radiographically, moderate ridge defect and ≥30% of teeth<br>|
|
I-Smads in Periodontitis
Study Overview
=================
Brief Summary
-----------------
Recently, it has been stated that Smads play an active role in all conditions where transforming growth factor-beta (TGF-β) is involved, including periodontal inflammation. This study aimed to examine the levels of TGF-β and inhibitor Smads in saliva and gingival crevicular fluid (GCF) in patients with Stage 3 Grade B periodontitis before and after non-surgical periodontal treatment. Twenty (20) stage 3 grade B periodontitis and 20 periodontally healthy individuals were included in the study. Clinical periodontal measurements were recorded; periodontitis patients received non-surgical periodontal treatment, and GCF and saliva samples were obtained at baseline and one month after treatment. TGF-β, Smad6, and Smad7 were determined by ELISA.
Official Title
-----------------
Role of Inhibitor SMADs in Stage 3 Grade B Periodontitis Before and After Periodontal Treatment
Conditions
-----------------
Treatment Adherence, Periodontitis
Intervention / Treatment
-----------------
* Diagnostic Test: Periodontally healthy group
* Diagnostic Test: Periodontitis
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Have at least 20 natural teeth, excluding third molars. Periodontitis patients had at least two non-adjacent sites per quadrant with probing depth (PD) ≥ 5 mm and clinical attachment level (CAL) ≥ 5 mm with gingival inflammation, and alveolar bone loss affecting >30% of the teeth, as detected on clinical and radiographical examinations. Periodontally healthy control group had no sign of gingival inflammation, no PD > 3mm and no evidence of attachment or bone loss Exclusion Criteria: History of systemic disease. Regular use of any drugs which can effect the immune system or inflammatory response in the 6 months preceding the start of the study. Periodontal treatment during last 6 months that could affect periodontal status. Smoking. History of radiotherapy or chemotherapy. Current pregnancy, lactation or menopause.
Ages Eligible for Study
-----------------
Minimum Age: 25 Years
Maximum Age: 55 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Control<br> | Diagnostic Test: Periodontally healthy group<br>* probing pocket depth (PPD)≤ 3 mm (presence of normal gingival sulcus), bleeding on probing (BOP) < 10%, clinical absence of periodontal inflammation, radiological bone loss, and any prior periodontal disease, additionally presence of anatomically intact periodontium<br>|
| Periodontitis<br> | Diagnostic Test: Periodontitis<br>* : interdental clinical attachment level (CAL) ≥ 5 mm and PPD ≥ 6 mm on at least two non-adjacent teeth, bone loss involving the middle or apical third of the root radiographically, moderate ridge defect and ≥30% of teeth<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TGF-β, Smad6, and Smad7 levels | the levels of TGF-β, Smad6, and Smad7 in gingival crevicular fluid (GCF) and saliva | baseline |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TGF-β, Smad6, and Smad7 levels | the levels of TGF-β, Smad6, and Smad7 in gingival crevicular fluid (GCF) and saliva before and after non-surgical periodontal treatment. | baseline and 1st month after treatment |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Smad, Periodontitis, Gingival crevicular fluid, Saliva
|
||
NCT00691535
|
Genetics of Symptomatology and Treatment Response in Psychotic Major Depression
|
We hope to learn more about the biology of psychiatric illness with the hope of improving the diagnosis and treatment of such psychiatric conditions as major depression.
|
From the blood sample you donate, the researchers will obtain DNA. This DNA will be used to search for DNA markers related to the underlying biology of psychiatric illness and how this might explain the symptoms of these disorders. Research using DNA is an important way to try to understand human disease and/or the role genes play in disease. In effect, part of your blood sample will be used to attempt to understand how genetic factors contribute to the symptoms of such psychiatric conditions as major depression.
|
Association of BDNF, COMT, MDRI, CRH, CRF, and GC Receptor Genetic Polymorphisms With Symptomatology and Treatment Response in Psychotic Major Depression
|
Psychotic Disorders, Depressive Disorder, Depressive Disorder, Major
|
Inclusion Criteria:~You are currently experiencing symptoms that are consistent with an episode of major depression without symptoms of psychosis (such as hallucinations, delusions or disorder of thought process), or~You are currently experiencing symptoms that are consistent with an episode of major depression with symptoms of psychosis (such as hallucinations, delusions or disorder of thought process), or~You have been diagnosed with either schizophrenia or schizoaffective disorder, or~You are a volunteer without a history of psychiatric illness (a healthy control subject).
| null | null |
All
|
Accepts Healthy Volunteers
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
|
Depression, Depressive Disorder, Depressive Disorder, Major, Mental Disorders, Psychotic Disorders, Behavioral Symptoms, Mood Disorders, Schizophrenia Spectrum and Other Psychotic Disorders
|
Genetics of Symptomatology and Treatment Response in Psychotic Major Depression
Study Overview
=================
Brief Summary
-----------------
We hope to learn more about the biology of psychiatric illness with the hope of improving the diagnosis and treatment of such psychiatric conditions as major depression.
Detailed Description
-----------------
From the blood sample you donate, the researchers will obtain DNA. This DNA will be used to search for DNA markers related to the underlying biology of psychiatric illness and how this might explain the symptoms of these disorders. Research using DNA is an important way to try to understand human disease and/or the role genes play in disease. In effect, part of your blood sample will be used to attempt to understand how genetic factors contribute to the symptoms of such psychiatric conditions as major depression.
Official Title
-----------------
Association of BDNF, COMT, MDRI, CRH, CRF, and GC Receptor Genetic Polymorphisms With Symptomatology and Treatment Response in Psychotic Major Depression
Conditions
-----------------
Psychotic Disorders, Depressive Disorder, Depressive Disorder, Major
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: You are currently experiencing symptoms that are consistent with an episode of major depression without symptoms of psychosis (such as hallucinations, delusions or disorder of thought process), or You are currently experiencing symptoms that are consistent with an episode of major depression with symptoms of psychosis (such as hallucinations, delusions or disorder of thought process), or You have been diagnosed with either schizophrenia or schizoaffective disorder, or You are a volunteer without a history of psychiatric illness (a healthy control subject).
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
|
|||||
NCT02405169
|
4 vs 6 Implants in Totally Edentulous Patient in Maxilla With Ti. Cad-cam Framework
|
The primary objective of the present study is to evaluate the marginal bone level changes occurring in total edentulous patients treated with six or four implants.~Secondary objective~overall survival rate~soft tissue status by assessment of bleeding on probing (BoP) and probing pocket depth (PPD) at baseline and after 1,3,5 years~prosthetic survival rates including screw or abutment loosening, framework or veneer fractures
|
METHODS/PROCEDURES A randomized controlled multi-center clinical study is designed to determine whether a difference exists between the outcome of treatment when Astra tech implants are placed according to a six or a four implants protocol. The investigation will be performed in four centers: three in Italy affiliated to Institute Franci and one affiliated to the Department of Prosthodontics, Faculty of Odontology, Malmö University. In each center the clinician and the examiner will be the same person. The study protocol will be approved by the Regional Human Review Board of Padova General Hospital.~An investigators' meeting will be arranged prior to the starting with the patients' recruitment. Following a screening examination, subjects who will meet the inclusion criteria, will sign the Informed Consent and will be enrolled in the study. The period of patient enrollment will begin on January 1 2013 and ends December 31 2013.~The patients will be randomized with a method based on the use of sealed opaque envelopes. The cases will be assigned to two different treatment groups:~Group A- four implants (Test) Group B- six implants (Control)~Pre-treatment Patient data, medical history, clinical and radiographic examination will be recorded for each patient. Clinical photographs will be taken in frontal, occlusal and lateral projections.~Periodontal, endodontic and open caries lesions will be treated prior to implant installation. All patients will receive careful oral hygiene instructions and training in self-performed~plaque control measure. CT scan computed exams will be carried out. Plaster models and diagnostic wax-up will be carried out.~First Surgical Phase (Implant Installation) The patient will receive antibiotic prophylaxis (Amoxicillin 1gr) one hour prior to surgery and after the completion of implant installation until suture removal with 1gr three times a day. (If the patient is allergic to amoxicillin the examiner prescribes antibiotics at his own discretion at the same posology).~The surgical treatment will be performed under local anesthesia. In case of remaining teeth, they will be extracted with conventional technique before implants' placement. (13-14) Implants will be placed according to the guidelines described in the Astra Tech® manual Surgical procedures, using a two-stage protocol.~Implant spinning during the positioning of the cover screw will be registered as positive, if present, or negative.~The operation will be finalized by a careful adaption of the flaps by means of an accurate suture in order to obtain a full periosteal coverage.~Intraoral clinical photographs before, during and after surgery will be taken.~Post-operative care The patients will be instructed to rinse with chlorhexidine 0.12% mouthrinse and will be told to rinse with the antiseptic solution three times a day for 2 weeks. The patients will be advised to take NSAIDs for pain relief at their own discretion.~Liquid and semisolid food will be prescribed for the first post-operative week, after which the sutures will be removed.~Two weeks after the operation the denture will be properly relined until the second stage surgery.~Patients will be controlled at third and sixth weeks.~Second surgical phase and Prosthetic procedures After eight weeks (+ 2) of healing in both groups (A and B) Uni Abutment 45° connection procedure will be performed. Impression with a customized spoon and Impregum material will be taken and the prosthetic procedure will be performed according to the Atlantis-Isus recommendations.~After 6 weeks (+ 2) from Uni Abutment connection the definitive full-arch fixed dental prostheses screw retained will be applied. The prosthesis will be made to accomplish the normal hygienic procedures. All prosthetic procedures will be made in accordance to the Astra Tech procedures & products manuals.~The length of bridge cantilevers will be duly calculated to minimize implant overloading according to the Atlantis-Isus recommendations (15)~Post-prosthetic measurements Clinical measurements Clinical examinations will be performed immediately following the installation of the definitive prosthesis (Baseline-Loading) and after 1, 3, and 5 years. In particular, plaque and soft-tissue inflammation will be registered. Clinical photographs will be taken at each interval point.~Plaque: the presence of plaque will be scored at each implant site as well as at level of the remaining teeth on four surfaces (buccal, lingual/palatal, mesial, distal). The mean percentage of plaque harboring surfaces will be calculated using the case as the unit.~Soft-tissue inflammation: the presence of soft-tissue inflammation (bleeding on probing) will be assessed on buccal, lingual/palatal, mesial, distal aspects of each implant. The mean percentage of inflamed sites will be calculated using the case as the unit.~Radiographic measurements Peri-apical radiographs will be taken at prosthesis insertion (Baseline) and after 1, 3, and 5 years.~The radiographs will be taken with an X-ray apparatus supplied with a long cone by the examiner each visiting time. Rinn centrators will be used to ensure reproducibility in the measurement of marginal bone level change.~The radiographic images will be analysed at the Department of Radiology of Sahlgrenska Academy, Gothenburg University by experienced radiologists who will be otherwise not involved in the study.
|
Four Versus Six Endosseous Implants to be Used in the Rehabilitation of Totally Edentulous Patient in the Maxilla With Titanium Milled Framework
|
Edentulous Maxilla
|
* Device: 4 vs 6 implant treatment in the maxilla
|
Inclusion Criteria:~Inclusion criteria:~age > 18 years;~edentulous maxilla or having hopeless remaining teeth that are intended to be extracted;~willingness to comply with all study requirements and to sign the IC;~have sufficient amount of bone (8mm or more) in the recipient site to allow implant placement without bone augmentation procedures.~Exclusion Criteria:~bone defects associated with severe knife-edge ridges;~bone defects resulting from tumor resection;~tobacco abuse (> 10 cigarettes/day);~severe kidney and liver disease;~history of radiotherapy in the head and neck region;~chemotherapy for treatment of malignant tumors at the time of the surgical procedure;~uncontrolled diabetes;~active periodontal disease involving the residual opposite dentition;~mucosal disease, such as lichen planus, in the areas to be treated;~poor oral hygiene;~non-compliant patients;~situations judged inconvenient(by the investigator) for the surgical treatment.
|
18 Years
|
90 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Marginal bone resorption in millimeter from the the implant to the bone crest. | | 1 year |
| Marginal bone resorption in millimeter from the the implant to the bone crest. | | 3 year |
| Marginal bone resorption in millimeter from the the implant to the bone crest. | | 5 year |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fracture of the prosthetic components | | 1 year |
| Fracture of the prosthetic components | | 3 year |
| Fracture of the prosthetic components | | 5 year |
|
Implantology, oral surgery, bone level changes, marginal bone level
|
Mouth, Edentulous, Mouth Diseases, Stomatognathic Diseases, Tooth Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test -4 implants-<br>Evaluate marginal bone level (MBL) changes at implants that are placed in total edentulous patient when they are treated with four with titanium Cad/Cam framework. | Device: 4 vs 6 implant treatment in the maxilla<br> <br> * Other names: Astratech TX implant , Densply Implant (company name);|
| Active Comparator: Control -6 implants-<br>Evaluate marginal bone level (MBL) changes at implants that are placed in total edentulous patient when they are treated with six with titanium Cad/Cam framework | Device: 4 vs 6 implant treatment in the maxilla<br> <br> * Other names: Astratech TX implant , Densply Implant (company name);|
|
4 vs 6 Implants in Totally Edentulous Patient in Maxilla With Ti. Cad-cam Framework
Study Overview
=================
Brief Summary
-----------------
The primary objective of the present study is to evaluate the marginal bone level changes occurring in total edentulous patients treated with six or four implants. Secondary objective overall survival rate soft tissue status by assessment of bleeding on probing (BoP) and probing pocket depth (PPD) at baseline and after 1,3,5 years prosthetic survival rates including screw or abutment loosening, framework or veneer fractures
Detailed Description
-----------------
METHODS/PROCEDURES A randomized controlled multi-center clinical study is designed to determine whether a difference exists between the outcome of treatment when Astra tech implants are placed according to a six or a four implants protocol. The investigation will be performed in four centers: three in Italy affiliated to Institute Franci and one affiliated to the Department of Prosthodontics, Faculty of Odontology, Malmö University. In each center the clinician and the examiner will be the same person. The study protocol will be approved by the Regional Human Review Board of Padova General Hospital. An investigators' meeting will be arranged prior to the starting with the patients' recruitment. Following a screening examination, subjects who will meet the inclusion criteria, will sign the Informed Consent and will be enrolled in the study. The period of patient enrollment will begin on January 1 2013 and ends December 31 2013. The patients will be randomized with a method based on the use of sealed opaque envelopes. The cases will be assigned to two different treatment groups: Group A- four implants (Test) Group B- six implants (Control) Pre-treatment Patient data, medical history, clinical and radiographic examination will be recorded for each patient. Clinical photographs will be taken in frontal, occlusal and lateral projections. Periodontal, endodontic and open caries lesions will be treated prior to implant installation. All patients will receive careful oral hygiene instructions and training in self-performed plaque control measure. CT scan computed exams will be carried out. Plaster models and diagnostic wax-up will be carried out. First Surgical Phase (Implant Installation) The patient will receive antibiotic prophylaxis (Amoxicillin 1gr) one hour prior to surgery and after the completion of implant installation until suture removal with 1gr three times a day. (If the patient is allergic to amoxicillin the examiner prescribes antibiotics at his own discretion at the same posology). The surgical treatment will be performed under local anesthesia. In case of remaining teeth, they will be extracted with conventional technique before implants' placement. (13-14) Implants will be placed according to the guidelines described in the Astra Tech® manual Surgical procedures, using a two-stage protocol. Implant spinning during the positioning of the cover screw will be registered as positive, if present, or negative. The operation will be finalized by a careful adaption of the flaps by means of an accurate suture in order to obtain a full periosteal coverage. Intraoral clinical photographs before, during and after surgery will be taken. Post-operative care The patients will be instructed to rinse with chlorhexidine 0.12% mouthrinse and will be told to rinse with the antiseptic solution three times a day for 2 weeks. The patients will be advised to take NSAIDs for pain relief at their own discretion. Liquid and semisolid food will be prescribed for the first post-operative week, after which the sutures will be removed. Two weeks after the operation the denture will be properly relined until the second stage surgery. Patients will be controlled at third and sixth weeks. Second surgical phase and Prosthetic procedures After eight weeks (+ 2) of healing in both groups (A and B) Uni Abutment 45° connection procedure will be performed. Impression with a customized spoon and Impregum material will be taken and the prosthetic procedure will be performed according to the Atlantis-Isus recommendations. After 6 weeks (+ 2) from Uni Abutment connection the definitive full-arch fixed dental prostheses screw retained will be applied. The prosthesis will be made to accomplish the normal hygienic procedures. All prosthetic procedures will be made in accordance to the Astra Tech procedures & products manuals. The length of bridge cantilevers will be duly calculated to minimize implant overloading according to the Atlantis-Isus recommendations (15) Post-prosthetic measurements Clinical measurements Clinical examinations will be performed immediately following the installation of the definitive prosthesis (Baseline-Loading) and after 1, 3, and 5 years. In particular, plaque and soft-tissue inflammation will be registered. Clinical photographs will be taken at each interval point. Plaque: the presence of plaque will be scored at each implant site as well as at level of the remaining teeth on four surfaces (buccal, lingual/palatal, mesial, distal). The mean percentage of plaque harboring surfaces will be calculated using the case as the unit. Soft-tissue inflammation: the presence of soft-tissue inflammation (bleeding on probing) will be assessed on buccal, lingual/palatal, mesial, distal aspects of each implant. The mean percentage of inflamed sites will be calculated using the case as the unit. Radiographic measurements Peri-apical radiographs will be taken at prosthesis insertion (Baseline) and after 1, 3, and 5 years. The radiographs will be taken with an X-ray apparatus supplied with a long cone by the examiner each visiting time. Rinn centrators will be used to ensure reproducibility in the measurement of marginal bone level change. The radiographic images will be analysed at the Department of Radiology of Sahlgrenska Academy, Gothenburg University by experienced radiologists who will be otherwise not involved in the study.
Official Title
-----------------
Four Versus Six Endosseous Implants to be Used in the Rehabilitation of Totally Edentulous Patient in the Maxilla With Titanium Milled Framework
Conditions
-----------------
Edentulous Maxilla
Intervention / Treatment
-----------------
* Device: 4 vs 6 implant treatment in the maxilla
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Inclusion criteria: age > 18 years; edentulous maxilla or having hopeless remaining teeth that are intended to be extracted; willingness to comply with all study requirements and to sign the IC; have sufficient amount of bone (8mm or more) in the recipient site to allow implant placement without bone augmentation procedures. Exclusion Criteria: bone defects associated with severe knife-edge ridges; bone defects resulting from tumor resection; tobacco abuse (> 10 cigarettes/day); severe kidney and liver disease; history of radiotherapy in the head and neck region; chemotherapy for treatment of malignant tumors at the time of the surgical procedure; uncontrolled diabetes; active periodontal disease involving the residual opposite dentition; mucosal disease, such as lichen planus, in the areas to be treated; poor oral hygiene; non-compliant patients; situations judged inconvenient(by the investigator) for the surgical treatment.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 90 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test -4 implants-<br>Evaluate marginal bone level (MBL) changes at implants that are placed in total edentulous patient when they are treated with four with titanium Cad/Cam framework. | Device: 4 vs 6 implant treatment in the maxilla<br> <br> * Other names: Astratech TX implant , Densply Implant (company name);|
| Active Comparator: Control -6 implants-<br>Evaluate marginal bone level (MBL) changes at implants that are placed in total edentulous patient when they are treated with six with titanium Cad/Cam framework | Device: 4 vs 6 implant treatment in the maxilla<br> <br> * Other names: Astratech TX implant , Densply Implant (company name);|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Marginal bone resorption in millimeter from the the implant to the bone crest. | | 1 year |
| Marginal bone resorption in millimeter from the the implant to the bone crest. | | 3 year |
| Marginal bone resorption in millimeter from the the implant to the bone crest. | | 5 year |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fracture of the prosthetic components | | 1 year |
| Fracture of the prosthetic components | | 3 year |
| Fracture of the prosthetic components | | 5 year |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Implantology, oral surgery, bone level changes, marginal bone level
|
NCT05319574
|
SBRT Followed by Neoadjuvant Immunochemotherapy in Resectable Stage IB to III Non-small Cell Lung Cancer
|
The purpose of this study is to find out the effectiveness stereotactic body radiation therapy (SBRT) followed by two cycles of Tislelizumab (PD-1 inhibitor) with chemotherapy as treatment for operable stage IB (tumors > 4cm) to III non-small cell lung cancer (NSCLC) prior to surgery.
|
Preoperative Stereotactic Body Radiotherapy and Platinum-based Doublet Chemotherapy Plus Tislelizumab (Immunotherapy) for Operable Stage IB to III EGFR Wild-type Non-small Cell Lung Cancer
|
Carcinoma, Non-Small-Cell Lung
|
* Radiation: SBRT
* Drug: Tislelizumab
|
Inclusion Criteria:~Patient has histologically or cytologically proven clinical stages I (tumors ≥ 4 cm), II, and IIIA NSCLC and is considered eligible for surgical resection with curative intent. Besides, T3-4N2 stage III disease deemed potentially resectable by MDT group is also allowed.~Measureable disease, as defined by RECIST v1.1.~Written informed consent and HIPAA obtained from the subject prior to performing any protocol-related procedures.~EGFR mutational status should be tested in all non-squamous carcinoma, and only patients with non-EGFR-TKI sensitizing mutation (19del or L858R) are allowed. For squamous cell carcinoma, EGFR mutational test is not required.~Age > 18 years at time of study entry~Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.~Adequate normal organ and marrow function as defined below:~Haemoglobin ≥ 9.0 g/dL~Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (> 1500 per mm3)~Platelet count ≥ 100 x 109/L (>100,000 per mm3)~Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.~AST (SGOT)/ALT (SGPT), and alkaline phosphatase ≤ 2.5 x institutional upper limit of normal (ULN).~Serum creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:~Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:~Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).~Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).~Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.~No prior therapy for their lung cancer.~Exclusion Criteria:~Participation in another clinical study with an investigational product during the last 3 weeks.~History of another primary malignancy except for:~Malignancy treated with curative intent and with no known active disease ≥3 years before the first dose of study drug and of low potential risk for recurrence.~Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.~Adequately treated carcinoma in situ without evidence of disease eg, cervical cancer in situ, in-situ urinary bladder cancer , treated localized prostate cancer and ductal carcinoma-in situ.~Indolent hematological malignancies~Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab, with the exceptions of intranasal,inhaled, topical steroids, or local steroid injections (e.g., intra articular injection), corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid, and steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).~Any unresolved toxicity (CTCAE grade 2) from therapy for a prior malignancy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.~Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.~Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripherally neuropathy).~Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1.~Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). No active diverticulitis within the previous 3 months. The following are exceptions to this criterion:~Patients with vitiligo or alopecia~Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement~Any chronic skin condition that does not require systemic therapy~Patients without active disease in the last 5 years may be included but only after consultation with the study physician~Patients with celiac disease controlled by diet alone~Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).~History of active primary immunodeficiency.~History of allogeneic organ transplant.~History of hypersensitivity to tislelizumab or any excipient.~Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.~Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.~History of leptomeningeal carcinomatosis.~Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results~Subjects with uncontrolled seizures.~History of interstitial lung disease, idiopathic pulmonary fibrosis, pneumonitis (including drug induced), or evidence of active pneumonitis on screening chest CT scan.
|
18 Years
|
75 Years
|
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Pathological Response (MPR) | MPR is defined as ≤10% residual viable tumor in the resected specimen | From date of enrollment until one month after resection |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic Complete response (PCR) | PCR is defined as no residual viable tumor in the resected specimen | From date of enrollment until one month after resection |
| Resected rate | Resected rate is defined as the percentage of patients that undergo surgical resection after neoadjuvant treatment | From date of enrollment to an average of 18 weeks after the first dose |
| Disease-free survival | Disease recurrence or death from any cause assessed using history, physical examination and CT scanning, histologically or cytologically confirmed whenever possible | From date of SBRT start date until the date of first documented progression or date of death from any cause, whichever came first, assessed every 6 months for 2 years , then yearly thereafter till year 5 |
|
Non small cell lung cancer, Neoadjuvant, Immunotherapy, SBRT
|
Tislelizumab, Antineoplastic Agents, Immunological, Antineoplastic Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neoadjuvant SBRT plus immunochemotherapy<br>Stereotactic body radiation therapy (8Gy*3d) followed by Tislelizumab (200mg) with platinum-based doublet chemotherapy administered pre-operatively every 3 weeks for 2 cycles before surgical resection | Radiation: SBRT<br>* Stereotactic body radiation therapy delivered with a fixed dose (8Gy) in 3 daily fractions 1-7 days before the first cycle of immunochemotherapy<br>* Other names: stereotactic body radiation therapy;Drug: Tislelizumab<br>* 200mg q3w for two cycles administrated concurrently with chemotherapy<br>|
|
SBRT Followed by Neoadjuvant Immunochemotherapy in Resectable Stage IB to III Non-small Cell Lung Cancer
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to find out the effectiveness stereotactic body radiation therapy (SBRT) followed by two cycles of Tislelizumab (PD-1 inhibitor) with chemotherapy as treatment for operable stage IB (tumors > 4cm) to III non-small cell lung cancer (NSCLC) prior to surgery.
Official Title
-----------------
Preoperative Stereotactic Body Radiotherapy and Platinum-based Doublet Chemotherapy Plus Tislelizumab (Immunotherapy) for Operable Stage IB to III EGFR Wild-type Non-small Cell Lung Cancer
Conditions
-----------------
Carcinoma, Non-Small-Cell Lung
Intervention / Treatment
-----------------
* Radiation: SBRT
* Drug: Tislelizumab
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient has histologically or cytologically proven clinical stages I (tumors ≥ 4 cm), II, and IIIA NSCLC and is considered eligible for surgical resection with curative intent. Besides, T3-4N2 stage III disease deemed potentially resectable by MDT group is also allowed. Measureable disease, as defined by RECIST v1.1. Written informed consent and HIPAA obtained from the subject prior to performing any protocol-related procedures. EGFR mutational status should be tested in all non-squamous carcinoma, and only patients with non-EGFR-TKI sensitizing mutation (19del or L858R) are allowed. For squamous cell carcinoma, EGFR mutational test is not required. Age > 18 years at time of study entry Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Adequate normal organ and marrow function as defined below: Haemoglobin ≥ 9.0 g/dL Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (> 1500 per mm3) Platelet count ≥ 100 x 109/L (>100,000 per mm3) Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician. AST (SGOT)/ALT (SGPT), and alkaline phosphatase ≤ 2.5 x institutional upper limit of normal (ULN). Serum creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance: Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy). Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy). Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. No prior therapy for their lung cancer. Exclusion Criteria: Participation in another clinical study with an investigational product during the last 3 weeks. History of another primary malignancy except for: Malignancy treated with curative intent and with no known active disease ≥3 years before the first dose of study drug and of low potential risk for recurrence. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. Adequately treated carcinoma in situ without evidence of disease eg, cervical cancer in situ, in-situ urinary bladder cancer , treated localized prostate cancer and ductal carcinoma-in situ. Indolent hematological malignancies Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab, with the exceptions of intranasal,inhaled, topical steroids, or local steroid injections (e.g., intra articular injection), corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid, and steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication). Any unresolved toxicity (CTCAE grade 2) from therapy for a prior malignancy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria. Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripherally neuropathy). Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). No active diverticulitis within the previous 3 months. The following are exceptions to this criterion: Patients with vitiligo or alopecia Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement Any chronic skin condition that does not require systemic therapy Patients without active disease in the last 5 years may be included but only after consultation with the study physician Patients with celiac disease controlled by diet alone Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis). History of active primary immunodeficiency. History of allogeneic organ transplant. History of hypersensitivity to tislelizumab or any excipient. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. History of leptomeningeal carcinomatosis. Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results Subjects with uncontrolled seizures. History of interstitial lung disease, idiopathic pulmonary fibrosis, pneumonitis (including drug induced), or evidence of active pneumonitis on screening chest CT scan.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neoadjuvant SBRT plus immunochemotherapy<br>Stereotactic body radiation therapy (8Gy*3d) followed by Tislelizumab (200mg) with platinum-based doublet chemotherapy administered pre-operatively every 3 weeks for 2 cycles before surgical resection | Radiation: SBRT<br>* Stereotactic body radiation therapy delivered with a fixed dose (8Gy) in 3 daily fractions 1-7 days before the first cycle of immunochemotherapy<br>* Other names: stereotactic body radiation therapy;Drug: Tislelizumab<br>* 200mg q3w for two cycles administrated concurrently with chemotherapy<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Pathological Response (MPR) | MPR is defined as ≤10% residual viable tumor in the resected specimen | From date of enrollment until one month after resection |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic Complete response (PCR) | PCR is defined as no residual viable tumor in the resected specimen | From date of enrollment until one month after resection |
| Resected rate | Resected rate is defined as the percentage of patients that undergo surgical resection after neoadjuvant treatment | From date of enrollment to an average of 18 weeks after the first dose |
| Disease-free survival | Disease recurrence or death from any cause assessed using history, physical examination and CT scanning, histologically or cytologically confirmed whenever possible | From date of SBRT start date until the date of first documented progression or date of death from any cause, whichever came first, assessed every 6 months for 2 years , then yearly thereafter till year 5 |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Non small cell lung cancer, Neoadjuvant, Immunotherapy, SBRT
|
|
NCT02025075
|
Hemodynamic and Respiratory Variations During Laparoscopic Surgery With and Without Deep Neuromuscular Blockade.
|
The goal of this study is to investigate the effect of depth of neuromuscular block (NMB) on global and regional (dependent versus nondependent) respiratory mechanics during laparoscopic surgery. Furthermore, we will investigate if the level of NMB influences intraoperative hemodynamic and cerebral oxygenation.
|
A Prospective, Double-blind, Randomized, Crossover Design Study to Compare the Hemodynamic and Respiratory Variations During Laparoscopic Surgery in Patients With and Without Deep Neuromuscular Blockade.
|
Intraoperative Complications, Postoperative Complications, Laparoscopy, Surgical Complications From General Anesthesia, Ventilator-Induced Lung Injury
|
* Drug: Rocuronium
|
Inclusion Criteria:~Age 18 years or older~Elective patients scheduled to undergo laparoscopic surgery with expected duration > 2h~Physical status ASA I - III~Exclusion Criteria:~Pregnancy~Severe cardiac disease (NYHA class III or IV, acute coronary syndrome, or persistent ventricular tachyarrhythmia)~Previous lung surgery~History of severe chronic obstructive pulmonary disease~Gastro-esophageal pathology (including but not limited to recent gastric or esophageal surgery including bypass/banding, history of esophageal varices, known anatomical gastric or esophageal defects such as strictures, hernias or fistulas)~Mechanical ventilation within the last 30 days~Neuromuscular disease~Consented for another interventional study or refusal to participate in the present study~Hypersensitivity (e.g., anaphylaxis) to rocuronium bromide or other neuromuscular blocking agents
|
18 Years
| null |
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Regional Change in Air Content (Delta Z, %) | We will measure continuous respiratory flows and pressures in the intraoperative period to assess continuously the compliance and resistance of the respiratory system (T1 to T5). In addition, we will use an esophageal balloon to assess esophageal pressures and partition the global mechanical properties of the respiratory system, into their lung and chest wall components (T1 to T5). Regional lung aeration will be assessed for quantification of intraoperative lung recruitment using Electrical Impedance Tomography (EIT) (T0 to T6). Percent change was calculated using electrical impedance measurements obtained at time T0 as reference. | BL; During pneumoperitoneum; Stage w/2 depths neuromuscular blockade targeted - TOF1 and Deep: 1-2 twitches in post-tetanic count (50-Hz tetanus followed by three-second pause and 15 1-Hz stimuli); and immediately after release of pneumoperitoneum |
| Ejection Fraction (%) | To assess cardiac performance, transthoracic echocardiography will be used. Ejection fraction was measured as fractional shortening (FS). FS is the fraction of any diastolic dimension that is lost in systole. FS = 100*(LVEDD - LVESD) / LVEDD, LVEDD = LV end-diastolic dimension (mm); LVESD = LV end-systolic dimension (mm). | BL; During pneumoperitoneum; Stage w/2 depths neuromuscular blockade targeted - TOF1 and Deep: 1-2 twitches in post-tetanic count (50-Hz tetanus followed by three-second pause and 15 1-Hz stimuli); and immediately after release of pneumoperitoneum |
| Cerebral Oximetry (%) | Regional cerebral oxygenation will be assessed continuously during the intraoperative period using NIRS technology. | BL; During pneumoperitoneum; Stage w/2 depths neuromuscular blockade targeted - TOF1 and Deep: 1-2 twitches in post-tetanic count (50-Hz tetanus followed by three-second pause and 15 1-Hz stimuli); and immediately after release of pneumoperitoneum |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative Pain | The patient will be inquired about pain with a visual analogue scale (VAS). Pain will be evaluated as incisional pain using VAS (0 = no pain; 100 = worst possible pain). | Postoperative Day 1 |
|
Tomography, Oximetry, Echocardiography
|
Rocuronium, Neuromuscular Nondepolarizing Agents, Neuromuscular Blocking Agents, Neuromuscular Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Deep Neuromuscular Block (NMB)<br>Muscle paralysis with rocuronium 0.6 - 1.2 mg/kg with the dose adjusted to achieve 1-2 post-tetanic counts (neuromuscular function monitor). | Drug: Rocuronium<br>* Rocuronium 0.6 - 1.2 mg/kg with the dose adjusted to achieve 1-2 post-tetanic counts (Deep NMB) or 1-2 twitches in the train-on-four (Moderate NMB).<br>* Other names: Zemuron;|
| Active Comparator: Moderate Neuromuscular block (NMB)<br>Muscle paralysis with rocuronium 0.6 - 1.2 mg/kg with the dose adjusted to achieve 1-2 twitches in the train-on-four (neuromuscular function monitor). | Drug: Rocuronium<br>* Rocuronium 0.6 - 1.2 mg/kg with the dose adjusted to achieve 1-2 post-tetanic counts (Deep NMB) or 1-2 twitches in the train-on-four (Moderate NMB).<br>* Other names: Zemuron;|
|
Hemodynamic and Respiratory Variations During Laparoscopic Surgery With and Without Deep Neuromuscular Blockade.
Study Overview
=================
Brief Summary
-----------------
The goal of this study is to investigate the effect of depth of neuromuscular block (NMB) on global and regional (dependent versus nondependent) respiratory mechanics during laparoscopic surgery. Furthermore, we will investigate if the level of NMB influences intraoperative hemodynamic and cerebral oxygenation.
Official Title
-----------------
A Prospective, Double-blind, Randomized, Crossover Design Study to Compare the Hemodynamic and Respiratory Variations During Laparoscopic Surgery in Patients With and Without Deep Neuromuscular Blockade.
Conditions
-----------------
Intraoperative Complications, Postoperative Complications, Laparoscopy, Surgical Complications From General Anesthesia, Ventilator-Induced Lung Injury
Intervention / Treatment
-----------------
* Drug: Rocuronium
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18 years or older Elective patients scheduled to undergo laparoscopic surgery with expected duration > 2h Physical status ASA I - III Exclusion Criteria: Pregnancy Severe cardiac disease (NYHA class III or IV, acute coronary syndrome, or persistent ventricular tachyarrhythmia) Previous lung surgery History of severe chronic obstructive pulmonary disease Gastro-esophageal pathology (including but not limited to recent gastric or esophageal surgery including bypass/banding, history of esophageal varices, known anatomical gastric or esophageal defects such as strictures, hernias or fistulas) Mechanical ventilation within the last 30 days Neuromuscular disease Consented for another interventional study or refusal to participate in the present study Hypersensitivity (e.g., anaphylaxis) to rocuronium bromide or other neuromuscular blocking agents
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Deep Neuromuscular Block (NMB)<br>Muscle paralysis with rocuronium 0.6 - 1.2 mg/kg with the dose adjusted to achieve 1-2 post-tetanic counts (neuromuscular function monitor). | Drug: Rocuronium<br>* Rocuronium 0.6 - 1.2 mg/kg with the dose adjusted to achieve 1-2 post-tetanic counts (Deep NMB) or 1-2 twitches in the train-on-four (Moderate NMB).<br>* Other names: Zemuron;|
| Active Comparator: Moderate Neuromuscular block (NMB)<br>Muscle paralysis with rocuronium 0.6 - 1.2 mg/kg with the dose adjusted to achieve 1-2 twitches in the train-on-four (neuromuscular function monitor). | Drug: Rocuronium<br>* Rocuronium 0.6 - 1.2 mg/kg with the dose adjusted to achieve 1-2 post-tetanic counts (Deep NMB) or 1-2 twitches in the train-on-four (Moderate NMB).<br>* Other names: Zemuron;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Regional Change in Air Content (Delta Z, %) | We will measure continuous respiratory flows and pressures in the intraoperative period to assess continuously the compliance and resistance of the respiratory system (T1 to T5). In addition, we will use an esophageal balloon to assess esophageal pressures and partition the global mechanical properties of the respiratory system, into their lung and chest wall components (T1 to T5). Regional lung aeration will be assessed for quantification of intraoperative lung recruitment using Electrical Impedance Tomography (EIT) (T0 to T6). Percent change was calculated using electrical impedance measurements obtained at time T0 as reference. | BL; During pneumoperitoneum; Stage w/2 depths neuromuscular blockade targeted - TOF1 and Deep: 1-2 twitches in post-tetanic count (50-Hz tetanus followed by three-second pause and 15 1-Hz stimuli); and immediately after release of pneumoperitoneum |
| Ejection Fraction (%) | To assess cardiac performance, transthoracic echocardiography will be used. Ejection fraction was measured as fractional shortening (FS). FS is the fraction of any diastolic dimension that is lost in systole. FS = 100*(LVEDD - LVESD) / LVEDD, LVEDD = LV end-diastolic dimension (mm); LVESD = LV end-systolic dimension (mm). | BL; During pneumoperitoneum; Stage w/2 depths neuromuscular blockade targeted - TOF1 and Deep: 1-2 twitches in post-tetanic count (50-Hz tetanus followed by three-second pause and 15 1-Hz stimuli); and immediately after release of pneumoperitoneum |
| Cerebral Oximetry (%) | Regional cerebral oxygenation will be assessed continuously during the intraoperative period using NIRS technology. | BL; During pneumoperitoneum; Stage w/2 depths neuromuscular blockade targeted - TOF1 and Deep: 1-2 twitches in post-tetanic count (50-Hz tetanus followed by three-second pause and 15 1-Hz stimuli); and immediately after release of pneumoperitoneum |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative Pain | The patient will be inquired about pain with a visual analogue scale (VAS). Pain will be evaluated as incisional pain using VAS (0 = no pain; 100 = worst possible pain). | Postoperative Day 1 |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Tomography, Oximetry, Echocardiography
|
|
NCT01678638
|
Timing of Inguinal Hernia Repair in Premature Infants
|
The purpose of this study is to determine whether early (before NICU discharge) or late (55-60 weeks post-menstrual age) inguinal hernia repair is safer for premature infants who have an inguinal hernia.
|
This is a randomized clinical trial comparing early versus late repair in premature infants with an inguinal hernia (IH) to determine which approach may be safer. Safety in this trial is defined as the freedom from significant adverse events, a reduction in hospital days during the study period, and normal neurodevelopmental testing at 2 years. Costs of each treatment strategy are also important and are being evaluated.
|
Timing of Inguinal Hernia Repair in Premature Infants: A Randomized Trial
|
Inguinal Hernia, Premature Birth of Newborn
|
* Procedure: IH repair before NICU discharge
* Procedure: IH repair at 55-60 weeks post-menstrual age
|
Inclusion Criteria:~Infant with estimated gestational age at birth of < 37 weeks, 0 days~In a NICU at participating site~Diagnosed with an IH per the pediatric surgery team~Parents and providers willing to randomize the infant~Exclusion Criteria:~Infant is undergoing another operative procedure and IH repair is planned as a secondary procedure (e.g. fundoplication or G tube is planned, and IH repair is considered a secondary procedure)~Known major congenital anomaly that impacts neurodevelopmental outcome or chromosomal abnormality~Family unable to return for follow up and later IH repair; or likely unable to monitor IH as outpatient
| null |
37 Weeks
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Significant adverse event (SAE) rate | Specific significant adverse events that are either treatment related or hernia related have been defined a priori and will be assessed in both groups from randomization until 9 months after NICU discharge. | 9 months beyond NICU discharge |
| Number of hospital days | Total number of hospital days | From randomization until 9 months post NICU discharge |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital costs | Departmental level costs at each participating institution will be determined for care that occurs from randomization until 9 months post NICU discharge. | Enrollment through 9 months after NICU discharge |
| Bayley Scales of Infant Development, 3rd Edition | Mean BSID scores; primarily cognitive domain | 22-26 months corrected age |
|
inguinal hernia, premature infants, anesthesia safety, neurodevelopmental outcome, preterm infants, neonatal prematurity
|
Premature Birth, Hernia, Hernia, Inguinal, Pathological Conditions, Anatomical, Obstetric Labor, Premature, Obstetric Labor Complications, Pregnancy Complications, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases, Hernia, Abdominal
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Early inguinal hernia (IH) repair<br>IH repair before NICU discharge | Procedure: IH repair before NICU discharge<br>* The IH repair is performed prior to NICU discharge (within 1-2 weeks of enrollment and randomization)<br>|
| Active Comparator: Late inguinal hernia (IH) repair<br>IH repair as outpatient at approximately 55-60 weeks post-menstrual age | Procedure: IH repair at 55-60 weeks post-menstrual age<br>* The IH repair will be performed as an outpatient between approximately 55-60 weeks post-menstrual age.<br>|
|
Timing of Inguinal Hernia Repair in Premature Infants
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether early (before NICU discharge) or late (55-60 weeks post-menstrual age) inguinal hernia repair is safer for premature infants who have an inguinal hernia.
Detailed Description
-----------------
This is a randomized clinical trial comparing early versus late repair in premature infants with an inguinal hernia (IH) to determine which approach may be safer. Safety in this trial is defined as the freedom from significant adverse events, a reduction in hospital days during the study period, and normal neurodevelopmental testing at 2 years. Costs of each treatment strategy are also important and are being evaluated.
Official Title
-----------------
Timing of Inguinal Hernia Repair in Premature Infants: A Randomized Trial
Conditions
-----------------
Inguinal Hernia, Premature Birth of Newborn
Intervention / Treatment
-----------------
* Procedure: IH repair before NICU discharge
* Procedure: IH repair at 55-60 weeks post-menstrual age
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Infant with estimated gestational age at birth of < 37 weeks, 0 days In a NICU at participating site Diagnosed with an IH per the pediatric surgery team Parents and providers willing to randomize the infant Exclusion Criteria: Infant is undergoing another operative procedure and IH repair is planned as a secondary procedure (e.g. fundoplication or G tube is planned, and IH repair is considered a secondary procedure) Known major congenital anomaly that impacts neurodevelopmental outcome or chromosomal abnormality Family unable to return for follow up and later IH repair; or likely unable to monitor IH as outpatient
Ages Eligible for Study
-----------------
Maximum Age: 37 Weeks
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Early inguinal hernia (IH) repair<br>IH repair before NICU discharge | Procedure: IH repair before NICU discharge<br>* The IH repair is performed prior to NICU discharge (within 1-2 weeks of enrollment and randomization)<br>|
| Active Comparator: Late inguinal hernia (IH) repair<br>IH repair as outpatient at approximately 55-60 weeks post-menstrual age | Procedure: IH repair at 55-60 weeks post-menstrual age<br>* The IH repair will be performed as an outpatient between approximately 55-60 weeks post-menstrual age.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Significant adverse event (SAE) rate | Specific significant adverse events that are either treatment related or hernia related have been defined a priori and will be assessed in both groups from randomization until 9 months after NICU discharge. | 9 months beyond NICU discharge |
| Number of hospital days | Total number of hospital days | From randomization until 9 months post NICU discharge |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital costs | Departmental level costs at each participating institution will be determined for care that occurs from randomization until 9 months post NICU discharge. | Enrollment through 9 months after NICU discharge |
| Bayley Scales of Infant Development, 3rd Edition | Mean BSID scores; primarily cognitive domain | 22-26 months corrected age |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
inguinal hernia, premature infants, anesthesia safety, neurodevelopmental outcome, preterm infants, neonatal prematurity
|
NCT05577546
|
The Effect of Conservative Treatment on Gait Biomechanics in Adolescent Idiopathic Scoliosis
|
Adolescent idiopathic scoliosis (AIS) is a three-dimensional complex progressive structural deformity of the growing spine. Asymmetric changes in both the anatomical structure and strength of the muscles due to deformity affect weight distribution and joint moments in the trunk and lower extremities. As the spine transfers loads through the pelvis, asymmetry in the spinal alignment creates structural or functional changes involving other parts of the kinetic chain. The deviations caused by the deformity in all three planes and the responses to it affect the kinetics and kinematics of the trunk and extremities. A number of kinetic and kinematic changes such as decreased hip muscle strength, asymmetric lateral stepping, decreased hip and pelvic joint range of motion, especially in the frontal and transverse planes, and ground reaction force asymmetry has been demonstrated in patients with AIS. Understanding the postural changes and correction strategies that affect the displacement of the center of mass, ground reaction force and center of pressure during standing and walking in adolescents with idiopathic scoliosis is fundamental to understanding the nature of the disease, disease management and guiding rehabilitation both conservative treatment and after surgery. Based on this, it was aimed to objectively measure the biomechanical effects of the forces applied to the body in the brace to control deformity and prevent progression during the growth period, to determine postural control strategies, kinetic and kinematic changes in these patients with treatment by applying MOOR-S model brace and Schroth Three-Dimensional Scoliosis Exercise Treatment as a conservative treatment method on patients with AIS. In addition, it was also aimed to determine lower extremity inequality by measuring dynamic leg length with gait analysis in individuals with functional leg length discrepancy due to scoliosis.
|
Adolescent idiopathic scoliosis (AIS) is a three-dimensional complex progressive structural deformity of the growing spine. Asymmetric changes in both the anatomical structure and strength of the muscles due to deformity affect weight distribution and joint moments in the trunk and lower extremities. As the spine transfers loads through the pelvis, asymmetry in the spinal alignment creates structural or functional changes involving other parts of the kinetic chain. The deviations caused by the deformity in all three planes and the responses to it affects the kinetics and kinematics of the trunk and extremities. Various postural compensatory strategies emerge to maintain a stable position and energy conservation in deviation of the center of mass. Thorax-pelvis coordination plays an important role in maintaining the stability of the whole body in normal walking, the thorax and pelvis counter-rotate towards each other, minimizing the angular momentum of the trunk. In individuals with idiopathic scoliosis, higher in-phase and lower anti-phase coordination in the transverse planes in walking; less coordination consistency were observed in the transverse and frontal planes compared to healthy controls. Most of the studies on gait in AIS have concluded that there is no significant difference in walking speed, cadence and stride width in scoliosis patients and healthy controls. However, decreased hip and pelvic motion, increased energy consumption for gait, step pattern asymmetry, and ground reaction force asymmetry were observed in patients with AIS. A number of kinetic and kinematic changes such as decreased hip muscle strength, asymmetric lateral stepping, decreased hip and pelvic joint range of motion, especially in the frontal and transverse planes, and ground reaction force asymmetry has been demonstrated in patients with AIS. None of the studies included follow-up, most of them did not use EMG, the relationship with curvature types was not clearly revealed, and no treatment effect and follow-up results were evaluated. With this study, the deficiency in the literature will be tried to be overcome, especially in terms of the effect of conservative treatment on gait. Understanding the postural changes and correction strategies that affect the displacement of the center of mass, ground reaction force and center of pressure during standing and walking in adolescents with idiopathic scoliosis is fundamental to understanding the nature of the disease, disease management and guiding rehabilitation both conservative treatment and after surgery. Based on this, it was aimed to objectively measure the biomechanical effects of the forces applied to the body in the brace to control deformity and prevent progression during the growth period, to determine postural control strategies, kinetic and kinematic changes in these patients with treatment by applying MOOR-S model brace and Schroth Three-Dimensional Scoliosis Exercise Treatment as a conservative treatment method on patients with AIS. In addition, it was also aimed to determine lower extremity inequality by measuring dynamic leg length with gait analysis in individuals with functional leg length discrepancy due to scoliosis. Individuals who are diagnosed with AIS and decided to treat a brace, Cobb angle between 20-45 degree and age between 10-18, will be included in the study. Participants will be divided into three groups. The first group will receive MOOR-S brace treatment, the second group will receive the MOOR-S brace and Schroth Three-Dimensional Scoliosis Exercise Treatment, and the third group will not receive any intervention, this group will consist of healthy volunteers from the same age group. Full-time brace treatment will be given to the treatment groups for three months and the second group will be given a home exercise program four days a week and they will perform once a week under physiotherapist supervision. The body center of mass, ground reaction force, range of motion, joint moments and strengths, spinal flexibility, muscle activity in gait, dynamic deviation of the rotational trunk-pelvis segment position, position and orientation of the body segments in three planes, will determine statically and dynamically when they walking, it will be analyzed before and after three months treatment, patients with AIS will be compared with their healthy peers, and the effects of treatment on gait will be determined in the study sample.
|
The Effect of Conservative Treatment on Gait Biomechanics in Adolescent Idiopathic Scoliosis
|
Adolescent Idiopathic Scoliosis, Gait Disorder, Sensorimotor
|
* Other: Moor S brace treatment
* Other: Schroth Three-Dimensional Scoliosis Exercise Treatment
|
Inclusion Criteria:~Patients, diagnosed with AIS and referred to brace center for conservative treatment by the physician~Cobb angle between of 20-45°~ages 10 to 18 years~no treatment before~Individuals with family consent will be included~Exclusion Criteria:~Spine surgery~A history of major lower extremity trauma and associated surgery~Leg length inequality more than 1 cm~Other musculoskeletal pathologies that may affect gait~Presence of transitional vertebrae~Scoliosis due to other etiology~Presence of infection, tumor, rheumatic and neurological disease which affected spine
|
10 Years
|
18 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body center of mass | Body center of mass and its displacement with the brace will assess with computerized 3D gait analysis: With the optoelectronic motion capture system by Qualisys Motion Capture System (Gothenburg, Sweden), assessments will be made with the bare feet while standing and walking. Walking speed is chosen by each individual. Six walking trials will be recorded for each individual on a 15-meter walking path. The system integrated with wireless EMG (Wireless EMG system Delsys) and force platforms (AMTI) has 12 high-resolution cameras and allows the sensing of movement in three planes by Gait Module for Qualisys Track Manager software with the help of marker placed on specific anatomical reference points in the body. Instituti Orthopedici Rizzoli (IOR) Full Body marker protocol was chosen to specify anatomical landmarks. | Change from baseline body center of mass at 3 months |
| Center of pressure | The Center of pressure and its displacement with the brace will assess with computerized 3D gait analysis: With the optoelectronic motion capture system by Qualisys Motion Capture System (Gothenburg, Sweden), assessments will be made with the bare feet while standing and walking. Walking speed is chosen by each individual. Six walking trials will be recorded for each individual on a 15-meter walking path. The system integrated with wireless EMG (Wireless EMG system Delsys) and force platforms (AMTI) has 12 high-resolution cameras and allows the sensing of movement in three planes by Gait Module for Qualisys Track Manager software with the help of marker placed on specific anatomical reference points in the body. Instituti Orthopedici Rizzoli (IOR) Full Body marker protocol was chosen to specify anatomical landmarks. Markers will be placed bilaterally at points on the extremity and both sides of the body. | Change from baseline center of pressure at 3 months |
| Thorax-pelvis coordination pattern | The dynamic deviation of the rotational thorax-pelvis segment position relative to the progression line will be measured. Thorax-pelvis coordination will reveal the relative rotational range of motion between the head, pelvis and upper body in the coordinate system with the information obtained from the relevant anatomical reference points as in the literature. Thorax-pelvis coordination pattern will assess with computerized 3D gait analysis: With the optoelectronic motion capture system by Qualisys Motion Capture System, assessments will be made with bare feet while standing and walking. The system integrated with wireless EMG and force platforms (AMTI) has 12 high-resolution cameras and allows the sensing of movement in three planes by Gait Module for Qualisys Track Manager software with the help of markers placed on specific anatomical reference points in the body. | Change from baseline thorax-pelvis coordination pattern at 3 months |
| Dynamic leg length | Dynamic leg length is the effective length of the lower limb, measured by the distance from the hip joint center to the heel, ankle joint center and forefoot, in order to determine possible functional LLD. Measuring dynamic leg length during the gait cycle takes into account the bony segmental length (foot segment, shank segment, thigh segment) and kinematic angles of the lower extremity in the sagittal, frontal and horizontal plane. Dynamic leg length will assess with computerized 3D gait analysis: With the optoelectronic motion capture system by Qualisys Motion Capture System (Gothenburg, Sweden), assessments will be made with bare feet while standing and walking. The system integrated with wireless EMG and force platforms (AMTI) has 12 high-resolution cameras and allows the sensing of movement in three planes by Gait Module for Qualisys Track Manager software with the help of marker placed on specific anatomical reference points in the body. | Change from baseline dynamic leg length at 3 months |
| Trunk, pelvis and lower extremity kinetics | Using anthropometric measurements, kinematic data and ground reaction force data, joints moments and forces will be calculated with the inverse dynamics method. Body kinetics (kinetic analysis) includes:~Ground reaction force: It will be measured in three planes as mediolateral, vertical and anteroposterior with the force platform of the system.~Net moment (Nm/kg): The signals received from the muscles will be recorded by superficial EMG. As a result of the internal moment and external moment, the net moment and the flexor and extensor moment related to the dominant muscle group will be revealed.~Power: The data obtained from the negative and positive mechanical power graphs will be examined concentric or eccentric contraction and power generation or absorption of the muscles.~Body kinetics (kinetic analysis) will assess with computerized 3D gait analysis: With the optoelectronic motion capture system by Qualisys Motion Capture System | Change from baseline trunk, pelvis and lower extremity kinetics at 3 months |
| Trunk, pelvis and lower extremity kinematics | Body kinematics (kinematic analysis): The position and orientation of the relevant body segments will be measured according to the global coordinate system using the information from the markers and anthropometric data. Through kinematic analysis, joint angles of the head, trunk and extremities in three planes in different phases of gait will be measured. Body kinematics will assess with computerized 3D gait analysis: With the optoelectronic motion capture system by Qualisys Motion Capture System (Gothenburg, Sweden), assessments will be made with bare feet while standing and walking. The system integrated with wireless EMG (Wireless EMG system Delsys) and force platforms (AMTI) has 12 high-resolution cameras and allows the sensing of movement in three planes by Gait Module for Qualisys Track Manager software with the help of marker placed on specific anatomical reference points in the body. | Change from baseline trunk, pelvis and lower extremity kinematics at 3 months |
| Time-distance parameters of gait | Time-distance parameters will be measured with the data obtained from the kinematic data and force platforms.~Walking speed~Cadence~Single and double stride length~Stance and swing time~Single and double support time~Walk-Ratio Time-distance parameters will assess with computerized 3D gait analysis: With the optoelectronic motion capture system by Qualisys Motion Capture System (Gothenburg, Sweden), assessments will be made with bare feet while standing and walking. Walking speed is chosen by each individual. Six walking trials will be recorded for each individual on a 15-meter walking path. The system integrated with wireless EMG (Wireless EMG system Delsys) and force platforms (AMTI) has 12 high-resolution cameras and allows the sensing of movement in three planes by Gait Module for Qualisys Track Manager software with the help of marker placed on specific anatomical reference points in the body. | Change from baseline time-distance parameters of gait at 3 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The angle of trunk rotation | The angle of trunk rotation will be measured by the scoliometer between T1-S1, and the highest value obtained in each part of the spine will be recorded. The angle of trunk rotation indicates the deviation in the transverse plane caused by vertebral rotation in that segment. The scoliometer developed by Orthopedics Systems Incorporation® will be used for the measurements. | Change from baseline the angle of trunk rotation at 3 months |
| Cobb angle | Cobb angle is the sum of upper and lower end vertebra tilt angles in standing anterioposterior radiography. The included angle of the upper vertebra endplate line with the horizontal line is measured on the imaging data and the included angle of the lower vertebra endplate line with the horizontal line is measured on the imaging data. | Baseline |
| Risser stage | The Risser sign is an indirect measure of skeletal maturity, whereby the degree of ossification of the iliac apophysis by x-ray evaluation is used to judge overall skeletal development. Risser stage will be defined using patients spine radiography and physician report. Risser sign consist 5 stages. Risser 0 indicates an immature skeleton while Risser 5 indicates a mature skeleton. | Baseline |
| Deformity classification | Curvature classification will be defined using patients' spine radiography and physician report. Deformity classification will be given as in the gait analysis studies in the literature, indicating a direction and localization in the form of curvature as single thoracic, single lumbar/thoracolumbar and double major | Baseline |
| Generalised joint hypermobility | The presence of generalised joint hypermobility will be evaluated with the nine-point Beighton test using the cut-off ≥5 points. Evaluation consists of five parameters; the first 4 items are evaluated symmetrically in all extremities and 1 point is given for each movement that can be performed. The 5th item is evaluated as 1 point: hyperextension of the MCP joint of the fifth finger >90∘; abduction of the thumb to the forearm; elbow hyperextension >10∘; knee hyperextension >10∘; and touching the floor with the palms of the hands during trunk forward bend performed in a standing position | Baseline |
| Health Related Quality of life | Quality of life in patients with AIS will be assessed using the SRS-22 Questionnaire. SRS-22 was developed by the Scoliosis Research Society to evaluate health-related quality of life (HRQL) in patients with adolescent idiopathic scoliosis (AIS). The SRS-22 questionnaire consists of 22 items Likert type scale that allows scoring between 1-5 for each question. SRS-22 has five domains including function, pain, mental health, self-image and satisfaction. Subgroups can be evaluated separately, or the total score is obtained by summing up the scores from all questions. The total score of each section ranges from 5 to 25, only the section evaluating satisfaction from the treatment is in the range of 2-10. Scoring is obtained by dividing the total score of each section by the number of questions in that section. Higher scores indicate better quality of life. | Change from baseline health related quality of life at 3 months |
|
adolescent idiopathic scoliosis, gait analysis, gait biomechanics, kinetic, kinematic
|
Scoliosis, Gait Disorders, Neurologic, Spinal Curvatures, Spinal Diseases, Bone Diseases, Musculoskeletal Diseases, Neurologic Manifestations, Nervous System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brace group<br>Fifteen patients with AIS will be included in this group. The scoliosis brace, whose characteristics are described below under the Brace heading, will be worn by the patient for 12 weeks. Although the daily brace wearing time varies between 20-23 hours, depending on the patient, it will be determined according to the physician's recommendation. Compliance regarding the brace will be monitored from the parent-controlled charts where the daily wearing time is recorded by the patient | Other: Moor S brace treatment<br>* The rigid MOOR-S Brace controls the thoracic, lumbar and pelvis blocks very tightly, is modelled and produced according to deformity type and patients body size considering the standardization of the MOOR-S Model. It is a CAD-CAM design-based rigid torocolumbosacral orthosis, using polypropylene material, which is opened from the front, and tightness can be adjusted by the patients with the help of straps. Additional corrective forces can be applied with pads that can be added to the brace. The amount of corrective forces in the MOOR-S brace is decided by the experienced orthotist, taking into account risk of progression, the flexibility of the spine deformity, Cobb angle, bone maturation and age. An external stimulus is provided that directs the protracted shoulder to slightly to the posterior by the shoulder part, located on the anterosuperior side of the brace.<br>|
| Experimental: Brace and Schroth exercise group<br>Fifteen patients with AIS will be included in this group, they will be treated by brace and exercise during 12 weeks. The same brace treatment protocol as the brace group will be applied for this group. Additionally, Schroth Three-Dimensional Scoliosis Exercise Treatment will be applied to this group by the researcher physiotherapist at the brace center. Exercise therapy will be carried out at the brace center once a week with the researcher physiotherapist, and 45 min a day, 4 days a week in the form of home exercises. The number of exercise sets and repetitions will be determined by the researcher physiotherapist according to the patient, considering deformity severity and flexibility, generalized joint hypermobility, bone maturation, menarche status and the risk of progression. Compliance with the home exercise program (frequency and duration) will be recorded by the patients in a home exercise diary for 12 weeks. | Other: Moor S brace treatment<br>* The rigid MOOR-S Brace controls the thoracic, lumbar and pelvis blocks very tightly, is modelled and produced according to deformity type and patients body size considering the standardization of the MOOR-S Model. It is a CAD-CAM design-based rigid torocolumbosacral orthosis, using polypropylene material, which is opened from the front, and tightness can be adjusted by the patients with the help of straps. Additional corrective forces can be applied with pads that can be added to the brace. The amount of corrective forces in the MOOR-S brace is decided by the experienced orthotist, taking into account risk of progression, the flexibility of the spine deformity, Cobb angle, bone maturation and age. An external stimulus is provided that directs the protracted shoulder to slightly to the posterior by the shoulder part, located on the anterosuperior side of the brace.<br>Other: Schroth Three-Dimensional Scoliosis Exercise Treatment<br>* Schroth Three-Dimensional Scoliosis Exercise Treatment has the main features of physiotherapeutic scoliosis-specific exercises: 1) Three-dimensional self-correction, 2) Training activities of daily living (ADL), and 3) Stabilization of the corrected posture. The basic principles of the Schroth method are autoelongation, deflection, derotation, rotational angular breathing and stabilization. Exercise therapy will be carried out at the brace center once a week with the researcher, and 45 min a day, 4 days a week in the form of home exercises. The number of exercise sets and repetitions will be determined by the physiotherapist according to the patient, considering deformity severity and flexibility, generalized joint hypermobility, bone maturation, menarche status and the risk of progression. Compliance with the home exercise program (frequency and duration) will be recorded by the patients in a home exercise diary for 12 weeks.<br>* Other names: Schroth Therapy;|
| No Intervention: Healthy control group<br>Fifteen healthy volunteers between the ages of 10-18 will be included in this group. No intervention will be applied to this group and they will only be assessed, and their findings obtained from the gait analysis will compare with the patient groups. | |
|
The Effect of Conservative Treatment on Gait Biomechanics in Adolescent Idiopathic Scoliosis
Study Overview
=================
Brief Summary
-----------------
Adolescent idiopathic scoliosis (AIS) is a three-dimensional complex progressive structural deformity of the growing spine. Asymmetric changes in both the anatomical structure and strength of the muscles due to deformity affect weight distribution and joint moments in the trunk and lower extremities. As the spine transfers loads through the pelvis, asymmetry in the spinal alignment creates structural or functional changes involving other parts of the kinetic chain. The deviations caused by the deformity in all three planes and the responses to it affect the kinetics and kinematics of the trunk and extremities. A number of kinetic and kinematic changes such as decreased hip muscle strength, asymmetric lateral stepping, decreased hip and pelvic joint range of motion, especially in the frontal and transverse planes, and ground reaction force asymmetry has been demonstrated in patients with AIS. Understanding the postural changes and correction strategies that affect the displacement of the center of mass, ground reaction force and center of pressure during standing and walking in adolescents with idiopathic scoliosis is fundamental to understanding the nature of the disease, disease management and guiding rehabilitation both conservative treatment and after surgery. Based on this, it was aimed to objectively measure the biomechanical effects of the forces applied to the body in the brace to control deformity and prevent progression during the growth period, to determine postural control strategies, kinetic and kinematic changes in these patients with treatment by applying MOOR-S model brace and Schroth Three-Dimensional Scoliosis Exercise Treatment as a conservative treatment method on patients with AIS. In addition, it was also aimed to determine lower extremity inequality by measuring dynamic leg length with gait analysis in individuals with functional leg length discrepancy due to scoliosis.
Detailed Description
-----------------
Adolescent idiopathic scoliosis (AIS) is a three-dimensional complex progressive structural deformity of the growing spine. Asymmetric changes in both the anatomical structure and strength of the muscles due to deformity affect weight distribution and joint moments in the trunk and lower extremities. As the spine transfers loads through the pelvis, asymmetry in the spinal alignment creates structural or functional changes involving other parts of the kinetic chain. The deviations caused by the deformity in all three planes and the responses to it affects the kinetics and kinematics of the trunk and extremities. Various postural compensatory strategies emerge to maintain a stable position and energy conservation in deviation of the center of mass. Thorax-pelvis coordination plays an important role in maintaining the stability of the whole body in normal walking, the thorax and pelvis counter-rotate towards each other, minimizing the angular momentum of the trunk. In individuals with idiopathic scoliosis, higher in-phase and lower anti-phase coordination in the transverse planes in walking; less coordination consistency were observed in the transverse and frontal planes compared to healthy controls. Most of the studies on gait in AIS have concluded that there is no significant difference in walking speed, cadence and stride width in scoliosis patients and healthy controls. However, decreased hip and pelvic motion, increased energy consumption for gait, step pattern asymmetry, and ground reaction force asymmetry were observed in patients with AIS. A number of kinetic and kinematic changes such as decreased hip muscle strength, asymmetric lateral stepping, decreased hip and pelvic joint range of motion, especially in the frontal and transverse planes, and ground reaction force asymmetry has been demonstrated in patients with AIS. None of the studies included follow-up, most of them did not use EMG, the relationship with curvature types was not clearly revealed, and no treatment effect and follow-up results were evaluated. With this study, the deficiency in the literature will be tried to be overcome, especially in terms of the effect of conservative treatment on gait. Understanding the postural changes and correction strategies that affect the displacement of the center of mass, ground reaction force and center of pressure during standing and walking in adolescents with idiopathic scoliosis is fundamental to understanding the nature of the disease, disease management and guiding rehabilitation both conservative treatment and after surgery. Based on this, it was aimed to objectively measure the biomechanical effects of the forces applied to the body in the brace to control deformity and prevent progression during the growth period, to determine postural control strategies, kinetic and kinematic changes in these patients with treatment by applying MOOR-S model brace and Schroth Three-Dimensional Scoliosis Exercise Treatment as a conservative treatment method on patients with AIS. In addition, it was also aimed to determine lower extremity inequality by measuring dynamic leg length with gait analysis in individuals with functional leg length discrepancy due to scoliosis. Individuals who are diagnosed with AIS and decided to treat a brace, Cobb angle between 20-45 degree and age between 10-18, will be included in the study. Participants will be divided into three groups. The first group will receive MOOR-S brace treatment, the second group will receive the MOOR-S brace and Schroth Three-Dimensional Scoliosis Exercise Treatment, and the third group will not receive any intervention, this group will consist of healthy volunteers from the same age group. Full-time brace treatment will be given to the treatment groups for three months and the second group will be given a home exercise program four days a week and they will perform once a week under physiotherapist supervision. The body center of mass, ground reaction force, range of motion, joint moments and strengths, spinal flexibility, muscle activity in gait, dynamic deviation of the rotational trunk-pelvis segment position, position and orientation of the body segments in three planes, will determine statically and dynamically when they walking, it will be analyzed before and after three months treatment, patients with AIS will be compared with their healthy peers, and the effects of treatment on gait will be determined in the study sample.
Official Title
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The Effect of Conservative Treatment on Gait Biomechanics in Adolescent Idiopathic Scoliosis
Conditions
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Adolescent Idiopathic Scoliosis, Gait Disorder, Sensorimotor
Intervention / Treatment
-----------------
* Other: Moor S brace treatment
* Other: Schroth Three-Dimensional Scoliosis Exercise Treatment
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients, diagnosed with AIS and referred to brace center for conservative treatment by the physician Cobb angle between of 20-45° ages 10 to 18 years no treatment before Individuals with family consent will be included Exclusion Criteria: Spine surgery A history of major lower extremity trauma and associated surgery Leg length inequality more than 1 cm Other musculoskeletal pathologies that may affect gait Presence of transitional vertebrae Scoliosis due to other etiology Presence of infection, tumor, rheumatic and neurological disease which affected spine
Ages Eligible for Study
-----------------
Minimum Age: 10 Years
Maximum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brace group<br>Fifteen patients with AIS will be included in this group. The scoliosis brace, whose characteristics are described below under the Brace heading, will be worn by the patient for 12 weeks. Although the daily brace wearing time varies between 20-23 hours, depending on the patient, it will be determined according to the physician's recommendation. Compliance regarding the brace will be monitored from the parent-controlled charts where the daily wearing time is recorded by the patient | Other: Moor S brace treatment<br>* The rigid MOOR-S Brace controls the thoracic, lumbar and pelvis blocks very tightly, is modelled and produced according to deformity type and patients body size considering the standardization of the MOOR-S Model. It is a CAD-CAM design-based rigid torocolumbosacral orthosis, using polypropylene material, which is opened from the front, and tightness can be adjusted by the patients with the help of straps. Additional corrective forces can be applied with pads that can be added to the brace. The amount of corrective forces in the MOOR-S brace is decided by the experienced orthotist, taking into account risk of progression, the flexibility of the spine deformity, Cobb angle, bone maturation and age. An external stimulus is provided that directs the protracted shoulder to slightly to the posterior by the shoulder part, located on the anterosuperior side of the brace.<br>|
| Experimental: Brace and Schroth exercise group<br>Fifteen patients with AIS will be included in this group, they will be treated by brace and exercise during 12 weeks. The same brace treatment protocol as the brace group will be applied for this group. Additionally, Schroth Three-Dimensional Scoliosis Exercise Treatment will be applied to this group by the researcher physiotherapist at the brace center. Exercise therapy will be carried out at the brace center once a week with the researcher physiotherapist, and 45 min a day, 4 days a week in the form of home exercises. The number of exercise sets and repetitions will be determined by the researcher physiotherapist according to the patient, considering deformity severity and flexibility, generalized joint hypermobility, bone maturation, menarche status and the risk of progression. Compliance with the home exercise program (frequency and duration) will be recorded by the patients in a home exercise diary for 12 weeks. | Other: Moor S brace treatment<br>* The rigid MOOR-S Brace controls the thoracic, lumbar and pelvis blocks very tightly, is modelled and produced according to deformity type and patients body size considering the standardization of the MOOR-S Model. It is a CAD-CAM design-based rigid torocolumbosacral orthosis, using polypropylene material, which is opened from the front, and tightness can be adjusted by the patients with the help of straps. Additional corrective forces can be applied with pads that can be added to the brace. The amount of corrective forces in the MOOR-S brace is decided by the experienced orthotist, taking into account risk of progression, the flexibility of the spine deformity, Cobb angle, bone maturation and age. An external stimulus is provided that directs the protracted shoulder to slightly to the posterior by the shoulder part, located on the anterosuperior side of the brace.<br>Other: Schroth Three-Dimensional Scoliosis Exercise Treatment<br>* Schroth Three-Dimensional Scoliosis Exercise Treatment has the main features of physiotherapeutic scoliosis-specific exercises: 1) Three-dimensional self-correction, 2) Training activities of daily living (ADL), and 3) Stabilization of the corrected posture. The basic principles of the Schroth method are autoelongation, deflection, derotation, rotational angular breathing and stabilization. Exercise therapy will be carried out at the brace center once a week with the researcher, and 45 min a day, 4 days a week in the form of home exercises. The number of exercise sets and repetitions will be determined by the physiotherapist according to the patient, considering deformity severity and flexibility, generalized joint hypermobility, bone maturation, menarche status and the risk of progression. Compliance with the home exercise program (frequency and duration) will be recorded by the patients in a home exercise diary for 12 weeks.<br>* Other names: Schroth Therapy;|
| No Intervention: Healthy control group<br>Fifteen healthy volunteers between the ages of 10-18 will be included in this group. No intervention will be applied to this group and they will only be assessed, and their findings obtained from the gait analysis will compare with the patient groups. | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body center of mass | Body center of mass and its displacement with the brace will assess with computerized 3D gait analysis: With the optoelectronic motion capture system by Qualisys Motion Capture System (Gothenburg, Sweden), assessments will be made with the bare feet while standing and walking. Walking speed is chosen by each individual. Six walking trials will be recorded for each individual on a 15-meter walking path. The system integrated with wireless EMG (Wireless EMG system Delsys) and force platforms (AMTI) has 12 high-resolution cameras and allows the sensing of movement in three planes by Gait Module for Qualisys Track Manager software with the help of marker placed on specific anatomical reference points in the body. Instituti Orthopedici Rizzoli (IOR) Full Body marker protocol was chosen to specify anatomical landmarks. | Change from baseline body center of mass at 3 months |
| Center of pressure | The Center of pressure and its displacement with the brace will assess with computerized 3D gait analysis: With the optoelectronic motion capture system by Qualisys Motion Capture System (Gothenburg, Sweden), assessments will be made with the bare feet while standing and walking. Walking speed is chosen by each individual. Six walking trials will be recorded for each individual on a 15-meter walking path. The system integrated with wireless EMG (Wireless EMG system Delsys) and force platforms (AMTI) has 12 high-resolution cameras and allows the sensing of movement in three planes by Gait Module for Qualisys Track Manager software with the help of marker placed on specific anatomical reference points in the body. Instituti Orthopedici Rizzoli (IOR) Full Body marker protocol was chosen to specify anatomical landmarks. Markers will be placed bilaterally at points on the extremity and both sides of the body. | Change from baseline center of pressure at 3 months |
| Thorax-pelvis coordination pattern | The dynamic deviation of the rotational thorax-pelvis segment position relative to the progression line will be measured. Thorax-pelvis coordination will reveal the relative rotational range of motion between the head, pelvis and upper body in the coordinate system with the information obtained from the relevant anatomical reference points as in the literature. Thorax-pelvis coordination pattern will assess with computerized 3D gait analysis: With the optoelectronic motion capture system by Qualisys Motion Capture System, assessments will be made with bare feet while standing and walking. The system integrated with wireless EMG and force platforms (AMTI) has 12 high-resolution cameras and allows the sensing of movement in three planes by Gait Module for Qualisys Track Manager software with the help of markers placed on specific anatomical reference points in the body. | Change from baseline thorax-pelvis coordination pattern at 3 months |
| Dynamic leg length | Dynamic leg length is the effective length of the lower limb, measured by the distance from the hip joint center to the heel, ankle joint center and forefoot, in order to determine possible functional LLD. Measuring dynamic leg length during the gait cycle takes into account the bony segmental length (foot segment, shank segment, thigh segment) and kinematic angles of the lower extremity in the sagittal, frontal and horizontal plane. Dynamic leg length will assess with computerized 3D gait analysis: With the optoelectronic motion capture system by Qualisys Motion Capture System (Gothenburg, Sweden), assessments will be made with bare feet while standing and walking. The system integrated with wireless EMG and force platforms (AMTI) has 12 high-resolution cameras and allows the sensing of movement in three planes by Gait Module for Qualisys Track Manager software with the help of marker placed on specific anatomical reference points in the body. | Change from baseline dynamic leg length at 3 months |
| Trunk, pelvis and lower extremity kinetics | Using anthropometric measurements, kinematic data and ground reaction force data, joints moments and forces will be calculated with the inverse dynamics method. Body kinetics (kinetic analysis) includes: Ground reaction force: It will be measured in three planes as mediolateral, vertical and anteroposterior with the force platform of the system. Net moment (Nm/kg): The signals received from the muscles will be recorded by superficial EMG. As a result of the internal moment and external moment, the net moment and the flexor and extensor moment related to the dominant muscle group will be revealed. Power: The data obtained from the negative and positive mechanical power graphs will be examined concentric or eccentric contraction and power generation or absorption of the muscles. Body kinetics (kinetic analysis) will assess with computerized 3D gait analysis: With the optoelectronic motion capture system by Qualisys Motion Capture System | Change from baseline trunk, pelvis and lower extremity kinetics at 3 months |
| Trunk, pelvis and lower extremity kinematics | Body kinematics (kinematic analysis): The position and orientation of the relevant body segments will be measured according to the global coordinate system using the information from the markers and anthropometric data. Through kinematic analysis, joint angles of the head, trunk and extremities in three planes in different phases of gait will be measured. Body kinematics will assess with computerized 3D gait analysis: With the optoelectronic motion capture system by Qualisys Motion Capture System (Gothenburg, Sweden), assessments will be made with bare feet while standing and walking. The system integrated with wireless EMG (Wireless EMG system Delsys) and force platforms (AMTI) has 12 high-resolution cameras and allows the sensing of movement in three planes by Gait Module for Qualisys Track Manager software with the help of marker placed on specific anatomical reference points in the body. | Change from baseline trunk, pelvis and lower extremity kinematics at 3 months |
| Time-distance parameters of gait | Time-distance parameters will be measured with the data obtained from the kinematic data and force platforms. Walking speed Cadence Single and double stride length Stance and swing time Single and double support time Walk-Ratio Time-distance parameters will assess with computerized 3D gait analysis: With the optoelectronic motion capture system by Qualisys Motion Capture System (Gothenburg, Sweden), assessments will be made with bare feet while standing and walking. Walking speed is chosen by each individual. Six walking trials will be recorded for each individual on a 15-meter walking path. The system integrated with wireless EMG (Wireless EMG system Delsys) and force platforms (AMTI) has 12 high-resolution cameras and allows the sensing of movement in three planes by Gait Module for Qualisys Track Manager software with the help of marker placed on specific anatomical reference points in the body. | Change from baseline time-distance parameters of gait at 3 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The angle of trunk rotation | The angle of trunk rotation will be measured by the scoliometer between T1-S1, and the highest value obtained in each part of the spine will be recorded. The angle of trunk rotation indicates the deviation in the transverse plane caused by vertebral rotation in that segment. The scoliometer developed by Orthopedics Systems Incorporation® will be used for the measurements. | Change from baseline the angle of trunk rotation at 3 months |
| Cobb angle | Cobb angle is the sum of upper and lower end vertebra tilt angles in standing anterioposterior radiography. The included angle of the upper vertebra endplate line with the horizontal line is measured on the imaging data and the included angle of the lower vertebra endplate line with the horizontal line is measured on the imaging data. | Baseline |
| Risser stage | The Risser sign is an indirect measure of skeletal maturity, whereby the degree of ossification of the iliac apophysis by x-ray evaluation is used to judge overall skeletal development. Risser stage will be defined using patients spine radiography and physician report. Risser sign consist 5 stages. Risser 0 indicates an immature skeleton while Risser 5 indicates a mature skeleton. | Baseline |
| Deformity classification | Curvature classification will be defined using patients' spine radiography and physician report. Deformity classification will be given as in the gait analysis studies in the literature, indicating a direction and localization in the form of curvature as single thoracic, single lumbar/thoracolumbar and double major | Baseline |
| Generalised joint hypermobility | The presence of generalised joint hypermobility will be evaluated with the nine-point Beighton test using the cut-off ≥5 points. Evaluation consists of five parameters; the first 4 items are evaluated symmetrically in all extremities and 1 point is given for each movement that can be performed. The 5th item is evaluated as 1 point: hyperextension of the MCP joint of the fifth finger >90∘; abduction of the thumb to the forearm; elbow hyperextension >10∘; knee hyperextension >10∘; and touching the floor with the palms of the hands during trunk forward bend performed in a standing position | Baseline |
| Health Related Quality of life | Quality of life in patients with AIS will be assessed using the SRS-22 Questionnaire. SRS-22 was developed by the Scoliosis Research Society to evaluate health-related quality of life (HRQL) in patients with adolescent idiopathic scoliosis (AIS). The SRS-22 questionnaire consists of 22 items Likert type scale that allows scoring between 1-5 for each question. SRS-22 has five domains including function, pain, mental health, self-image and satisfaction. Subgroups can be evaluated separately, or the total score is obtained by summing up the scores from all questions. The total score of each section ranges from 5 to 25, only the section evaluating satisfaction from the treatment is in the range of 2-10. Scoring is obtained by dividing the total score of each section by the number of questions in that section. Higher scores indicate better quality of life. | Change from baseline health related quality of life at 3 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
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adolescent idiopathic scoliosis, gait analysis, gait biomechanics, kinetic, kinematic
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NCT01578915
|
A Case Control Study of Women With Multiple Sexual Partners
|
Both population based surveys and more focused research studies indicate that increased numbers of sexual partners and partner concurrency contribute to increased risk for acquisition of sexually transmitted infection (STI), including HIV infection. However, unlike for men, both national and sub-population-based studies consistently find that the great majority of women with or without STIs report only 1-2 sex partners in the preceding year and that a minority of women acknowledge > 3 sex partners over the same period, suggesting that this relatively small proportion of women with higher numbers of sex partners play a disproportionate role in sustaining community STI rates. Despite these observations, surprisingly little is known about women with increased numbers of sexual partners, the factors which contribute to increased partner number, and the potential for those factors to be intervened upon to reduce risk for STI. The implications of these facts for STI/HIV prevention efforts are profound. For instance, interventions that include the implication that target audiences have multiple sex partners might be dismissed as irrelevant by those with single partners. Conversely, interventions targeting women with multiple sex partners may be based on assumptions derived from data which, while representative of the general target audience, may not reflect relevant circumstances for the subset of women with higher numbers of partners.~This study will begin to generate data that will provide critical information on this topic and help inform future development of STI/HIV interventions tailored to womens' individual circumstances and contexts. The investigators hypothesize that women with 4 or more sexual partners during the past year will report higher rates of depression and substance abuse (alcohol and drugs), higher rates of intimate partner violence, less social support, more non-vaginal sex, more same-sex contacts, and higher rates of STIs than women reporting only one sexual partner during the past year.
|
The objectives of this protocol are: (1) To delineate factors that are important modifiable predictors of sexually transmitted infection (STI) risk in the context of increased numbers of sexual partners, comparing those participants with one sexual partner to those with 4 or more sexual partners during the past year. (2) To define the prevalence of infection with Chlamydia, gonorrhea, trichomoniasis, syphilis, genital herpes, and HIV in women reporting one sexual partner in the past year compared to women reporting 4 or more sexual partners during the past year.
|
A Case Control Study of Women With Multiple Sexual Partners Attending the Jefferson County Department of Health Sexually Transmitted Diseases Clinic
|
Sexually Transmitted Diseases
|
Inclusion Criteria:~female,~age 16 years or older,~report of either one sexual partner during the past year or 4 or more sexual partners in the past year,~able to provide written informed consent~Exclusion Criteria:~Drug and/or alcohol intoxication at the time of enrollment,~exhibition of any type of disruptive or unsafe behavior that would not be conducive to participating in this study
|
16 Years
| null |
Female
|
Accepts Healthy Volunteers
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| STI diagnosis | | Day of enrollment |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sexual risk behaviors | | Up to 3 months prior to enrollment |
| Substance use (alcohol and drugs) | | Up to 30 days prior to enrollment |
| History of intimate partner violence | | At any time prior to enrollment |
| Depression | | Up to 7 days prior to enrollment |
| Social support | | Up to 30 days prior to enrollment |
|
Sexually Transmitted Diseases, Communicable Diseases, Infections, Genital Diseases, Urogenital Diseases, Disease Attributes, Pathologic Processes
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cases<br>Women with 4 or more sexual partners during the past year | |
| Controls<br>Women with only one sexual partner during the past year | |
|
A Case Control Study of Women With Multiple Sexual Partners
Study Overview
=================
Brief Summary
-----------------
Both population based surveys and more focused research studies indicate that increased numbers of sexual partners and partner concurrency contribute to increased risk for acquisition of sexually transmitted infection (STI), including HIV infection. However, unlike for men, both national and sub-population-based studies consistently find that the great majority of women with or without STIs report only 1-2 sex partners in the preceding year and that a minority of women acknowledge > 3 sex partners over the same period, suggesting that this relatively small proportion of women with higher numbers of sex partners play a disproportionate role in sustaining community STI rates. Despite these observations, surprisingly little is known about women with increased numbers of sexual partners, the factors which contribute to increased partner number, and the potential for those factors to be intervened upon to reduce risk for STI. The implications of these facts for STI/HIV prevention efforts are profound. For instance, interventions that include the implication that target audiences have multiple sex partners might be dismissed as irrelevant by those with single partners. Conversely, interventions targeting women with multiple sex partners may be based on assumptions derived from data which, while representative of the general target audience, may not reflect relevant circumstances for the subset of women with higher numbers of partners. This study will begin to generate data that will provide critical information on this topic and help inform future development of STI/HIV interventions tailored to womens' individual circumstances and contexts. The investigators hypothesize that women with 4 or more sexual partners during the past year will report higher rates of depression and substance abuse (alcohol and drugs), higher rates of intimate partner violence, less social support, more non-vaginal sex, more same-sex contacts, and higher rates of STIs than women reporting only one sexual partner during the past year.
Detailed Description
-----------------
The objectives of this protocol are: (1) To delineate factors that are important modifiable predictors of sexually transmitted infection (STI) risk in the context of increased numbers of sexual partners, comparing those participants with one sexual partner to those with 4 or more sexual partners during the past year. (2) To define the prevalence of infection with Chlamydia, gonorrhea, trichomoniasis, syphilis, genital herpes, and HIV in women reporting one sexual partner in the past year compared to women reporting 4 or more sexual partners during the past year.
Official Title
-----------------
A Case Control Study of Women With Multiple Sexual Partners Attending the Jefferson County Department of Health Sexually Transmitted Diseases Clinic
Conditions
-----------------
Sexually Transmitted Diseases
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: female, age 16 years or older, report of either one sexual partner during the past year or 4 or more sexual partners in the past year, able to provide written informed consent Exclusion Criteria: Drug and/or alcohol intoxication at the time of enrollment, exhibition of any type of disruptive or unsafe behavior that would not be conducive to participating in this study
Ages Eligible for Study
-----------------
Minimum Age: 16 Years
Sexes Eligible for Study
-----------------
Female
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cases<br>Women with 4 or more sexual partners during the past year | |
| Controls<br>Women with only one sexual partner during the past year | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| STI diagnosis | | Day of enrollment |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sexual risk behaviors | | Up to 3 months prior to enrollment |
| Substance use (alcohol and drugs) | | Up to 30 days prior to enrollment |
| History of intimate partner violence | | At any time prior to enrollment |
| Depression | | Up to 7 days prior to enrollment |
| Social support | | Up to 30 days prior to enrollment |
|
|||
NCT00650195
|
Fasting Study of Metolazone Tablets 10 mg and Zaroloxyn® Tablets 10 mg
|
The objective of this study was to investigate the bioequivalence of Mylan metolazone 10 mg tablets to Celltech Zaroxolyn® 10 mg tablets following a single, oral 10 mg (1 x 10 mg) dose administration under fasting conditions.
|
Single-Dose Fasting In Vivo Bioequivalence Study of Metolazone Tablets (10 mg; Mylan) and Zaroloxyn® Tablets (10 mg; Celltech) in Healthy Volunteers
|
Healthy
|
* Drug: Metolazone Tablets 10 mg
* Drug: Zaroloxyn® Tablets 10 mg
|
Inclusion Criteria:~Age: 18 years and older~Sex: Male and/or non-pregnant, non-lactating female~Women of childbearing potential must have negative serum b-human chorionic gonadotropin (β-HCG) pregnancy tests performed within 14 days prior to the start of the study and on the evening prior to each dose administration. If dosing is scheduled on Sunday or Monday, serum samples for β-HCG testing may be collected and sent for analysis within 48 hours prior to dosing for both study periods. An additional serum (Beta-HCG) pregnancy test will be performed upon completion of the study.~Women of childbearing potential must practice abstinence or use an acceptable form of contraception throughout the duration of the study. No hormonal contraceptives or hormonal replacement therapy are permitted in this study. Acceptable forms of contraception include the following:~intrauterine device in place for at least 3 months prior to the start of the study and remaining in place during the study period, or~barrier methods containing or used in conjunction with a spermicidal agent, or~surgical sterility (tubal ligation, oophorectomy or hysterectomy) or postmenopausal accompanied with a documented postmenopausal course of at least one year.~During the course of the study, from study screen until study exit - including the washout period, women of childbearing potential must use a spermicide containing barrier method of contraception in addition to their current contraceptive device. This advice should be documented in the informed consent form.~Weight: At least 60 kg (132 lbs.) for men and 48 kg (106 lbs.) for women and within 15% of Ideal Body Weight (IBW), as referenced by the Table of Desirable Weights of Adults Metropolitan Life Insurance Company, 1999 (See Part II ADMINISTRATIVE ASPECTS OF BIOEQUIVALENCE PROTOCOLS).~All subjects should be judged normal and healthy during a pre-study medical evaluation (physical examination, laboratory evaluation, 12-lead ECG, Hepatitis B, Hepatitis C and HIV tests and urine drug screen including amphetamine, benzodiazepine, cannabinoid, cocaine, opiate screen and phencyclidine) performed within 14 days of the initial dose of study medication.~Exclusion Criteria:~Institutionalized subjects will not be used.~Social Habits:~Use of any tobacco products within one year prior to dosing.~Ingestion of any alcoholic, caffeine- or xanthine-containing food or beverage within the 48 hours prior to the initial dose of study medication.~Ingestion of any vitamins or herbal products within 7 days prior to the initial dose of the study medication.~Any recent, significant change in dietary or exercise habits.~Medications:~Use of any medication within the last 14 days prior to the initial dose of study medication, including over-the-counter medications.~Use of any medication known to alter hepatic enzyme activity within 28 days prior to the initial dose of study medication.~Use of hormonal contraceptives and hormonal replacement therapy within three months prior to the initial dose of study medication.~Diseases:~History of any significant cardiovascular, hepatic, renal, pulmonary, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic disease.~History of drug and/or alcohol abuse within 1 year prior to the study.~Acute illness at the time of either the pre-study medical evaluation or dosing.~Abnormal and clinically significant laboratory test results:~Any laboratory result deemed a clinically significant deviation by the investigator.~Abnormal and clinically relevant ECG tracing.~Donation or loss of a significant volume of blood or plasma (> 450 mL) within 28 days prior to the initial dose of study medication.~Subjects who have received an investigational drug within 30 days prior to the initial dose of study medication.~Allergy or hypersensitivity to metolazone, sulfonamide-derived drugs, thiazides, quinethazone or other related products.~History of difficulties in swallowing, or any gastrointestinal disease which could affect the drug absorption.~Consumption of grapefruit or grapefruit containing products within 7 days of drug administration.
|
18 Years
| null |
All
|
Accepts Healthy Volunteers
|
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bioequivalence | | within 30 days |
|
Metolazone, Antihypertensive Agents, Diuretics, Natriuretic Agents, Physiological Effects of Drugs, Sodium Chloride Symporter Inhibitors, Membrane Transport Modulators, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Metolazone Tablets 10 mg | Drug: Metolazone Tablets 10 mg<br>* 10mg, single dose fasting<br>|
| Active Comparator: 2<br>Zaroloxyn® Tablets 10 mg | Drug: Zaroloxyn® Tablets 10 mg<br>* 10mg, single dose fasting<br>|
|
Fasting Study of Metolazone Tablets 10 mg and Zaroloxyn® Tablets 10 mg
Study Overview
=================
Brief Summary
-----------------
The objective of this study was to investigate the bioequivalence of Mylan metolazone 10 mg tablets to Celltech Zaroxolyn® 10 mg tablets following a single, oral 10 mg (1 x 10 mg) dose administration under fasting conditions.
Official Title
-----------------
Single-Dose Fasting In Vivo Bioequivalence Study of Metolazone Tablets (10 mg; Mylan) and Zaroloxyn® Tablets (10 mg; Celltech) in Healthy Volunteers
Conditions
-----------------
Healthy
Intervention / Treatment
-----------------
* Drug: Metolazone Tablets 10 mg
* Drug: Zaroloxyn® Tablets 10 mg
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age: 18 years and older Sex: Male and/or non-pregnant, non-lactating female Women of childbearing potential must have negative serum b-human chorionic gonadotropin (β-HCG) pregnancy tests performed within 14 days prior to the start of the study and on the evening prior to each dose administration. If dosing is scheduled on Sunday or Monday, serum samples for β-HCG testing may be collected and sent for analysis within 48 hours prior to dosing for both study periods. An additional serum (Beta-HCG) pregnancy test will be performed upon completion of the study. Women of childbearing potential must practice abstinence or use an acceptable form of contraception throughout the duration of the study. No hormonal contraceptives or hormonal replacement therapy are permitted in this study. Acceptable forms of contraception include the following: intrauterine device in place for at least 3 months prior to the start of the study and remaining in place during the study period, or barrier methods containing or used in conjunction with a spermicidal agent, or surgical sterility (tubal ligation, oophorectomy or hysterectomy) or postmenopausal accompanied with a documented postmenopausal course of at least one year. During the course of the study, from study screen until study exit - including the washout period, women of childbearing potential must use a spermicide containing barrier method of contraception in addition to their current contraceptive device. This advice should be documented in the informed consent form. Weight: At least 60 kg (132 lbs.) for men and 48 kg (106 lbs.) for women and within 15% of Ideal Body Weight (IBW), as referenced by the Table of Desirable Weights of Adults Metropolitan Life Insurance Company, 1999 (See Part II ADMINISTRATIVE ASPECTS OF BIOEQUIVALENCE PROTOCOLS). All subjects should be judged normal and healthy during a pre-study medical evaluation (physical examination, laboratory evaluation, 12-lead ECG, Hepatitis B, Hepatitis C and HIV tests and urine drug screen including amphetamine, benzodiazepine, cannabinoid, cocaine, opiate screen and phencyclidine) performed within 14 days of the initial dose of study medication. Exclusion Criteria: Institutionalized subjects will not be used. Social Habits: Use of any tobacco products within one year prior to dosing. Ingestion of any alcoholic, caffeine- or xanthine-containing food or beverage within the 48 hours prior to the initial dose of study medication. Ingestion of any vitamins or herbal products within 7 days prior to the initial dose of the study medication. Any recent, significant change in dietary or exercise habits. Medications: Use of any medication within the last 14 days prior to the initial dose of study medication, including over-the-counter medications. Use of any medication known to alter hepatic enzyme activity within 28 days prior to the initial dose of study medication. Use of hormonal contraceptives and hormonal replacement therapy within three months prior to the initial dose of study medication. Diseases: History of any significant cardiovascular, hepatic, renal, pulmonary, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic disease. History of drug and/or alcohol abuse within 1 year prior to the study. Acute illness at the time of either the pre-study medical evaluation or dosing. Abnormal and clinically significant laboratory test results: Any laboratory result deemed a clinically significant deviation by the investigator. Abnormal and clinically relevant ECG tracing. Donation or loss of a significant volume of blood or plasma (> 450 mL) within 28 days prior to the initial dose of study medication. Subjects who have received an investigational drug within 30 days prior to the initial dose of study medication. Allergy or hypersensitivity to metolazone, sulfonamide-derived drugs, thiazides, quinethazone or other related products. History of difficulties in swallowing, or any gastrointestinal disease which could affect the drug absorption. Consumption of grapefruit or grapefruit containing products within 7 days of drug administration.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Metolazone Tablets 10 mg | Drug: Metolazone Tablets 10 mg<br>* 10mg, single dose fasting<br>|
| Active Comparator: 2<br>Zaroloxyn® Tablets 10 mg | Drug: Zaroloxyn® Tablets 10 mg<br>* 10mg, single dose fasting<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bioequivalence | | within 30 days |
|
|||
NCT00422682
|
A Study Evaluating BSI-201 in Combination With Chemotherapeutic Regimens in Subjects With Advanced Solid Tumors
|
The purpose of the study is to assess the safety and establish the maximum tolerated dose (MTD) of the combination of BSI-201 with chemotherapeutic regimens in adult subjects with histologically or cytologically documented advanced solid tumors.~Based on data generated by BiPar/Sanofi, it is concluded that iniparib does not possess characteristics typical of the PARP inhibitor class. The exact mechanism has not yet been fully elucidated, however based on experiments on tumor cells performed in the laboratory, iniparib is a novel investigational anti-cancer agent that induces gamma-H2AX (a marker of DNA damage) in tumor cell lines, induces cell cycle arrest in the G2/M phase in tumor cell lines, and potentiates the cell cycle effects of DNA damaging modalities in tumor cell lines. Investigations into potential targets of iniparib and its metabolites are ongoing.
|
A Phase 1B, Open-Label, Dose Escalation Study Evaluating the Safety of BSI-201 in Combination With Chemotherapeutic Regimens in Subjects With Advanced Solid Tumors
|
Tumors
|
* Drug: bsi-201 + topotecan
* Drug: bsi-201 + temozolomide
* Drug: bsi-201 + gemcitabine
* Drug: bsi-201 + carboplatin/paclitaxel
|
Inclusion Criteria:~≥ 18 years old with a histologically or cytologically documented, advanced solid tumor~Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1~Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (without granulocyte colony-stimulating factor [G-CSF] support within 2 weeks of study day 1); platelet count ≥ 100.0 x 10^9/L (without transfusion within 2 weeks of study day 1); and hemoglobin ≥ 9.0 g/dL (erythropoietic agents allowed)~At least a 14-day period from end of last dose of chemotherapy received~Any prior toxicity from prior chemotherapeutic treatment recovered to ≤ grade 1~Exclusion Criteria:~Subject enrolled in another investigational device or drug trial, or is receiving other investigational agents~Hematological malignancies~Symptomatic or untreated brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation, and corticosteroids.~History of seizure disorder~Myocardial infarction (MI) within 6 months of study day 1, unstable angina, congestive heart failure (CHF) with New York Heart Association (NYHA) > class II, or uncontrolled hypertension~Concurrent or prior (within 7 days of study day 1) anticoagulation therapy (low dose for port maintenance allowed)~Specified concomitant medications~Serum creatinine > 1.5 x upper limit of normal (ULN)~Elevated liver enzymes (AST/ALT) > 2.5 x ULN, or > 5.0 x ULN if secondary to liver metastases; alkaline phosphatase > 2.5 x ULN or > 5.0 x ULN if secondary to liver or bone metastases; total bilirubin > 1.5 x ULN~Radiation therapy within 14 days of study day 1~Antibody therapy for the treatment of an underlying malignancy within 14 days of study day 1~Concurrent radiation therapy is not permitted throughout the course of the study
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety and efficacy | | ongoing |
| Response rate (CR + PR) | | every 2 cycles |
|
Solid tumors
|
Paclitaxel, Carboplatin, Gemcitabine, Temozolomide, Topotecan, Iniparib, Antineoplastic Agents, Phytogenic, Antineoplastic Agents, Tubulin Modulators, Antimitotic Agents, Mitosis Modulators, Molecular Mechanisms of Pharmacological Action, Antimetabolites, Antineoplastic, Antimetabolites, Antineoplastic Agents, Alkylating, Alkylating Agents, Topoisomerase I Inhibitors, Topoisomerase Inhibitors, Enzyme Inhibitors, Poly(ADP-ribose) Polymerase Inhibitors
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>BSI-201 + topotecan | Drug: bsi-201 + topotecan<br>* 21 day cycle<br>|
| Experimental: 2<br>BSI-201 + temozolomide | Drug: bsi-201 + temozolomide<br>* 28 day cycle<br>|
| Experimental: 3<br>bsi-201 + gemcitabine | Drug: bsi-201 + gemcitabine<br>* 28 day cycle<br>|
| Experimental: 4<br>bsi-201 + carboplatin/paclitaxel | Drug: bsi-201 + carboplatin/paclitaxel<br>* 21 day cycle<br>|
|
A Study Evaluating BSI-201 in Combination With Chemotherapeutic Regimens in Subjects With Advanced Solid Tumors
Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to assess the safety and establish the maximum tolerated dose (MTD) of the combination of BSI-201 with chemotherapeutic regimens in adult subjects with histologically or cytologically documented advanced solid tumors. Based on data generated by BiPar/Sanofi, it is concluded that iniparib does not possess characteristics typical of the PARP inhibitor class. The exact mechanism has not yet been fully elucidated, however based on experiments on tumor cells performed in the laboratory, iniparib is a novel investigational anti-cancer agent that induces gamma-H2AX (a marker of DNA damage) in tumor cell lines, induces cell cycle arrest in the G2/M phase in tumor cell lines, and potentiates the cell cycle effects of DNA damaging modalities in tumor cell lines. Investigations into potential targets of iniparib and its metabolites are ongoing.
Official Title
-----------------
A Phase 1B, Open-Label, Dose Escalation Study Evaluating the Safety of BSI-201 in Combination With Chemotherapeutic Regimens in Subjects With Advanced Solid Tumors
Conditions
-----------------
Tumors
Intervention / Treatment
-----------------
* Drug: bsi-201 + topotecan
* Drug: bsi-201 + temozolomide
* Drug: bsi-201 + gemcitabine
* Drug: bsi-201 + carboplatin/paclitaxel
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: ≥ 18 years old with a histologically or cytologically documented, advanced solid tumor Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (without granulocyte colony-stimulating factor [G-CSF] support within 2 weeks of study day 1); platelet count ≥ 100.0 x 10^9/L (without transfusion within 2 weeks of study day 1); and hemoglobin ≥ 9.0 g/dL (erythropoietic agents allowed) At least a 14-day period from end of last dose of chemotherapy received Any prior toxicity from prior chemotherapeutic treatment recovered to ≤ grade 1 Exclusion Criteria: Subject enrolled in another investigational device or drug trial, or is receiving other investigational agents Hematological malignancies Symptomatic or untreated brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation, and corticosteroids. History of seizure disorder Myocardial infarction (MI) within 6 months of study day 1, unstable angina, congestive heart failure (CHF) with New York Heart Association (NYHA) > class II, or uncontrolled hypertension Concurrent or prior (within 7 days of study day 1) anticoagulation therapy (low dose for port maintenance allowed) Specified concomitant medications Serum creatinine > 1.5 x upper limit of normal (ULN) Elevated liver enzymes (AST/ALT) > 2.5 x ULN, or > 5.0 x ULN if secondary to liver metastases; alkaline phosphatase > 2.5 x ULN or > 5.0 x ULN if secondary to liver or bone metastases; total bilirubin > 1.5 x ULN Radiation therapy within 14 days of study day 1 Antibody therapy for the treatment of an underlying malignancy within 14 days of study day 1 Concurrent radiation therapy is not permitted throughout the course of the study
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>BSI-201 + topotecan | Drug: bsi-201 + topotecan<br>* 21 day cycle<br>|
| Experimental: 2<br>BSI-201 + temozolomide | Drug: bsi-201 + temozolomide<br>* 28 day cycle<br>|
| Experimental: 3<br>bsi-201 + gemcitabine | Drug: bsi-201 + gemcitabine<br>* 28 day cycle<br>|
| Experimental: 4<br>bsi-201 + carboplatin/paclitaxel | Drug: bsi-201 + carboplatin/paclitaxel<br>* 21 day cycle<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety and efficacy | | ongoing |
| Response rate (CR + PR) | | every 2 cycles |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Solid tumors
|
||
NCT02410590
|
Rocuronium + Sugammadex vs. Succinylcholine + Cisatracurium + Neostigmine/Atropine in Obese Participants (MK-8616-104)
|
The primary objective of this trial is to compare the preference between two strategies of neuromuscular blocking (NMB) / reversal in adult obese patients undergoing laparoscopic abdominal surgery: Rocuronium + Sugammadex versus Succinylcholine + Cisatracurium + Neostigmine/Atropine. This will be done evaluating the average verbal numerical scale (VNS) scores obtained from surgeons blinded to the drugs administered. The primary hypothesis is that the strategy Rocuronium + Sugammadex provides a better surgical visual field in obese participants undergoing laparoscopic abdominal surgery than the strategy Succinylcholine + Cisatracurium + Neostigmine/Atropine as measured by VNS scores.
|
Randomized, Parallel Group, Controlled Trial to Compare Two Different NMB + Reversal Strategies in Adult Obese Patients Undergoing Laparoscopic Abdominal Surgery
|
Neuromuscular Blockade
|
* Drug: Rocuronium
* Drug: Sugammadex
* Drug: Cisatracurium
* Drug: Neostigmine/Atropine
* Drug: Succinylcholine
|
Inclusion Criteria:~must be obese, with a Body Mass Index ≥30.0 to ≤50.~must be scheduled to undergo an elective abdominal laparoscopic surgery, under general anesthesia. (Participants are expected to remain in the hospital for at least 24 hours following surgical procedure.)~must be categorized as American Society of Anesthesiologists (ASA) Class 1, 2, or 3.~clinical laboratory tests within normal limits or clinically acceptable to the investigator/sponsor.~sexually active females of child-bearing potential must agree to use a medically accepted method of contraception while receiving protocol-specified medication and for the 30 days after stopping the medication. Medically accepted methods of contraception include condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed IUD, inert or copper-containing IUD, hormone-releasing IUD, systemic hormonal contraceptive, and surgical sterilization (eg, hysterectomy or tubal ligation). Postmenopausal women are not required to use contraception. Postmenopausal is defined as at least 12 consecutive months without a spontaneous menstrual period. Each sexually active male subject with a female partner(s) of childbearing potential must also provide written informed consent to provide information regarding any pregnancy.~Exclusion Criteria:~has anatomical malformations that may lead to difficult intubation.~is known or suspected to have neuromuscular disorders that may affect NMB and/or trial assessments.~history of previous abdominal laparoscopy procedures.~must not currently (within past 6 months) meet DSM-IV-TR criteria for substance abuse or dependence (excluding nicotine).~history of a chronic pain condition (requiring continuous/daily pain medication prior to surgery).~females who have given birth to one or more children in the last 12 months, or are pregnant or intend to become pregnant between randomization and >Day 30 pregnancy follow-up contact [premenopausal female of childbearing potential].~evidence of acute cholecystitis.~dialysis-dependency or suspected of having severe renal insufficiency (defined as estimated creatinine clearance of <30 mL/min).~significant hepatic dysfunction that would prevent participation in the trial, based on the summary of product characteristics of the study drugs.~history of or family history of malignant hyperthermia.~known allergy to trial treatments (rocuronium, sugammadex, succinylcholine, cisatracurium, neostigmine, atropine) or their excipients, to opioids/opiates, or other medication used during general anesthesia.~expected transfer to intensive care unit after surgery.~must continue to receive toremifene or fusidic acid during the trial.~has participated in another clinical trial within 30 days of signing the informed consent form of the current trial.
|
18 Years
| null |
All
|
No
|
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Surgeons who prefer Rocuronium + Sugammadex vs. Succinylcholine + Cisatracurium + Neostigmine/Atropine for neuromuscular blocking/reversal in obese participants undergoing laparoscopic abdominal surgery | | Up to 1 hour after end of surgery |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time elapsed from end of surgery to extubation | | Up to 1 hour after end of surgery |
| Time elapsed from start of reversal drug administration to train-of-four (TOF) ratio ≥0.9 | | Up to 1 hour after start of reversal drug treatment |
|
Neuromuscular Nondepolarizing Agents, Neuromuscular Blocking Agents, Neuromuscular Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Adjuvants, Anesthesia, Anti-Arrhythmia Agents, Bronchodilator Agents, Autonomic Agents, Anti-Asthmatic Agents, Respiratory System Agents, Mydriatics, Parasympatholytics, Muscarinic Antagonists, Atropine, Rocuronium, Cisatracurium, Succinylcholine, Neostigmine, Cholinergic Antagonists, Cholinergic Agents, Neurotransmitter Agents, Molecular Mechanisms of Pharmacological Action, Cholinesterase Inhibitors, Enzyme Inhibitors, Parasympathomimetics, Neuromuscular Depolarizing Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rocuronium + Sugammadex<br>Participants will receive rocuronium administered at a dosage adequate to make intubation possible and provide deep NMB (defined as no response to train-of-four stimulation but at least one response to five post-tetanic count [PTC]) for the duration of surgery, until the end of the procedure. Sugammadex will be administered to participants once at a dosage of 4 mg/kg real body weight (RBW) IV at the end of surgical procedure. Sugammadex will be used as the only reversal drug in all participants who receive rocuronium as a neuromuscular blocker. | Drug: Rocuronium<br> <br> Drug: Sugammadex<br> <br> |
| Active Comparator: Succinylcholine + Cisatracurium + Neostigmine/Atropine<br>After receiving succinylcholine 1.0 mg/kg RBW for intubation, participants will receive cisatracurium administered at dosage adequate to have a moderate NMB (defined as a target of TOF ratio = 10% with a range: 2-3 twitches to TOF ratio of 20%) for the duration of surgery, until the end of the procedure. Neostigmine/Atropine will be administered to participants once at respective dosage of 0.05 mg/kg RBW and 0.01 mg/kg RBW at least after the reappearance of T2 after surgery completion. The maximum allowed dosage for Neostigmine is 5 mg. Neostigmine will be used as only reversal drug in all participants who received Cisatracurium as neuromuscular blocker. | Drug: Cisatracurium<br> <br> Drug: Neostigmine/Atropine<br> <br> Drug: Succinylcholine<br> <br> |
|
Rocuronium + Sugammadex vs. Succinylcholine + Cisatracurium + Neostigmine/Atropine in Obese Participants (MK-8616-104)
Study Overview
=================
Brief Summary
-----------------
The primary objective of this trial is to compare the preference between two strategies of neuromuscular blocking (NMB) / reversal in adult obese patients undergoing laparoscopic abdominal surgery: Rocuronium + Sugammadex versus Succinylcholine + Cisatracurium + Neostigmine/Atropine. This will be done evaluating the average verbal numerical scale (VNS) scores obtained from surgeons blinded to the drugs administered. The primary hypothesis is that the strategy Rocuronium + Sugammadex provides a better surgical visual field in obese participants undergoing laparoscopic abdominal surgery than the strategy Succinylcholine + Cisatracurium + Neostigmine/Atropine as measured by VNS scores.
Official Title
-----------------
Randomized, Parallel Group, Controlled Trial to Compare Two Different NMB + Reversal Strategies in Adult Obese Patients Undergoing Laparoscopic Abdominal Surgery
Conditions
-----------------
Neuromuscular Blockade
Intervention / Treatment
-----------------
* Drug: Rocuronium
* Drug: Sugammadex
* Drug: Cisatracurium
* Drug: Neostigmine/Atropine
* Drug: Succinylcholine
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: must be obese, with a Body Mass Index ≥30.0 to ≤50. must be scheduled to undergo an elective abdominal laparoscopic surgery, under general anesthesia. (Participants are expected to remain in the hospital for at least 24 hours following surgical procedure.) must be categorized as American Society of Anesthesiologists (ASA) Class 1, 2, or 3. clinical laboratory tests within normal limits or clinically acceptable to the investigator/sponsor. sexually active females of child-bearing potential must agree to use a medically accepted method of contraception while receiving protocol-specified medication and for the 30 days after stopping the medication. Medically accepted methods of contraception include condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed IUD, inert or copper-containing IUD, hormone-releasing IUD, systemic hormonal contraceptive, and surgical sterilization (eg, hysterectomy or tubal ligation). Postmenopausal women are not required to use contraception. Postmenopausal is defined as at least 12 consecutive months without a spontaneous menstrual period. Each sexually active male subject with a female partner(s) of childbearing potential must also provide written informed consent to provide information regarding any pregnancy. Exclusion Criteria: has anatomical malformations that may lead to difficult intubation. is known or suspected to have neuromuscular disorders that may affect NMB and/or trial assessments. history of previous abdominal laparoscopy procedures. must not currently (within past 6 months) meet DSM-IV-TR criteria for substance abuse or dependence (excluding nicotine). history of a chronic pain condition (requiring continuous/daily pain medication prior to surgery). females who have given birth to one or more children in the last 12 months, or are pregnant or intend to become pregnant between randomization and >Day 30 pregnancy follow-up contact [premenopausal female of childbearing potential]. evidence of acute cholecystitis. dialysis-dependency or suspected of having severe renal insufficiency (defined as estimated creatinine clearance of <30 mL/min). significant hepatic dysfunction that would prevent participation in the trial, based on the summary of product characteristics of the study drugs. history of or family history of malignant hyperthermia. known allergy to trial treatments (rocuronium, sugammadex, succinylcholine, cisatracurium, neostigmine, atropine) or their excipients, to opioids/opiates, or other medication used during general anesthesia. expected transfer to intensive care unit after surgery. must continue to receive toremifene or fusidic acid during the trial. has participated in another clinical trial within 30 days of signing the informed consent form of the current trial.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rocuronium + Sugammadex<br>Participants will receive rocuronium administered at a dosage adequate to make intubation possible and provide deep NMB (defined as no response to train-of-four stimulation but at least one response to five post-tetanic count [PTC]) for the duration of surgery, until the end of the procedure. Sugammadex will be administered to participants once at a dosage of 4 mg/kg real body weight (RBW) IV at the end of surgical procedure. Sugammadex will be used as the only reversal drug in all participants who receive rocuronium as a neuromuscular blocker. | Drug: Rocuronium<br> <br> Drug: Sugammadex<br> <br> |
| Active Comparator: Succinylcholine + Cisatracurium + Neostigmine/Atropine<br>After receiving succinylcholine 1.0 mg/kg RBW for intubation, participants will receive cisatracurium administered at dosage adequate to have a moderate NMB (defined as a target of TOF ratio = 10% with a range: 2-3 twitches to TOF ratio of 20%) for the duration of surgery, until the end of the procedure. Neostigmine/Atropine will be administered to participants once at respective dosage of 0.05 mg/kg RBW and 0.01 mg/kg RBW at least after the reappearance of T2 after surgery completion. The maximum allowed dosage for Neostigmine is 5 mg. Neostigmine will be used as only reversal drug in all participants who received Cisatracurium as neuromuscular blocker. | Drug: Cisatracurium<br> <br> Drug: Neostigmine/Atropine<br> <br> Drug: Succinylcholine<br> <br> |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Surgeons who prefer Rocuronium + Sugammadex vs. Succinylcholine + Cisatracurium + Neostigmine/Atropine for neuromuscular blocking/reversal in obese participants undergoing laparoscopic abdominal surgery | | Up to 1 hour after end of surgery |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time elapsed from end of surgery to extubation | | Up to 1 hour after end of surgery |
| Time elapsed from start of reversal drug administration to train-of-four (TOF) ratio ≥0.9 | | Up to 1 hour after start of reversal drug treatment |
|
||
NCT04673253
|
Can Passive Leg Raise Prevent Spinal Anesthesia-induced Hypotension During Cesarean Section?
|
All over the world, spinal anesthesia is widely used in cesarean sections due to its superiority over general anesthesia. Due to reasons such as increased sensitivity to local anesthetics and increased intra-abdominal pressure in pregnant women, the frequency of hypotension increases by up to 70%. As a result of the blockage of sympathetic vasoconstrictor fibers originating from T1-L2 segments, loss of peripheral resistance, venous ponding occurs, and cardiac output decreases. Also, the level required for cesarean operation is T4 or T5, and the possibility of affecting the cardiac accelerator fibers, so bradycardia due to the increase in parasympathetic activity may deepen the hypotension. If postspinal hypotension is not managed correctly, it may lead to maternal and fetal complications. In addition to classical methods such as fluid loading and prophylactic vasoconstrictor application to prevent hypotension in pregnant women after spinal anesthesia, techniques such as wrapping the lower extremity, lifting, or applying both together have been in question.~Passive leg raise application is an easy method that allows the blood collected in the lower part of the body to participate in the central circulation with the effect of gravity. An increase in venous return occurs with the passage of blood from the lower extremities to the thorax. Thus, it leads to an increase in stroke volume and an increase in cardiac output. In this study, we aimed to determine the effectiveness of passive leg raising in preventing or reducing the depth of hypotension after spinal anesthesia in pregnant women who underwent cesarean section under spinal anesthesia.
|
Can Passive Leg Raise Prevent Spinal Anesthesia-induced Hypotension During Cesarean Section?
|
Hypotension
|
* Other: Passive leg Raise
* Other: control
|
Inclusion Criteria:~Parturients who are planned for the elective cesarean section~Exclusion Criteria:~Failed spinal block~Shift to general anesthesia~Severe cardiac disease~Hypertensive disorders of pregnancy
|
18 Years
|
40 Years
|
Female
|
No
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systolic blood pressure | Systolic blood pressure will be recorded from the monitor | Before the spinal anesthesia in the supine position |
| Systolic blood pressure | Systolic blood pressure will be recorded from the monitor | 1 minute after the spinal anesthesia in the supine position |
| Systolic blood pressure | Systolic blood pressure will be recorded from the monitor | 2 minutes after the spinal anesthesia in the supine position |
| Systolic blood pressure | Systolic blood pressure will be recorded from the monitor | 3 minutes after the spinal anesthesia in the supine position |
| Systolic blood pressure | Systolic blood pressure will be recorded from the monitor | 4 minutes after the spinal anesthesia in the supine position |
| Systolic blood pressure | Systolic blood pressure will be recorded from the monitor | 5 minutes after the spinal anesthesia in the supine position |
| Systolic blood pressure | Systolic blood pressure will be recorded from the monitor | 7 minutes after the spinal anesthesia in the supine position |
| Systolic blood pressure | Systolic blood pressure will be recorded from the monitor | 9 minutes after the spinal anesthesia in the supine position |
| Systolic blood pressure | Systolic blood pressure will be recorded from the monitor | 11 minutes after the spinal anesthesia in the supine position |
| Systolic blood pressure | Systolic blood pressure will be recorded from the monitor | 1 minute after the umblical cord clamping |
|
cesarean section, hypotension, spinal anesthesia, passive leg raise
|
Hypotension, Vascular Diseases, Cardiovascular Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Passive leg raise<br>group for passive leg raise | Other: Passive leg Raise<br>* The intervention will be performed immediately after spinal anesthesia, and passive leg raise will be performed using two standard pillows placed under the heel so that the leg is approximately 30 cm above the horizontal plane of the table. The passive leg raising position will continue until the cord is clamped.<br>|
| Placebo Comparator: Control<br> | Other: control<br>* The controlled group was positioned in the normal supine position.<br>|
|
Can Passive Leg Raise Prevent Spinal Anesthesia-induced Hypotension During Cesarean Section?
Study Overview
=================
Brief Summary
-----------------
All over the world, spinal anesthesia is widely used in cesarean sections due to its superiority over general anesthesia. Due to reasons such as increased sensitivity to local anesthetics and increased intra-abdominal pressure in pregnant women, the frequency of hypotension increases by up to 70%. As a result of the blockage of sympathetic vasoconstrictor fibers originating from T1-L2 segments, loss of peripheral resistance, venous ponding occurs, and cardiac output decreases. Also, the level required for cesarean operation is T4 or T5, and the possibility of affecting the cardiac accelerator fibers, so bradycardia due to the increase in parasympathetic activity may deepen the hypotension. If postspinal hypotension is not managed correctly, it may lead to maternal and fetal complications. In addition to classical methods such as fluid loading and prophylactic vasoconstrictor application to prevent hypotension in pregnant women after spinal anesthesia, techniques such as wrapping the lower extremity, lifting, or applying both together have been in question. Passive leg raise application is an easy method that allows the blood collected in the lower part of the body to participate in the central circulation with the effect of gravity. An increase in venous return occurs with the passage of blood from the lower extremities to the thorax. Thus, it leads to an increase in stroke volume and an increase in cardiac output. In this study, we aimed to determine the effectiveness of passive leg raising in preventing or reducing the depth of hypotension after spinal anesthesia in pregnant women who underwent cesarean section under spinal anesthesia.
Official Title
-----------------
Can Passive Leg Raise Prevent Spinal Anesthesia-induced Hypotension During Cesarean Section?
Conditions
-----------------
Hypotension
Intervention / Treatment
-----------------
* Other: Passive leg Raise
* Other: control
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Parturients who are planned for the elective cesarean section Exclusion Criteria: Failed spinal block Shift to general anesthesia Severe cardiac disease Hypertensive disorders of pregnancy
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 40 Years
Sexes Eligible for Study
-----------------
Female
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Passive leg raise<br>group for passive leg raise | Other: Passive leg Raise<br>* The intervention will be performed immediately after spinal anesthesia, and passive leg raise will be performed using two standard pillows placed under the heel so that the leg is approximately 30 cm above the horizontal plane of the table. The passive leg raising position will continue until the cord is clamped.<br>|
| Placebo Comparator: Control<br> | Other: control<br>* The controlled group was positioned in the normal supine position.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systolic blood pressure | Systolic blood pressure will be recorded from the monitor | Before the spinal anesthesia in the supine position |
| Systolic blood pressure | Systolic blood pressure will be recorded from the monitor | 1 minute after the spinal anesthesia in the supine position |
| Systolic blood pressure | Systolic blood pressure will be recorded from the monitor | 2 minutes after the spinal anesthesia in the supine position |
| Systolic blood pressure | Systolic blood pressure will be recorded from the monitor | 3 minutes after the spinal anesthesia in the supine position |
| Systolic blood pressure | Systolic blood pressure will be recorded from the monitor | 4 minutes after the spinal anesthesia in the supine position |
| Systolic blood pressure | Systolic blood pressure will be recorded from the monitor | 5 minutes after the spinal anesthesia in the supine position |
| Systolic blood pressure | Systolic blood pressure will be recorded from the monitor | 7 minutes after the spinal anesthesia in the supine position |
| Systolic blood pressure | Systolic blood pressure will be recorded from the monitor | 9 minutes after the spinal anesthesia in the supine position |
| Systolic blood pressure | Systolic blood pressure will be recorded from the monitor | 11 minutes after the spinal anesthesia in the supine position |
| Systolic blood pressure | Systolic blood pressure will be recorded from the monitor | 1 minute after the umblical cord clamping |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
cesarean section, hypotension, spinal anesthesia, passive leg raise
|
||
NCT03373448
|
Treatment of Mild to Moderate Peri-implantitis Using an Oscillating Chitosan Device
|
34 patients diagnosed with mild to moderate peri-implantitis, defined as 2-4 mm peri-implant bone loss, will be randomized to either test treatment with Labrida BioClean® or control treatment with titanium curettes. In total 40 subjects (20 % drop-out rate), treated by 5 clinicians at 5 centers will be included in the study.
|
4.1 Study design The study will be a prospective multicentre randomized, examiner blinded controlled clinical trial of 24 months duration. Change in mucosal inflammation will be reported after 6 months while the true endpoint parameters i.e., peri-implant attachment will be reported after 1 and 2 years.~4.2 Treatment allocation and blinding Patients will be allocated either to test (Labrida BioClean® or control (titanium curettes) treatment by computer-generated block randomization to ensure equal sample sizes. The examiners will be blinded to the treatment allocation.~4.3 Study setting In total six centres will be included. Patient screening, inclusions and all clinical examinations will be performed by a board-certified specialist in periodontology, registered dental hygienist or specialist in prosthetics at each centre. Treatments will be performed by a dental hygienist or a board-certified specialist in periodontology.~4.4 Patients 40 patients (20+20) diagnosed with mild to moderate peri-implantitis, defined as peri-implant bone loss 2 -4 mm, will be included in the study.~4.5 Recruitment of patients~Patients referred to or seeking care in the included clinics will be screened for inclusion.
|
Treatment of Mild to Moderate Peri-implantitis Using an Oscillating Chitosan Device Versus Titanium Curettes - a Multicenter Randomized Clinical Trial
|
Peri-Implantitis
|
* Device: Labrida BioClean
* Other: Titanium curettes
|
Inclusion Criteria:~Peri-implantitis defined as 2-4 mm bone loss distally, mesially or both, Probing Pocket Depth (PPD) ≥4mm and inflammation as demonstrated by Bleeding on Probing (mBoP) at least score 2.~In addition to the above mentioned main inclusion criteria, patients can be included if they meet the following conditions:~Peri-implantitis as defined above on an implant that has been in function for more than 12 months prior to study start.~Above 18 years of age.~Eligible for treatment in an outpatient dental clinic (ie, ASA I and II).~Had full-mouth plaque scores ≤20% prior to final inclusion and no visual plaque at the included implants prior to study start.~Had at least one implant with a loading time of ≥ 12 months prior to baseline.~Signed Informed Consent obtained prior to start.~Psychological appropriateness.~Consent to complete all follow-up visits.~Exclusion Criteria:~Peri-implant bone loss > 4 mm, radiotherapy, chemotherapy, systemic long-term corticosteroid treatment, pregnancy or nursing, anatomical abnormalities, prosthetic factors making access to clinical measurements impossible.~In addition to the above mentioned main exclusion criteria, patients should be excluded if they meet any of the following conditions:~Cemented supraconstructions and/or screw retained supraconstructions that for technical reasons makes it impossible to access implant for clinical measurements.~Technical complications which according to the examiners judgement has contributed to the disease state and not possible to resolve prior to final inclusion.~Mobile implant.~Patients diagnosed with periodontal disease must have undergone causative treatment and be re-evaluated.~Implants previously treated for peri-implantitis with grafting materials.~Receiving medications known to induce mucosal hyperplasia.~Uncontrolled diabetes HbA1c > 52, equals 7.0.~Receiving systemic antibiotics < 3 months prior to inclusion.~Pregnant or lactating.~Any condition or current treatment for any condition, which in the opinion of the investigator and/or consulting physician, may constitute an unwarranted risk.~Presence of psychological characteristics, such as inappropriate attitude or motivation, which will influence treatment execution and treatment outcome.~Unwillingness to undergo treatment.~Advanced, untreated and uncontrolled peri-implantitis on neighbouring implants.~If, in the opinion of the therapist, conditions are such that dental implants are deemed failing.~Ongoing or previous radiotherapy to the head-neck region.~Ongoing or previous chemotherapy.~Systemic long-term corticosteroid treatment.~Patients medicating with warfarine products or similar.~-
|
19 Years
| null |
All
|
No
|
Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be allocated either to test (Labrida BioClean® or control (titanium curettes) treatment by computer-generated block randomization to ensure equal sample sizes. The examiners will be blinded to the treatment allocation.
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammation | Reduction in peri-implant mucositis as measured clinically up to three months after therapy. | 3 months after first treatment |
| Progression of bone loss | True end-point | 12 months after first treatment. |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Morbidity | To compare patient morbidity after use of Labrida BioClean® versus titanium curettes determined on a VAS scale assessed at the 3 month treatment visit. | 3 months |
| Adverse events | To assess safety of BioClean™ by evaluating the occurrence of adverse events. | 12 months |
|
Peri-Implantitis, Periodontal Diseases, Mouth Diseases, Stomatognathic Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Labrida BioClean<br>Labrida BioClean- chitosan device.The brush bristles of the test device (Labrida BioClean® LABRIDA AS, Oslo Norway) are made of the biopolymer chitosan. Any debris left from the chitosan bristles is completely biocompatible and will dissolve or be resorbed thus not causing harm to the tissues surrounding the implant. Chitosan is made from chitin derived from shell of marine crustaceans such as shrimp and crab, however chemically modified and thus not even considered to be animally derived. Chitosan has been approved for use in e.g., surgical bandages, as a haemostatic agent and as dietary supplement used in a wide range of nutritional and health products. Chitosan has also been documented to be non-allergenic and it has been suggested that chitosan has anti-inflammatory properties. | Device: Labrida BioClean<br>* The implant pockets will be debrided with the BioClean™ biodegradable brush for 2 minutes and with the brush seated in an oscillating dental handpiece (NSK ESQ10 TEQ) and thereafter irrigated with sterile saline or commercially available and area-specific titanium curettes (Langer and Langer, Rønvig) for 2 minutes and thereafter irrigated with sterile saline. The treatment will be repeated every three months until the terminal examination after 24 months. Debridement is performed with local anaesthesia as needed. Healthy sites will not be retreated.<br>|
| Other: Titanium curettes<br>Peri-implant pockets will be debrided with titanium curettes. | Other: Titanium curettes<br>* Peri-implant pockets will be debrided using titanium curettes.<br>|
|
Treatment of Mild to Moderate Peri-implantitis Using an Oscillating Chitosan Device
Study Overview
=================
Brief Summary
-----------------
34 patients diagnosed with mild to moderate peri-implantitis, defined as 2-4 mm peri-implant bone loss, will be randomized to either test treatment with Labrida BioClean® or control treatment with titanium curettes. In total 40 subjects (20 % drop-out rate), treated by 5 clinicians at 5 centers will be included in the study.
Detailed Description
-----------------
4.1 Study design The study will be a prospective multicentre randomized, examiner blinded controlled clinical trial of 24 months duration. Change in mucosal inflammation will be reported after 6 months while the true endpoint parameters i.e., peri-implant attachment will be reported after 1 and 2 years. 4.2 Treatment allocation and blinding Patients will be allocated either to test (Labrida BioClean® or control (titanium curettes) treatment by computer-generated block randomization to ensure equal sample sizes. The examiners will be blinded to the treatment allocation. 4.3 Study setting In total six centres will be included. Patient screening, inclusions and all clinical examinations will be performed by a board-certified specialist in periodontology, registered dental hygienist or specialist in prosthetics at each centre. Treatments will be performed by a dental hygienist or a board-certified specialist in periodontology. 4.4 Patients 40 patients (20+20) diagnosed with mild to moderate peri-implantitis, defined as peri-implant bone loss 2 -4 mm, will be included in the study. 4.5 Recruitment of patients Patients referred to or seeking care in the included clinics will be screened for inclusion.
Official Title
-----------------
Treatment of Mild to Moderate Peri-implantitis Using an Oscillating Chitosan Device Versus Titanium Curettes - a Multicenter Randomized Clinical Trial
Conditions
-----------------
Peri-Implantitis
Intervention / Treatment
-----------------
* Device: Labrida BioClean
* Other: Titanium curettes
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Peri-implantitis defined as 2-4 mm bone loss distally, mesially or both, Probing Pocket Depth (PPD) ≥4mm and inflammation as demonstrated by Bleeding on Probing (mBoP) at least score 2. In addition to the above mentioned main inclusion criteria, patients can be included if they meet the following conditions: Peri-implantitis as defined above on an implant that has been in function for more than 12 months prior to study start. Above 18 years of age. Eligible for treatment in an outpatient dental clinic (ie, ASA I and II). Had full-mouth plaque scores ≤20% prior to final inclusion and no visual plaque at the included implants prior to study start. Had at least one implant with a loading time of ≥ 12 months prior to baseline. Signed Informed Consent obtained prior to start. Psychological appropriateness. Consent to complete all follow-up visits. Exclusion Criteria: Peri-implant bone loss > 4 mm, radiotherapy, chemotherapy, systemic long-term corticosteroid treatment, pregnancy or nursing, anatomical abnormalities, prosthetic factors making access to clinical measurements impossible. In addition to the above mentioned main exclusion criteria, patients should be excluded if they meet any of the following conditions: Cemented supraconstructions and/or screw retained supraconstructions that for technical reasons makes it impossible to access implant for clinical measurements. Technical complications which according to the examiners judgement has contributed to the disease state and not possible to resolve prior to final inclusion. Mobile implant. Patients diagnosed with periodontal disease must have undergone causative treatment and be re-evaluated. Implants previously treated for peri-implantitis with grafting materials. Receiving medications known to induce mucosal hyperplasia. Uncontrolled diabetes HbA1c > 52, equals 7.0. Receiving systemic antibiotics < 3 months prior to inclusion. Pregnant or lactating. Any condition or current treatment for any condition, which in the opinion of the investigator and/or consulting physician, may constitute an unwarranted risk. Presence of psychological characteristics, such as inappropriate attitude or motivation, which will influence treatment execution and treatment outcome. Unwillingness to undergo treatment. Advanced, untreated and uncontrolled peri-implantitis on neighbouring implants. If, in the opinion of the therapist, conditions are such that dental implants are deemed failing. Ongoing or previous radiotherapy to the head-neck region. Ongoing or previous chemotherapy. Systemic long-term corticosteroid treatment. Patients medicating with warfarine products or similar. -
Ages Eligible for Study
-----------------
Minimum Age: 19 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be allocated either to test (Labrida BioClean® or control (titanium curettes) treatment by computer-generated block randomization to ensure equal sample sizes. The examiners will be blinded to the treatment allocation.
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Labrida BioClean<br>Labrida BioClean- chitosan device.The brush bristles of the test device (Labrida BioClean® LABRIDA AS, Oslo Norway) are made of the biopolymer chitosan. Any debris left from the chitosan bristles is completely biocompatible and will dissolve or be resorbed thus not causing harm to the tissues surrounding the implant. Chitosan is made from chitin derived from shell of marine crustaceans such as shrimp and crab, however chemically modified and thus not even considered to be animally derived. Chitosan has been approved for use in e.g., surgical bandages, as a haemostatic agent and as dietary supplement used in a wide range of nutritional and health products. Chitosan has also been documented to be non-allergenic and it has been suggested that chitosan has anti-inflammatory properties. | Device: Labrida BioClean<br>* The implant pockets will be debrided with the BioClean™ biodegradable brush for 2 minutes and with the brush seated in an oscillating dental handpiece (NSK ESQ10 TEQ) and thereafter irrigated with sterile saline or commercially available and area-specific titanium curettes (Langer and Langer, Rønvig) for 2 minutes and thereafter irrigated with sterile saline. The treatment will be repeated every three months until the terminal examination after 24 months. Debridement is performed with local anaesthesia as needed. Healthy sites will not be retreated.<br>|
| Other: Titanium curettes<br>Peri-implant pockets will be debrided with titanium curettes. | Other: Titanium curettes<br>* Peri-implant pockets will be debrided using titanium curettes.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammation | Reduction in peri-implant mucositis as measured clinically up to three months after therapy. | 3 months after first treatment |
| Progression of bone loss | True end-point | 12 months after first treatment. |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Morbidity | To compare patient morbidity after use of Labrida BioClean® versus titanium curettes determined on a VAS scale assessed at the 3 month treatment visit. | 3 months |
| Adverse events | To assess safety of BioClean™ by evaluating the occurrence of adverse events. | 12 months |
|
|
NCT03858777
|
Cell Free DNA in Cardiac Sarcoidosis
|
Sarcoidosis is a multisystem granulomatous disease of unknown cause that can affect any organ in the body, including the heart. Granulomatous myocarditis can lead to ventricular dysfunction and ventricular arrhythmias causing significant morbidity and mortality. Immunosuppressive therapy (IST) has been shown to reverse active myocarditis and preserve left ventricular (LV) function and in some cases improve LV function. In addition, IST can suppress arrhythmias that develop due to active myocarditis and prevent the formation of scar.~The potential role of cardiac biomarkers, including brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), and cardiac troponins, in detecting active myocarditis is limited and studies have been disappointing. At present, there are no biomarkers to detect active myocarditis and the use of advanced imaging modalities (FDG-PET) for assessing and monitoring active myocarditis is not feasible or practical and is associate with high radiation exposure. As such, a biomarker that is reflective of active myocarditis and that is cardiac specific will assist physicians in assessing the presence of active myocarditis to guide therapeutic decisions and to assess response to therapy which can limit further cardiac damage.~Cell free DNA (cfDNA) are fragments of genomic DNA that are released into the circulation from dying or damaged cells. It is a powerful diagnostic tool in cancer, transplant rejection and fetal medicine especially when the genomic source differs from the host. A novel technique that relies on tissue unique CpG methylation patterns can identify the tissue source of cell free DNA in an individual reflecting potential tissue injury. We will be conducting a pilot study to explore the utility of this diagnostic tool to identify granulomatous myocarditis in patients with sarcoidosis.
|
Sarcoidosis is a multisystem granulomatous disease of unknown cause that can affect any organ in the body, including the heart. Sarcoidosis results from an immune reaction to an environmental exposure to yet unknown antigen(s) in a genetically predisposed individual. Autopsy studies have suggested that cardiac involvement with sarcoidosis occurs in up to 25% of cases, although more than half of these cases are sub-clinical. Cardiac sarcoidosis (CS) CS can lead to life-threatening heart failure, heart block, or rhythm disturbance and accounts for 13-25% of all sarcoidosis deaths in the USA. Therefore, although respiratory failure from lung sarcoidosis is the most common cause of sarcoidosis-related death in the USA, sudden death from cardiac sarcoidosis is a major concern owing to its acute nature. CS can present in a multitude of ways. It can be the initial manifestation of sarcoidosis in an individual not known to have sarcoidosis (a cohort beyond the aims of this proposal), patients can present with cardiac symptoms which can include palpitations, near-syncope or syncopal episodes which require a complete workup for potential CS and patients can be asymptomatic which is a sizable cohort considering the discrepancy between the expected prevalence of CS (25-40%) and CS that is detected clinically (5%).~Granulomatous myocarditis can lead to ventricular dysfunction and ventricular arrhythmias causing significant morbidity and mortality. Immunosuppressive therapy (IST) has been shown to reverse active myocarditis and preserve left ventricular (LV) function and in some cases improve LV function. In addition, IST can suppress arrhythmias that develop due to active myocarditis and prevent the formation of scar. Cardiac MRI (cMRI) and cardiac PET scans are currently used as complementary diagnostic tests for cardiac sarcoidosis, although with some limitations. Cardiac MRI with gadolinium has a sensitivity of 76-100% and specificity of 78-92% for the diagnosis of cardiac sarcoidosis, but its use is limited in patients with implantable cardiac devices. The presence of delayed enhancement on gadolinium-enhanced MRI is suggestive of scar tissue formation. 18FDG PET uses radioactive glucose to detect areas of active inflammation. The use of 18FDG PET as a marker of active granulomatous myocarditis should be interpreted carefully as several studies have shown the limitations of such protocols that force the myocardium to generate energy using free fatty acid metabolism exclusively. In addition, studies have also shown that the presumed pathological patterns, focal and focal on diffuse uptake, are also seen in healthy controls and patients with ischemic congestive heart failure who have undergone 18-FDG-PET12 and that a blood glucose level of >7.5mmol/L (>137mg/dl) at the time of the study results in absent or minimal myocardial FDG activity.~The potential role of cardiac biomarkers, including brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), and cardiac troponins, in detecting active myocarditis is limited and studies have been disappointing. At present, there are no biomarkers to detect active myocarditis and the use of advanced imaging modalities (FDG-PET) for assessing and monitoring active myocarditis is not feasible or practical and is associate with high radiation exposure. As such, a biomarker that is reflective of active myocarditis and that is cardiac specific will assist physicians in assessing the presence of active myocarditis to guide therapeutic decisions and to assess response to therapy which can limit further cardiac damage.~Cell free DNA (cfDNA) are fragments of genomic DNA that are released into the circulation from dying or damaged cells. It is a powerful diagnostic tool in cancer, transplant rejection and fetal medicine especially when the genomic source differs from the host. A novel technique that relies on tissue unique CpG methylation patterns can identify the tissue source of cell free DNA in an individual reflecting potential tissue injury. A recent paper utilized this technique to identify cardiac specific cfDNA in the bloodstream of patients with acute myocardial injury and sepsis reflecting cardiomyocyte injury/death. We will be conducting a pilot study to explore the utility of this diagnostic tool to identify granulomatous myocarditis in patients with sarcoidosis.
|
Cardiomyocyte Specific Cell Free DNA as a Marker of Cardiac Sarcoidosis
|
Sarcoidosis With Myocarditis, Sarcoidosis, Healthy, ST Elevation Myocardial Infarction
|
* Diagnostic Test: cell free DNA
|
Sarcoidosis patients without evidence of active myocarditis:~Inclusion:~Diagnosis of sarcoidosis based on the ATS/ERS criteria.~Normal 12 lead ECG within the past one year.~Non-smoker.~No immunosuppressive therapy for at least one year.~Exclusion:~Known cardiac disease.~Active smoker.~On immunosuppressive therapy.~Sarcoidosis patients with evidence of active myocarditis:~Inclusion:~Diagnosis of sarcoidosis based on the ATS/ERS criteria.~Evidence of active myocarditis based on recent cMRI or cFDG-PET.~Non-smoker.~Exclusion:~Known cardiac disease other than sarcoidosis.~Active smoker.~On immunosuppressive therapy.~Acute ST elevation myocardial infarction (STEMI):~Inclusion:~Diagnosis STEMI based on 1mm ST elevation in 2 or more contiguous leads.~Symptom onset within 12 hours.~Undergoing cardiac intervention for acute coronary syndrome.~Able to consent for blood draw.~Exclusion:~Active smoker.~Hemodynamically unstable.~Healthy controls:~Inclusion:~No known cardiac disease.~No known cardiovascular risk factors: hypertension, diabetes.~Non-smoker.
|
18 Years
| null |
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cfDNA level | cfDNA level | cfDNA level at baseline and 2 months for sarcoidosis with heart disease compared to cfDNA levels at baseline for healthy controls and sarcoidosis without cardiac disease and cfDNA levels at baseline, 6 and 24 hours for STEMI patients. |
|
sarcoidosis
|
Myocarditis, Myocardial Infarction, ST Elevation Myocardial Infarction, Sarcoidosis, Infarction, Ischemia, Pathologic Processes, Necrosis, Myocardial Ischemia, Heart Diseases, Cardiovascular Diseases, Vascular Diseases, Lymphoproliferative Disorders, Lymphatic Diseases, Hypersensitivity, Delayed, Hypersensitivity, Immune System Diseases, Cardiomyopathies
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sarcoidosis patients without evidence of active myocarditis<br>A single blood draw. | Diagnostic Test: cell free DNA<br>* All groups will have blood draws and cfDNA measured<br>|
| Experimental: Sarcoidosis patients with evidence of active myocarditis<br>Two blood draws 2 months apart. | Diagnostic Test: cell free DNA<br>* All groups will have blood draws and cfDNA measured<br>|
| Active Comparator: Acute ST elevation myocardial infarction (STEMI)<br>Three blood draws, baseline, 6 hours and 24 hours. | Diagnostic Test: cell free DNA<br>* All groups will have blood draws and cfDNA measured<br>|
| Placebo Comparator: Healthy controls<br>A single blood draw | Diagnostic Test: cell free DNA<br>* All groups will have blood draws and cfDNA measured<br>|
|
Cell Free DNA in Cardiac Sarcoidosis
Study Overview
=================
Brief Summary
-----------------
Sarcoidosis is a multisystem granulomatous disease of unknown cause that can affect any organ in the body, including the heart. Granulomatous myocarditis can lead to ventricular dysfunction and ventricular arrhythmias causing significant morbidity and mortality. Immunosuppressive therapy (IST) has been shown to reverse active myocarditis and preserve left ventricular (LV) function and in some cases improve LV function. In addition, IST can suppress arrhythmias that develop due to active myocarditis and prevent the formation of scar. The potential role of cardiac biomarkers, including brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), and cardiac troponins, in detecting active myocarditis is limited and studies have been disappointing. At present, there are no biomarkers to detect active myocarditis and the use of advanced imaging modalities (FDG-PET) for assessing and monitoring active myocarditis is not feasible or practical and is associate with high radiation exposure. As such, a biomarker that is reflective of active myocarditis and that is cardiac specific will assist physicians in assessing the presence of active myocarditis to guide therapeutic decisions and to assess response to therapy which can limit further cardiac damage. Cell free DNA (cfDNA) are fragments of genomic DNA that are released into the circulation from dying or damaged cells. It is a powerful diagnostic tool in cancer, transplant rejection and fetal medicine especially when the genomic source differs from the host. A novel technique that relies on tissue unique CpG methylation patterns can identify the tissue source of cell free DNA in an individual reflecting potential tissue injury. We will be conducting a pilot study to explore the utility of this diagnostic tool to identify granulomatous myocarditis in patients with sarcoidosis.
Detailed Description
-----------------
Sarcoidosis is a multisystem granulomatous disease of unknown cause that can affect any organ in the body, including the heart. Sarcoidosis results from an immune reaction to an environmental exposure to yet unknown antigen(s) in a genetically predisposed individual. Autopsy studies have suggested that cardiac involvement with sarcoidosis occurs in up to 25% of cases, although more than half of these cases are sub-clinical. Cardiac sarcoidosis (CS) CS can lead to life-threatening heart failure, heart block, or rhythm disturbance and accounts for 13-25% of all sarcoidosis deaths in the USA. Therefore, although respiratory failure from lung sarcoidosis is the most common cause of sarcoidosis-related death in the USA, sudden death from cardiac sarcoidosis is a major concern owing to its acute nature. CS can present in a multitude of ways. It can be the initial manifestation of sarcoidosis in an individual not known to have sarcoidosis (a cohort beyond the aims of this proposal), patients can present with cardiac symptoms which can include palpitations, near-syncope or syncopal episodes which require a complete workup for potential CS and patients can be asymptomatic which is a sizable cohort considering the discrepancy between the expected prevalence of CS (25-40%) and CS that is detected clinically (5%). Granulomatous myocarditis can lead to ventricular dysfunction and ventricular arrhythmias causing significant morbidity and mortality. Immunosuppressive therapy (IST) has been shown to reverse active myocarditis and preserve left ventricular (LV) function and in some cases improve LV function. In addition, IST can suppress arrhythmias that develop due to active myocarditis and prevent the formation of scar. Cardiac MRI (cMRI) and cardiac PET scans are currently used as complementary diagnostic tests for cardiac sarcoidosis, although with some limitations. Cardiac MRI with gadolinium has a sensitivity of 76-100% and specificity of 78-92% for the diagnosis of cardiac sarcoidosis, but its use is limited in patients with implantable cardiac devices. The presence of delayed enhancement on gadolinium-enhanced MRI is suggestive of scar tissue formation. 18FDG PET uses radioactive glucose to detect areas of active inflammation. The use of 18FDG PET as a marker of active granulomatous myocarditis should be interpreted carefully as several studies have shown the limitations of such protocols that force the myocardium to generate energy using free fatty acid metabolism exclusively. In addition, studies have also shown that the presumed pathological patterns, focal and focal on diffuse uptake, are also seen in healthy controls and patients with ischemic congestive heart failure who have undergone 18-FDG-PET12 and that a blood glucose level of >7.5mmol/L (>137mg/dl) at the time of the study results in absent or minimal myocardial FDG activity. The potential role of cardiac biomarkers, including brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), and cardiac troponins, in detecting active myocarditis is limited and studies have been disappointing. At present, there are no biomarkers to detect active myocarditis and the use of advanced imaging modalities (FDG-PET) for assessing and monitoring active myocarditis is not feasible or practical and is associate with high radiation exposure. As such, a biomarker that is reflective of active myocarditis and that is cardiac specific will assist physicians in assessing the presence of active myocarditis to guide therapeutic decisions and to assess response to therapy which can limit further cardiac damage. Cell free DNA (cfDNA) are fragments of genomic DNA that are released into the circulation from dying or damaged cells. It is a powerful diagnostic tool in cancer, transplant rejection and fetal medicine especially when the genomic source differs from the host. A novel technique that relies on tissue unique CpG methylation patterns can identify the tissue source of cell free DNA in an individual reflecting potential tissue injury. A recent paper utilized this technique to identify cardiac specific cfDNA in the bloodstream of patients with acute myocardial injury and sepsis reflecting cardiomyocyte injury/death. We will be conducting a pilot study to explore the utility of this diagnostic tool to identify granulomatous myocarditis in patients with sarcoidosis.
Official Title
-----------------
Cardiomyocyte Specific Cell Free DNA as a Marker of Cardiac Sarcoidosis
Conditions
-----------------
Sarcoidosis With Myocarditis, Sarcoidosis, Healthy, ST Elevation Myocardial Infarction
Intervention / Treatment
-----------------
* Diagnostic Test: cell free DNA
Participation Criteria
=================
Eligibility Criteria
-----------------
Sarcoidosis patients without evidence of active myocarditis: Inclusion: Diagnosis of sarcoidosis based on the ATS/ERS criteria. Normal 12 lead ECG within the past one year. Non-smoker. No immunosuppressive therapy for at least one year. Exclusion: Known cardiac disease. Active smoker. On immunosuppressive therapy. Sarcoidosis patients with evidence of active myocarditis: Inclusion: Diagnosis of sarcoidosis based on the ATS/ERS criteria. Evidence of active myocarditis based on recent cMRI or cFDG-PET. Non-smoker. Exclusion: Known cardiac disease other than sarcoidosis. Active smoker. On immunosuppressive therapy. Acute ST elevation myocardial infarction (STEMI): Inclusion: Diagnosis STEMI based on 1mm ST elevation in 2 or more contiguous leads. Symptom onset within 12 hours. Undergoing cardiac intervention for acute coronary syndrome. Able to consent for blood draw. Exclusion: Active smoker. Hemodynamically unstable. Healthy controls: Inclusion: No known cardiac disease. No known cardiovascular risk factors: hypertension, diabetes. Non-smoker.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sarcoidosis patients without evidence of active myocarditis<br>A single blood draw. | Diagnostic Test: cell free DNA<br>* All groups will have blood draws and cfDNA measured<br>|
| Experimental: Sarcoidosis patients with evidence of active myocarditis<br>Two blood draws 2 months apart. | Diagnostic Test: cell free DNA<br>* All groups will have blood draws and cfDNA measured<br>|
| Active Comparator: Acute ST elevation myocardial infarction (STEMI)<br>Three blood draws, baseline, 6 hours and 24 hours. | Diagnostic Test: cell free DNA<br>* All groups will have blood draws and cfDNA measured<br>|
| Placebo Comparator: Healthy controls<br>A single blood draw | Diagnostic Test: cell free DNA<br>* All groups will have blood draws and cfDNA measured<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cfDNA level | cfDNA level | cfDNA level at baseline and 2 months for sarcoidosis with heart disease compared to cfDNA levels at baseline for healthy controls and sarcoidosis without cardiac disease and cfDNA levels at baseline, 6 and 24 hours for STEMI patients. |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
sarcoidosis
|
|
NCT02581319
|
Clinical Conditions and Prevalence of Periodontopathogens in Smokers and Non-smokers After Periodontal Therapy
|
Smoking has been considered the most important risk factor for periodontitis among all lifestyle factors. Fewer studies evaluated longitudinal clinical and microbiological status of smokers undergoing periodontal maintenance therapy and controversial results were found. This study will evaluate clinical conditions and prevalence of putative periodontopathogens and Candida spp. in smokers and non-smokers at baseline and after 3 and 6 months of nonsurgical periodontal therapy. Clinical parameters, including oral status assessed using Plaque Index (PI), Bleeding On Probe (BOP), Pocket Probing Depth (PPD), Gingival Recession (GR), Clinical Attachment Level (CAL) will be measured in smokers and non-smokers patients with chronic periodontitis. Samples of subgingival biofilm will be obtained from the periodontal pockets and furcation sites and submitted to phenol-chloroform DNA extraction and Polymerase Chain Reaction (PCR) analysis using specific primers for Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Prevotella intermedia, Campylobacter rectus, Candida albicans, Candida glabrata, Candida tropicalis and Candida dublinienses.
|
Sixty patients (30 smokers (SM) and 30 non-smokers (NS) will be selected to participate of this study. All subjects will be recruited from the Department of Periodontology, School of Dentistry, Fluminense Federal University, Nova Friburgo, Rio de Janeiro State, Brazil. The study protocol was approved (protocol number: CAAE - 0070.0.258.000-10) by the Ethics Committee of the School of Medicine, Fluminense Federal University. Prior to participation, the purpose and procedures will be fully explained to all patients, who consequently gave written informed consent in accordance with the Helsinki Declaration. Medical and dental histories will be taken and patients will receive clinical evaluation at prescreening visits.~Clinical examination, microbiological collects and periodontal therapy Previous clinical examination, information about years of consumption of cigars and quantity of daily consumption will be recorded to select smokers and non- smokers subjects for the study. An experienced periodontist will perform clinical periodontal parameters in teeth for the protocol procedure. Each selected tooth selected will be measured for: Plaque Index (PI), Bleeding On Probe (BOP), Pocket Probing Depth (PPD), Gingival Recession (GR), Clinical Attachment Level (CAL) using a periodontal probe PCP15 (PCP-UNC15, Hu-Friedy, Chicago, IL), six sites (mesio-buccal, mediobuccal, disto-buccal, mesio-lingual, medio-lingual, disto-lingual) will be recorded. Sites with probing depth (PPD) > 5mm will be selected for microbiological analysis. After clinical measurements, the supragingival biofilm will be removed with sterile gauze. Gingival crevicular samples will be taken from 4 sites with the deepest PPD (>5mm) in each patient using a sterile paper point from the deepest pocket for 30s. Pooled biofilms from each site will be separated in two microtubes containing Tris -EDTA buffer (10 mM Tris-Hcl, 0.1 mM EDTA, pH 7.5) and were stored at -20°C. The samples will be analyzed microbiologically by Polymerase Chain Reaction - PCR. Periodontal treatment will be consisted of scaling and planning root, 4 times in first month and after that once a month until complete 1 year. Patients will be clinically evaluated and microbiological collects will be made at baseline, 3 months, 6 months and 1 year after periodontal treatment.~Microbiological evaluation - PCR assays DNA will be extracted and quantified in a spectrophotometer at 260 nm (Genesys 10UV, Rochester, NY, USA), in order to obtain a standard concentration of 100 ng/mL and stored at -20 °C for subsequent PCR reactions. Briefly, samples will be submitted to a lise solution (extraction buffer and proteinase K) and then purified using chloroform:isoamil-alcohol, followed by DNA precipitation with isopropanol and 70% ethanol. The DNA will be resuspended in TE buffer (10 mM Tris-HCl, 0.1 mM EDTA, pH 7.5, with 10 μg/mL RNAse). Microbial molecular identification will be carried out by PCR with specific primers for Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Prevotella intermedia, Campylobacter rectus, Candida albicans, Candida glabrata, Candida tropicalis and Candida dublinienses. PCR amplification will be performed with a GeneAmp PCR system 2400 (Perkin-Elmer - Applied Biosystems) for TGradient 96 (Biometra, Germany) under thermal conditions specific for each pair of primers. The PCR products will be separated by electrophoresis in 2% agarose gels and Tris-borate-EDTA running buffer (pH 8.0). The molecular mass ladder (100 bp DNA ladder, Gibco, Grand Island, NY, USA) will be included for running in the agarose gel. The DNA will be stained with 0.1µl of Sybr Safe/mL (Invitrogen, CA, USA) and visualized under UV illumination (Pharmacia LKB-MacroVue, San Gabriel, CA, USA). Photographs of the images will be taken (Image Mater - LISCAP, VDS, Pharmacia Biotech Piscataway, NJ, USA) and analyzed.
|
Clinical Conditions and Prevalence of Periodontopathogens in Smokers and Non-smokers After Periodontal Therapy
|
Periodontal Disease, Smoking
|
* Procedure: Periodontal treatment
|
Inclusion Criteria:~presence of periodontal disease in unirradicular teeth~bleeding on probing in sites where probing depth was ≥5 mm in a minimum of two teeth in different arch;~radiographic bone loss ranging from 30% to 50%.~Exclusion Criteria:~patients with systemic diseases, diabetes; osteoporosis;~pregnant lactating females;~use of immune suppressive medication, phenytoin, cyclosporine, calcium channel blockers or any use of antibiotics or nonsteroidal anti-inflammatory drugs in the past 3 months;~any medical conditions requiring immunotherapy or diagnosed as HIV+ or with AIDS, that could interfere with the periodontium status.
|
18 Years
|
70 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of periodontal status represented by means/standard deviations of the percentage of high scores of PI and BOP and levels (mm) of PPD, GR and CAL in smokers and non-smokers patients before and after periodontal treatment | An experienced periodontist will perform clinical periodontal analysis and periodontal treatment. Six sites (mesio-buccal, mediobuccal, disto-buccal, mesio-lingual, medio-lingual, disto-lingual) of each selected tooth (at least six teeth) will be measured using standard scores for the following periodontal markers: Plaque Index (PI) and Bleeding On Probe (BOP) and determined the levels (mm) of Pocket Probing Depth (PPD), Gingival Recession (GR) and Clinical Attachment Level (CAL) using a periodontal probe PCP15 (PCP-UNC15, Hu-Friedy, Chicago, IL). Means/standard deviations will be calculated from the percentage of high scores of PI and BOP and levels (mm) of PPD, GR and CAL for each patient and after that for each group: smokers and non-smokers. All patients with periodontal disease (high scores of periodontal markers) will be submitted to periodontal treatment and clinically evaluated at baseline, 3 months, 6 months and 1 year after treatment. | Up to one year |
| Prevalence of periodontopathogens calculated in percentage of sites containing the species tested for PCR, comparing smokers and non-smokers | Gingival crevicular samples will be taken from 4 sites with the deepest PPD (>5mm) in each patient. DNA from these samples will be extracted using phenol-chloroform method and quantified in a spectrophotometer at 260 nm and stored at -20 °C. Microbial molecular identification will be carried out by PCR with specific primers for Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Prevotella intermedia, Campylobacter rectus, Candida albicans, Candida glabrata, Candida tropicalis and Candida dublinienses. PCR amplification will be performed with a GeneAmp PCR system 2400 (Perkin-Elmer - Applied Biosystems) for TGradient 96 (Biometra, Germany) under thermal conditions specific for each pair of primers. The prevalence of periodontopathogens will be calculated in percentage of sites containing the species tested for PCR, comparing smokers and non-smokers at baseline, 3 months, 6 months and 1 year after periodontal treatment. | Up to one year |
|
Periodontal Diseases, Mouth Diseases, Stomatognathic Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Periodontal treatment<br>Both groups of patients (smokers and non-smokers) will receive periodontal treatment consisting of scaling and planning root, 4 times in the first month and after that once a month until complete one year. Patients will be clinically evaluated and microbiological collects will be made at baseline, 3 months, 6 months and 1 year after periodontal treatment. | Procedure: Periodontal treatment<br>* Periodontal treatment will consist of scaling and planning root, 4 times in the first month and after that once a month until complete one year. Patients will be clinically evaluated and microbiological collects were made at baseline, 3 months, 6 months and 1 year after periodontal treatment.<br>* Other names: Scaling and planning root;|
|
Clinical Conditions and Prevalence of Periodontopathogens in Smokers and Non-smokers After Periodontal Therapy
Study Overview
=================
Brief Summary
-----------------
Smoking has been considered the most important risk factor for periodontitis among all lifestyle factors. Fewer studies evaluated longitudinal clinical and microbiological status of smokers undergoing periodontal maintenance therapy and controversial results were found. This study will evaluate clinical conditions and prevalence of putative periodontopathogens and Candida spp. in smokers and non-smokers at baseline and after 3 and 6 months of nonsurgical periodontal therapy. Clinical parameters, including oral status assessed using Plaque Index (PI), Bleeding On Probe (BOP), Pocket Probing Depth (PPD), Gingival Recession (GR), Clinical Attachment Level (CAL) will be measured in smokers and non-smokers patients with chronic periodontitis. Samples of subgingival biofilm will be obtained from the periodontal pockets and furcation sites and submitted to phenol-chloroform DNA extraction and Polymerase Chain Reaction (PCR) analysis using specific primers for Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Prevotella intermedia, Campylobacter rectus, Candida albicans, Candida glabrata, Candida tropicalis and Candida dublinienses.
Detailed Description
-----------------
Sixty patients (30 smokers (SM) and 30 non-smokers (NS) will be selected to participate of this study. All subjects will be recruited from the Department of Periodontology, School of Dentistry, Fluminense Federal University, Nova Friburgo, Rio de Janeiro State, Brazil. The study protocol was approved (protocol number: CAAE - 0070.0.258.000-10) by the Ethics Committee of the School of Medicine, Fluminense Federal University. Prior to participation, the purpose and procedures will be fully explained to all patients, who consequently gave written informed consent in accordance with the Helsinki Declaration. Medical and dental histories will be taken and patients will receive clinical evaluation at prescreening visits. Clinical examination, microbiological collects and periodontal therapy Previous clinical examination, information about years of consumption of cigars and quantity of daily consumption will be recorded to select smokers and non- smokers subjects for the study. An experienced periodontist will perform clinical periodontal parameters in teeth for the protocol procedure. Each selected tooth selected will be measured for: Plaque Index (PI), Bleeding On Probe (BOP), Pocket Probing Depth (PPD), Gingival Recession (GR), Clinical Attachment Level (CAL) using a periodontal probe PCP15 (PCP-UNC15, Hu-Friedy, Chicago, IL), six sites (mesio-buccal, mediobuccal, disto-buccal, mesio-lingual, medio-lingual, disto-lingual) will be recorded. Sites with probing depth (PPD) > 5mm will be selected for microbiological analysis. After clinical measurements, the supragingival biofilm will be removed with sterile gauze. Gingival crevicular samples will be taken from 4 sites with the deepest PPD (>5mm) in each patient using a sterile paper point from the deepest pocket for 30s. Pooled biofilms from each site will be separated in two microtubes containing Tris -EDTA buffer (10 mM Tris-Hcl, 0.1 mM EDTA, pH 7.5) and were stored at -20°C. The samples will be analyzed microbiologically by Polymerase Chain Reaction - PCR. Periodontal treatment will be consisted of scaling and planning root, 4 times in first month and after that once a month until complete 1 year. Patients will be clinically evaluated and microbiological collects will be made at baseline, 3 months, 6 months and 1 year after periodontal treatment. Microbiological evaluation - PCR assays DNA will be extracted and quantified in a spectrophotometer at 260 nm (Genesys 10UV, Rochester, NY, USA), in order to obtain a standard concentration of 100 ng/mL and stored at -20 °C for subsequent PCR reactions. Briefly, samples will be submitted to a lise solution (extraction buffer and proteinase K) and then purified using chloroform:isoamil-alcohol, followed by DNA precipitation with isopropanol and 70% ethanol. The DNA will be resuspended in TE buffer (10 mM Tris-HCl, 0.1 mM EDTA, pH 7.5, with 10 μg/mL RNAse). Microbial molecular identification will be carried out by PCR with specific primers for Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Prevotella intermedia, Campylobacter rectus, Candida albicans, Candida glabrata, Candida tropicalis and Candida dublinienses. PCR amplification will be performed with a GeneAmp PCR system 2400 (Perkin-Elmer - Applied Biosystems) for TGradient 96 (Biometra, Germany) under thermal conditions specific for each pair of primers. The PCR products will be separated by electrophoresis in 2% agarose gels and Tris-borate-EDTA running buffer (pH 8.0). The molecular mass ladder (100 bp DNA ladder, Gibco, Grand Island, NY, USA) will be included for running in the agarose gel. The DNA will be stained with 0.1µl of Sybr Safe/mL (Invitrogen, CA, USA) and visualized under UV illumination (Pharmacia LKB-MacroVue, San Gabriel, CA, USA). Photographs of the images will be taken (Image Mater - LISCAP, VDS, Pharmacia Biotech Piscataway, NJ, USA) and analyzed.
Official Title
-----------------
Clinical Conditions and Prevalence of Periodontopathogens in Smokers and Non-smokers After Periodontal Therapy
Conditions
-----------------
Periodontal Disease, Smoking
Intervention / Treatment
-----------------
* Procedure: Periodontal treatment
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: presence of periodontal disease in unirradicular teeth bleeding on probing in sites where probing depth was ≥5 mm in a minimum of two teeth in different arch; radiographic bone loss ranging from 30% to 50%. Exclusion Criteria: patients with systemic diseases, diabetes; osteoporosis; pregnant lactating females; use of immune suppressive medication, phenytoin, cyclosporine, calcium channel blockers or any use of antibiotics or nonsteroidal anti-inflammatory drugs in the past 3 months; any medical conditions requiring immunotherapy or diagnosed as HIV+ or with AIDS, that could interfere with the periodontium status.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Periodontal treatment<br>Both groups of patients (smokers and non-smokers) will receive periodontal treatment consisting of scaling and planning root, 4 times in the first month and after that once a month until complete one year. Patients will be clinically evaluated and microbiological collects will be made at baseline, 3 months, 6 months and 1 year after periodontal treatment. | Procedure: Periodontal treatment<br>* Periodontal treatment will consist of scaling and planning root, 4 times in the first month and after that once a month until complete one year. Patients will be clinically evaluated and microbiological collects were made at baseline, 3 months, 6 months and 1 year after periodontal treatment.<br>* Other names: Scaling and planning root;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of periodontal status represented by means/standard deviations of the percentage of high scores of PI and BOP and levels (mm) of PPD, GR and CAL in smokers and non-smokers patients before and after periodontal treatment | An experienced periodontist will perform clinical periodontal analysis and periodontal treatment. Six sites (mesio-buccal, mediobuccal, disto-buccal, mesio-lingual, medio-lingual, disto-lingual) of each selected tooth (at least six teeth) will be measured using standard scores for the following periodontal markers: Plaque Index (PI) and Bleeding On Probe (BOP) and determined the levels (mm) of Pocket Probing Depth (PPD), Gingival Recession (GR) and Clinical Attachment Level (CAL) using a periodontal probe PCP15 (PCP-UNC15, Hu-Friedy, Chicago, IL). Means/standard deviations will be calculated from the percentage of high scores of PI and BOP and levels (mm) of PPD, GR and CAL for each patient and after that for each group: smokers and non-smokers. All patients with periodontal disease (high scores of periodontal markers) will be submitted to periodontal treatment and clinically evaluated at baseline, 3 months, 6 months and 1 year after treatment. | Up to one year |
| Prevalence of periodontopathogens calculated in percentage of sites containing the species tested for PCR, comparing smokers and non-smokers | Gingival crevicular samples will be taken from 4 sites with the deepest PPD (>5mm) in each patient. DNA from these samples will be extracted using phenol-chloroform method and quantified in a spectrophotometer at 260 nm and stored at -20 °C. Microbial molecular identification will be carried out by PCR with specific primers for Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Prevotella intermedia, Campylobacter rectus, Candida albicans, Candida glabrata, Candida tropicalis and Candida dublinienses. PCR amplification will be performed with a GeneAmp PCR system 2400 (Perkin-Elmer - Applied Biosystems) for TGradient 96 (Biometra, Germany) under thermal conditions specific for each pair of primers. The prevalence of periodontopathogens will be calculated in percentage of sites containing the species tested for PCR, comparing smokers and non-smokers at baseline, 3 months, 6 months and 1 year after periodontal treatment. | Up to one year |
|
||
NCT04727346
|
Evaluation of Post-surgical Improvement in OSA Patients After Imaging of Upper Airway Using CBCT and DISE vs DISE Only
|
CBCT is considered an innovative imaging modality that can view the upper respiratory airway anatomy in a 3D manner. Recent studies tried to evaluate the accuracy of CBCT in analyzing the upper respiratory airway and its related structures. Although, most of these studies aimed to evaluate the 3D imaging of upper respiratory airway in OSA patients and their healthy counterparts, the determination of its level of collapse with the aid of CBCT wasn't clearly evaluated.~DISE is considered a dynamic approach to determine the level of upper respiratory airway collapse accurately, but CBCT can offer better evaluation of anatomical upper respiratory airway characteristics and morphology which in turn affects treatment planning and patients' satisfaction after surgery. The hypothesis is agreed with other studies who found that retroglossal collapse appears more frequently during the end of expiration imaged by dynamic MRI.~Our hypothesis is the validity of CBCT in determining the level of collapse through assessing different orthogonal planes at end of inspiration and expiration especially in those patients having a tongue/palate interaction or lengthy palate where this anatomical variation wasn't been probably evaluated with DISE.
|
In this validity two-arm study, a total (n) patients will be included; all are diagnosed with OSA and will undergo surgical treatment after appropriate planning. Patients will be classified into two equal groups with allocation ratio (1:1). Patients of the study group will be examined after scanning with CBCT at both ends of expiration and inspiration and DISE. Control group patients will be examined by DISE only. After discussing the treatment plan with the patient and educating the patient with all the data needed, an arabic consent form will be signed by the willing participants.~These (n) patients will be selected by the ENT specialist according to the following;~A multidisciplinary approach will be performed to diagnose OSA patients who are indicated for surgery. Firstly, a comprehensive assessment of patients' history will be performed; including evaluation of all risk factors and complete sleep history.~Epworth Sleepiness Scale (ESS) which consists of eight section questionnaire that defines the frequency of an individual to fall asleep during regular daily activities will be obtained from the patients.~Afterward, a proper physical examination will be performed including a thorough clinical examination of the oropharynx, nasopharynx, and hypopharynx to evaluate any anatomical abnormalities as impotency of the nasal airway, elongated soft palate or uvula, enlarged lingual tonsils, and any other pathological conditions of tongue, palate, and tonsils.~Then, Polysomnography (PSG) (sleep study) will be performed to allow proper evaluation of normal and abnormal physiological sleep episodes. Apnea/Hypoapnea Index (AHI) will be reported to detect the severity of OSA and patients were classified into mild (AHI = 5-14/ hour), moderate (AHI = 15-30 / hour) and severe (AHI >30 / hour).~All patients in both groups will undergo upper airway surgery, DISE will be performed by the same ENT surgeon to detect the level of collapse in the upper airway which will be assessed by LwPTL and VOTE classifications, emphasizing on the primary structures contributing at upper airway collapse, either alone or in combination: the larynx, palate, tongue and pharyngeal lateral walls.~Study group participants only will be scanned by CBCT twice; once at the end of inspiration and the other at the end of expiration while they are gently holding their breath for as long as possible.~In the study group, surgical procedures decision will be taken after appropriate assessment to sites of collapse in CBCT views at both ends of expiration and inspiration vies in combination to DISE.~Finally, strict post-operative instructions will be given to patients of both group and a 3 months follow up would be done.
|
Assessment of Post-surgical Improvement in Obstructive Sleep Apnea Patients After Imaging of Upper Respiratory Airway Using Cone Beam Computed Tomography (CBCT) and Drug-Induced Sleep Endoscopy (DISE) Versus Drug-Induced Sleep Endoscopy Only: A Validity Study
|
Obstructive Sleep Apnea
|
* Radiation: CBCT
* Procedure: DISE
|
Inclusion Criteria:~Patients' age is more than 18 years old.~Patients are indicated for upper respiratory airway surgery based on adequate history taking, proper clinical examination, and sleep study.~Patients refusing Continuous Positive Airway Pressure (CPAP) treatment.~Systemically medically free patients.~Exclusion Criteria:~Patients who are refusing the surgical approach as a treatment plan option.~Patients who have undergone previous surgeries in the upper respiratory airway.~Pregnant women.~Patients who didn't follow post-operative instructions.~Patients who are not able to come for the follow-up appointments.
|
18 Years
| null |
All
|
Accepts Healthy Volunteers
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-surgical improvement | through Mean Apnea/Hypoapnea Index (AHI) reduction percentage by Polysomnography (PSG) (sleep study) | 3 months after the surgery |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Level of Collapse of the upper respiratory airway | through LwPTL Classification | immediately after performing both DISE and CBCT |
| The volume of the upper respiratory airway. | through CBCT images (Invivo5 software) | through study completion, an average of 1 year |
|
CBCT, OSA, DISE
|
Dyssomnias, Sleep Apnea Syndromes, Sleep Apnea, Obstructive, Apnea, Respiration Disorders, Respiratory Tract Diseases, Sleep Disorders, Intrinsic, Sleep Wake Disorders, Nervous System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Study Group<br>CBCT and DISE | Radiation: CBCT<br>* Cone Beam Computed Tomography<br>Procedure: DISE<br>* Drug Induced Sleep Endoscopy<br>|
| Control Group<br>DISE only | Procedure: DISE<br>* Drug Induced Sleep Endoscopy<br>|
|
Evaluation of Post-surgical Improvement in OSA Patients After Imaging of Upper Airway Using CBCT and DISE vs DISE Only
Study Overview
=================
Brief Summary
-----------------
CBCT is considered an innovative imaging modality that can view the upper respiratory airway anatomy in a 3D manner. Recent studies tried to evaluate the accuracy of CBCT in analyzing the upper respiratory airway and its related structures. Although, most of these studies aimed to evaluate the 3D imaging of upper respiratory airway in OSA patients and their healthy counterparts, the determination of its level of collapse with the aid of CBCT wasn't clearly evaluated. DISE is considered a dynamic approach to determine the level of upper respiratory airway collapse accurately, but CBCT can offer better evaluation of anatomical upper respiratory airway characteristics and morphology which in turn affects treatment planning and patients' satisfaction after surgery. The hypothesis is agreed with other studies who found that retroglossal collapse appears more frequently during the end of expiration imaged by dynamic MRI. Our hypothesis is the validity of CBCT in determining the level of collapse through assessing different orthogonal planes at end of inspiration and expiration especially in those patients having a tongue/palate interaction or lengthy palate where this anatomical variation wasn't been probably evaluated with DISE.
Detailed Description
-----------------
In this validity two-arm study, a total (n) patients will be included; all are diagnosed with OSA and will undergo surgical treatment after appropriate planning. Patients will be classified into two equal groups with allocation ratio (1:1). Patients of the study group will be examined after scanning with CBCT at both ends of expiration and inspiration and DISE. Control group patients will be examined by DISE only. After discussing the treatment plan with the patient and educating the patient with all the data needed, an arabic consent form will be signed by the willing participants. These (n) patients will be selected by the ENT specialist according to the following; A multidisciplinary approach will be performed to diagnose OSA patients who are indicated for surgery. Firstly, a comprehensive assessment of patients' history will be performed; including evaluation of all risk factors and complete sleep history. Epworth Sleepiness Scale (ESS) which consists of eight section questionnaire that defines the frequency of an individual to fall asleep during regular daily activities will be obtained from the patients. Afterward, a proper physical examination will be performed including a thorough clinical examination of the oropharynx, nasopharynx, and hypopharynx to evaluate any anatomical abnormalities as impotency of the nasal airway, elongated soft palate or uvula, enlarged lingual tonsils, and any other pathological conditions of tongue, palate, and tonsils. Then, Polysomnography (PSG) (sleep study) will be performed to allow proper evaluation of normal and abnormal physiological sleep episodes. Apnea/Hypoapnea Index (AHI) will be reported to detect the severity of OSA and patients were classified into mild (AHI = 5-14/ hour), moderate (AHI = 15-30 / hour) and severe (AHI >30 / hour). All patients in both groups will undergo upper airway surgery, DISE will be performed by the same ENT surgeon to detect the level of collapse in the upper airway which will be assessed by LwPTL and VOTE classifications, emphasizing on the primary structures contributing at upper airway collapse, either alone or in combination: the larynx, palate, tongue and pharyngeal lateral walls. Study group participants only will be scanned by CBCT twice; once at the end of inspiration and the other at the end of expiration while they are gently holding their breath for as long as possible. In the study group, surgical procedures decision will be taken after appropriate assessment to sites of collapse in CBCT views at both ends of expiration and inspiration vies in combination to DISE. Finally, strict post-operative instructions will be given to patients of both group and a 3 months follow up would be done.
Official Title
-----------------
Assessment of Post-surgical Improvement in Obstructive Sleep Apnea Patients After Imaging of Upper Respiratory Airway Using Cone Beam Computed Tomography (CBCT) and Drug-Induced Sleep Endoscopy (DISE) Versus Drug-Induced Sleep Endoscopy Only: A Validity Study
Conditions
-----------------
Obstructive Sleep Apnea
Intervention / Treatment
-----------------
* Radiation: CBCT
* Procedure: DISE
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients' age is more than 18 years old. Patients are indicated for upper respiratory airway surgery based on adequate history taking, proper clinical examination, and sleep study. Patients refusing Continuous Positive Airway Pressure (CPAP) treatment. Systemically medically free patients. Exclusion Criteria: Patients who are refusing the surgical approach as a treatment plan option. Patients who have undergone previous surgeries in the upper respiratory airway. Pregnant women. Patients who didn't follow post-operative instructions. Patients who are not able to come for the follow-up appointments.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Study Group<br>CBCT and DISE | Radiation: CBCT<br>* Cone Beam Computed Tomography<br>Procedure: DISE<br>* Drug Induced Sleep Endoscopy<br>|
| Control Group<br>DISE only | Procedure: DISE<br>* Drug Induced Sleep Endoscopy<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-surgical improvement | through Mean Apnea/Hypoapnea Index (AHI) reduction percentage by Polysomnography (PSG) (sleep study) | 3 months after the surgery |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Level of Collapse of the upper respiratory airway | through LwPTL Classification | immediately after performing both DISE and CBCT |
| The volume of the upper respiratory airway. | through CBCT images (Invivo5 software) | through study completion, an average of 1 year |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CBCT, OSA, DISE
|
|
NCT03091218
|
Surveillance for Early Liver Injuries Caused by Runzao Zhiyang Capsule.
|
This is a prospective registry study to surveil early liver injuries caused by Runzao Zhiyang Capsule (RZZY Capsule) through a non-intervention observational way. And attempt to establish a predictive model to screen susceptibilities to RZZY Capsule.
|
The primary objectives of this study include:~(i) The detection of patients with serum liver biochemistry abnormalities less than 8 weeks after intake of RZZY Capsule; (ii) The record of overall individuals with demographics, underlying diseases, physical status, medication information, clinical laboratory index, and so on; (iii) The specimen collection of surveiled individuals. (iv) The attempt to establish a predictive model to screen susceptibilities to RZZY Capsule.
|
A Registry Study to Surveil Early Liver Injuries Caused by Runzao Zhiyang Capsule (RZZY Capsule).
|
Drug-Induced Liver Injury
|
Inclusion Criteria:~Individuals in accordance with indications for RZZY Capsule, including skin pruritus, acne vulgaris and constipation;~The age range of 18 to 70 years；~Individuals taking RZZY Capsule over 2 weeks;~Abnormalities of serum biochemistry achieving one of the criteria as follows:~(i) alanine aminotransaminase (ALT) or aspartate transaminase (AST) ≥2 folds of upper limit of normal (ULN); (ii) total bilirubin (TBiL) ≥ 2 ULN; (iii) alkaline phosphatase (ALP) ≥ 2 ULN;~Individuals can provide informed consent form.~Exclusion Criteria:~Individuals without indications for RZZY Capsule;~Unconformity with the RZZY Capsule drug label;~Individual taking RZZY Capsule less than 2 weeks;~Individuals taking other hepatotoxic drugs combined with RZZY Capsule, simultaneously;~Unconformity with the diagnostic standard for herb-induced liver injury (the Guideline for Diagnosis and Treatment of Herb-induced Liver Injury, RPGIP-2016CN003）.
|
18 Years
|
70 Years
|
All
|
Accepts Healthy Volunteers
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The detection of patients with serum liver biochemistry abnormalities within 8 weeks after intake of RZZY Capsule. | The detection of patients with serum liver biochemistry abnormalities within 8 weeks after intake of RZZY Capsule. | participants will be followed duration intake of RZZY Capsule, an expected average within 8 weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical features of early liver injuries caused by RZZY Capsule assessed by serum parameters of liver function. | Clinical features of early liver injuries caused by RZZY Capsule assessed by serum parameters of liver function. | participants will be followed duration intake of RZZY Capsule, an expected average of 8 weeks |
|
Drug-Induced Liver Injury
|
Chemical and Drug Induced Liver Injury, Wounds and Injuries, Liver Diseases, Digestive System Diseases, Drug-Related Side Effects and Adverse Reactions, Chemically-Induced Disorders, Poisoning
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| The individuals taking RZZY Capsule<br>The overall individuals taking RZZY Capsule with recommended dosage and achieving the inclusion criteria. | |
|
Surveillance for Early Liver Injuries Caused by Runzao Zhiyang Capsule.
Study Overview
=================
Brief Summary
-----------------
This is a prospective registry study to surveil early liver injuries caused by Runzao Zhiyang Capsule (RZZY Capsule) through a non-intervention observational way. And attempt to establish a predictive model to screen susceptibilities to RZZY Capsule.
Detailed Description
-----------------
The primary objectives of this study include: (i) The detection of patients with serum liver biochemistry abnormalities less than 8 weeks after intake of RZZY Capsule; (ii) The record of overall individuals with demographics, underlying diseases, physical status, medication information, clinical laboratory index, and so on; (iii) The specimen collection of surveiled individuals. (iv) The attempt to establish a predictive model to screen susceptibilities to RZZY Capsule.
Official Title
-----------------
A Registry Study to Surveil Early Liver Injuries Caused by Runzao Zhiyang Capsule (RZZY Capsule).
Conditions
-----------------
Drug-Induced Liver Injury
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Individuals in accordance with indications for RZZY Capsule, including skin pruritus, acne vulgaris and constipation; The age range of 18 to 70 years； Individuals taking RZZY Capsule over 2 weeks; Abnormalities of serum biochemistry achieving one of the criteria as follows: (i) alanine aminotransaminase (ALT) or aspartate transaminase (AST) ≥2 folds of upper limit of normal (ULN); (ii) total bilirubin (TBiL) ≥ 2 ULN; (iii) alkaline phosphatase (ALP) ≥ 2 ULN; Individuals can provide informed consent form. Exclusion Criteria: Individuals without indications for RZZY Capsule; Unconformity with the RZZY Capsule drug label; Individual taking RZZY Capsule less than 2 weeks; Individuals taking other hepatotoxic drugs combined with RZZY Capsule, simultaneously; Unconformity with the diagnostic standard for herb-induced liver injury (the Guideline for Diagnosis and Treatment of Herb-induced Liver Injury, RPGIP-2016CN003）.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| The individuals taking RZZY Capsule<br>The overall individuals taking RZZY Capsule with recommended dosage and achieving the inclusion criteria. | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The detection of patients with serum liver biochemistry abnormalities within 8 weeks after intake of RZZY Capsule. | The detection of patients with serum liver biochemistry abnormalities within 8 weeks after intake of RZZY Capsule. | participants will be followed duration intake of RZZY Capsule, an expected average within 8 weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical features of early liver injuries caused by RZZY Capsule assessed by serum parameters of liver function. | Clinical features of early liver injuries caused by RZZY Capsule assessed by serum parameters of liver function. | participants will be followed duration intake of RZZY Capsule, an expected average of 8 weeks |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Drug-Induced Liver Injury
|
||
NCT05647642
|
The Effect of Premedication on Postoperative Pain and Anxiety in Breast Cancer Surgery
|
In this study, it was investigated whether the premedication drug administered before the surgery had an effect on postoperative pain and anxiety scores in female patients under the age of 65 who will undergo breast cancer surgery.
|
In this study, it was investigated whether the premedication drug administered before the surgery had an effect on postoperative pain and anxiety scores in female patients under the age of 65 who will undergo breast cancer surgery. The STAI-1(State Trait Anxiety İnventory ) form and APAIS (Amsterdam Preoperative Anxiety and İnformation Scale) scale were filled in for all preoperative patients. Afterwards, the patients were treated with either midazolam or dexmedetothymidine, depending on the anesthesiologist's preference. After administration, he was taken to surgery. As intraoperative analgesics, 2 mg/kg tramadol and 15 mg/kg paracetamol were administered to all patients. postoperative recovery time (aldrete 10), 1., 2.,6.,12.,24. VAS score, postoperative nausea-vomiting scale, STAI-1(State Trait Anxiety İnventory ) form, first need time if postoperative analgesic was needed, and 24-hour total analgesic consumption were recorded. It was aimed to examine the effects of different premedications on postoperative pain and anxiety
|
The Effect of Premedication Methods to be Applied to Prevent Preoperative Anxiety in Patients Who Will be Operated for Breast Cancer, on Postoperative Anxiety and Pain
|
Female Patients Under the Age of 65 Who Will Undergo Breast Cancer Surgery
|
* Drug: Precedex and dormicum
|
Inclusion Criteria:~ASA 1-2-3~18-65 aged~Female patients~Exclusion Criteria:~Under 18 years old and over 65 years old~Having a history of cerebrovascular disease illiteracy~Have visual and auditory problems İnability to cooperate with cognitive function test~Having emergency surgery~Those who are unable to read, understand and sign the consent form~Patients deemed unsuitable by the investigator
|
18 Years
|
65 Years
|
Female
|
Accepts Healthy Volunteers
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| effect of premedication on postoperative pain and anxiety scores | | November 2022-December 2022 |
|
Anesthetics, Midazolam, Dexmedetomidine, Hypnotics and Sedatives, Central Nervous System Depressants, Physiological Effects of Drugs, Analgesics, Non-Narcotic, Analgesics, Sensory System Agents, Peripheral Nervous System Agents, Adrenergic alpha-2 Receptor Agonists, Adrenergic alpha-Agonists, Adrenergic Agonists, Adrenergic Agents, Neurotransmitter Agents, Molecular Mechanisms of Pharmacological Action, Adjuvants, Anesthesia, Anti-Anxiety Agents, Tranquilizing Agents, Psychotropic Drugs, Anesthetics, Intravenous, Anesthetics, General, GABA Modulators, GABA Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| low dose midazolam<br>0,025 mg/kg Midazolam | Drug: Precedex and dormicum<br>* Premedication<br>|
| high dose midazolam<br>0,05 mg/kg Midazolam | Drug: Precedex and dormicum<br>* Premedication<br>|
| low dose dexmedetothymidine<br>0.5 mg/kg dexmedetothymidine 10 minute infusion | Drug: Precedex and dormicum<br>* Premedication<br>|
| high dose dexmedetothymidine<br>1mg/kg dexmedetothymidine 10 minute infusion | Drug: Precedex and dormicum<br>* Premedication<br>|
|
The Effect of Premedication on Postoperative Pain and Anxiety in Breast Cancer Surgery
Study Overview
=================
Brief Summary
-----------------
In this study, it was investigated whether the premedication drug administered before the surgery had an effect on postoperative pain and anxiety scores in female patients under the age of 65 who will undergo breast cancer surgery.
Detailed Description
-----------------
In this study, it was investigated whether the premedication drug administered before the surgery had an effect on postoperative pain and anxiety scores in female patients under the age of 65 who will undergo breast cancer surgery. The STAI-1(State Trait Anxiety İnventory ) form and APAIS (Amsterdam Preoperative Anxiety and İnformation Scale) scale were filled in for all preoperative patients. Afterwards, the patients were treated with either midazolam or dexmedetothymidine, depending on the anesthesiologist's preference. After administration, he was taken to surgery. As intraoperative analgesics, 2 mg/kg tramadol and 15 mg/kg paracetamol were administered to all patients. postoperative recovery time (aldrete 10), 1., 2.,6.,12.,24. VAS score, postoperative nausea-vomiting scale, STAI-1(State Trait Anxiety İnventory ) form, first need time if postoperative analgesic was needed, and 24-hour total analgesic consumption were recorded. It was aimed to examine the effects of different premedications on postoperative pain and anxiety
Official Title
-----------------
The Effect of Premedication Methods to be Applied to Prevent Preoperative Anxiety in Patients Who Will be Operated for Breast Cancer, on Postoperative Anxiety and Pain
Conditions
-----------------
Female Patients Under the Age of 65 Who Will Undergo Breast Cancer Surgery
Intervention / Treatment
-----------------
* Drug: Precedex and dormicum
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: ASA 1-2-3 18-65 aged Female patients Exclusion Criteria: Under 18 years old and over 65 years old Having a history of cerebrovascular disease illiteracy Have visual and auditory problems İnability to cooperate with cognitive function test Having emergency surgery Those who are unable to read, understand and sign the consent form Patients deemed unsuitable by the investigator
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years
Sexes Eligible for Study
-----------------
Female
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| low dose midazolam<br>0,025 mg/kg Midazolam | Drug: Precedex and dormicum<br>* Premedication<br>|
| high dose midazolam<br>0,05 mg/kg Midazolam | Drug: Precedex and dormicum<br>* Premedication<br>|
| low dose dexmedetothymidine<br>0.5 mg/kg dexmedetothymidine 10 minute infusion | Drug: Precedex and dormicum<br>* Premedication<br>|
| high dose dexmedetothymidine<br>1mg/kg dexmedetothymidine 10 minute infusion | Drug: Precedex and dormicum<br>* Premedication<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| effect of premedication on postoperative pain and anxiety scores | | November 2022-December 2022 |
|
|||
NCT03459235
|
Assessment of Functional Digestive and Genitourinary Outcomes in Patients With Rectal Cancer.
|
Total mesorectal excision and neoadjuvant radio-chemotherapy have revolutionized the management of rectal cancer allowing an increase in survival (between 55 and 68% at 5 years) and allowing a decrease of local recurrence (under 10%) and allowing to push the limits of sphinctyer saving procedures.~Parallel to the oncological findings, evaluating quality of life and functionnals sequelae has become a priority as highlighted by the second axis of plan cancer 2014-2019.~The prevalence of digestive functional sequelae decrease during the first two years after surgery. However, these results are difficult to analyse due to the heterogeneity of used scores in medical litterature. The low anterior resection syndrom associate poly-exoneration, gas and / or stool incontinence, urgency and stool splitting.~The score of low anterior resection LARS score validated in Danemark in 2012 allow us to understand the complexity of these sequelae and to measure their impact on the quality of life of patients, that's why he is currently recommended.~In the long term, almost two out of three patients suffer from this syndrom, with half of the patients in a severe form.~However, its prevalence and severity are often underestimated by practitioners. It leads to inappropriate therapeutic measures. The aim of this study is to evaluate the impact of digestive and genito-urinary sequelae on quality of life from validated scores in patients operated curatively of rectal cancer using a population study.~This study should include 676 patients with rectal cancer treated in calvados and alive at 2 years of their proctectomy without local or general recurrence.
|
Assessment of Functional Digestive and Genitourinary Outcomes in Patients With Rectal Cancer Living After 2 Years Without Recurrence. Population Study. (Rectqol)
|
Rectal Cancer, Surgery
|
* Other: quality of life
|
Inclusion Criteria:~Patients operated for a rectal adénocarcinoma with a curative aim with or without neo-adjuvating treatment in Calvados between January 1st, 2007 (date of recommendations for clinical practise) and december 31 th, 2014.~Patients having their main address in the Calvados (at the time of diagnosis) and recorded in the register of digestive tumors of the Calvados.~patients alive on first of january 2018 without local recurrence nor global recurrence~patients able to understant a validated questionnaire.~Exclusion Criteria:~Dead patients~patients with cancer recurrence~Patient with severe cognitive disorders (confusions) preventing the good understanding of questionnaires.
|
18 Years
|
80 Years
|
All
|
No
|
Primary Purpose: Screening
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| assessment of digestive sequelae in patients operated for a rectal cancer (rectal resection) | score used : LARS score (for men and women). 5 questions about the low anterior resection syndrom. Scale between 0 and 42 points. Better outcome is 0 and worse is 42. | more than 2 years after rectal resection |
| assessment of global quality of life in patients operated for a rectal cancer (rectal resection) | Score used : EORTC - QLQ C-30 - European Organization for research and treatment of cancer Quality of Life Questionnaire Core 30 (for men and women). It is a scale to evaluate the generic quality of life after cancer. There are 30 questions : 28 questions with 4 possible answers from 1 to 4 and 2 questions to evaluate the physical state and global quality of life with answers between 1 and 7. For each answer, 1 is the worst outcome and 4 is the best except for the 2 last questions where 7 is the best outcome. Minimum (worst outcome) is 30 and best outcome is 126. The total is reported to a score of 100 points which is the best outcome. | more than 2 years after rectal resection |
| assessment of specific quality of life in patients operated for a rectal cancer (rectal resection) | score used : EORTC - QLQ CR 29 European Organization for research and treatment of cancer Quality of Life Questionnaire Colorecatl module 29 (for men and women). This score is used in patients undergoing treatment for colorectal cancer. There are 29 questions with 4 possible answers (between 1 and 4 points). Best outcome is 4 for each question. Worst outcome is 1 for each question. Minimum (worst outcome) is 29 and best outcome is 116. The total is reported to a score of 100 points which is the best outcome. | more than 2 years after rectal resection |
| assessment of quality of life of patients operated for a rectal cancer (rectal resection) - urinary sequelae (for women) | score used : Urinary Symptom Profile : USP (for women). This scale is used to evaluate urinary symptoms. 1 question to evaluate stress urinary incontinence (between 0 and 9 points). 9 points is the worts outcome. 7 questions to evaluate overactive bladder symtoms (between 0 points and 21). 21 points is the worst outcome. 3 questions to evaluate low stream symtoms (between 0 and 9 points). 9 points is the worst outcome.~Global score is between 0 and 39 points. 39 points is the worst outcome and 0 points the best outcome. | more than 2 years after rectal resection |
| assessment of quality of life of patients operated for a rectal cancer (rectal resection) - urinary sequelae (for men) | score used : International Prostate Score Symptom : IPSS (for men). There are 7 questions with 5 possible answers (between 0 (best outcome) and 5 (worst outcome)). And one additionnal question to evaluate quality of life due to urinary symptom with 7 possible answers from 0 (best outcome) to 6 (worst outcome). for the seven first questions : best outcome is 0 and worst outcome is 35. For the last question 0 is the best and 6 is the worst outcome). | more than 2 years after rectal resection |
| assessment of quality of life of patients operated for a rectal cancer (rectal resection) - Sexual sequelae (for women) | score used : Female Sexual Functionnal index : FSFI (for women). 19 questions on sexual sequelae in this questionnaire. Worst outcome is 2 and best outcome is 95 points. | more than 2 years after rectal resection |
| assessment of quality of life of patients operated for a rectal cancer (rectal resection) - Sexual sequelae (for men) | score used : International Index for Erectile Function 5 : IIEF 5 (for men). 5 questions for sexual quality of life in males. Each questions have 5 answers. 5 points is the best outcome for each question. Minimal score is 1 and best score (best outcome) is 25. | more than 2 years after rectal resection |
|
rectal cancer, proctectomy, digestive sequelae, quality of life, Urinary and Sexual sequelae
|
Rectal Neoplasms, Colorectal Neoplasms, Intestinal Neoplasms, Gastrointestinal Neoplasms, Digestive System Neoplasms, Neoplasms by Site, Neoplasms, Digestive System Diseases, Gastrointestinal Diseases, Intestinal Diseases, Rectal Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: population from registry data<br>the intervention involves completing several quality of life questionnaires validated in the medical literature (LARS score, FSFI, USP, IIEF, IPPS, QLQ C-30, QLQ-CR29) | Other: quality of life<br>* Assessment of the impact of digestive sequelae (LARS score) and genitourinary sequelae (score IPSS, USP, FSFI et IIEF) in Patients With Rectal Cancer using validated questionnaires on quality of life (EORTC QLQ-C30 et QLQ-CR 29).<br>|
|
Assessment of Functional Digestive and Genitourinary Outcomes in Patients With Rectal Cancer.
Study Overview
=================
Brief Summary
-----------------
Total mesorectal excision and neoadjuvant radio-chemotherapy have revolutionized the management of rectal cancer allowing an increase in survival (between 55 and 68% at 5 years) and allowing a decrease of local recurrence (under 10%) and allowing to push the limits of sphinctyer saving procedures. Parallel to the oncological findings, evaluating quality of life and functionnals sequelae has become a priority as highlighted by the second axis of plan cancer 2014-2019. The prevalence of digestive functional sequelae decrease during the first two years after surgery. However, these results are difficult to analyse due to the heterogeneity of used scores in medical litterature. The low anterior resection syndrom associate poly-exoneration, gas and / or stool incontinence, urgency and stool splitting. The score of low anterior resection LARS score validated in Danemark in 2012 allow us to understand the complexity of these sequelae and to measure their impact on the quality of life of patients, that's why he is currently recommended. In the long term, almost two out of three patients suffer from this syndrom, with half of the patients in a severe form. However, its prevalence and severity are often underestimated by practitioners. It leads to inappropriate therapeutic measures. The aim of this study is to evaluate the impact of digestive and genito-urinary sequelae on quality of life from validated scores in patients operated curatively of rectal cancer using a population study. This study should include 676 patients with rectal cancer treated in calvados and alive at 2 years of their proctectomy without local or general recurrence.
Official Title
-----------------
Assessment of Functional Digestive and Genitourinary Outcomes in Patients With Rectal Cancer Living After 2 Years Without Recurrence. Population Study. (Rectqol)
Conditions
-----------------
Rectal Cancer, Surgery
Intervention / Treatment
-----------------
* Other: quality of life
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients operated for a rectal adénocarcinoma with a curative aim with or without neo-adjuvating treatment in Calvados between January 1st, 2007 (date of recommendations for clinical practise) and december 31 th, 2014. Patients having their main address in the Calvados (at the time of diagnosis) and recorded in the register of digestive tumors of the Calvados. patients alive on first of january 2018 without local recurrence nor global recurrence patients able to understant a validated questionnaire. Exclusion Criteria: Dead patients patients with cancer recurrence Patient with severe cognitive disorders (confusions) preventing the good understanding of questionnaires.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Screening
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: population from registry data<br>the intervention involves completing several quality of life questionnaires validated in the medical literature (LARS score, FSFI, USP, IIEF, IPPS, QLQ C-30, QLQ-CR29) | Other: quality of life<br>* Assessment of the impact of digestive sequelae (LARS score) and genitourinary sequelae (score IPSS, USP, FSFI et IIEF) in Patients With Rectal Cancer using validated questionnaires on quality of life (EORTC QLQ-C30 et QLQ-CR 29).<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| assessment of digestive sequelae in patients operated for a rectal cancer (rectal resection) | score used : LARS score (for men and women). 5 questions about the low anterior resection syndrom. Scale between 0 and 42 points. Better outcome is 0 and worse is 42. | more than 2 years after rectal resection |
| assessment of global quality of life in patients operated for a rectal cancer (rectal resection) | Score used : EORTC - QLQ C-30 - European Organization for research and treatment of cancer Quality of Life Questionnaire Core 30 (for men and women). It is a scale to evaluate the generic quality of life after cancer. There are 30 questions : 28 questions with 4 possible answers from 1 to 4 and 2 questions to evaluate the physical state and global quality of life with answers between 1 and 7. For each answer, 1 is the worst outcome and 4 is the best except for the 2 last questions where 7 is the best outcome. Minimum (worst outcome) is 30 and best outcome is 126. The total is reported to a score of 100 points which is the best outcome. | more than 2 years after rectal resection |
| assessment of specific quality of life in patients operated for a rectal cancer (rectal resection) | score used : EORTC - QLQ CR 29 European Organization for research and treatment of cancer Quality of Life Questionnaire Colorecatl module 29 (for men and women). This score is used in patients undergoing treatment for colorectal cancer. There are 29 questions with 4 possible answers (between 1 and 4 points). Best outcome is 4 for each question. Worst outcome is 1 for each question. Minimum (worst outcome) is 29 and best outcome is 116. The total is reported to a score of 100 points which is the best outcome. | more than 2 years after rectal resection |
| assessment of quality of life of patients operated for a rectal cancer (rectal resection) - urinary sequelae (for women) | score used : Urinary Symptom Profile : USP (for women). This scale is used to evaluate urinary symptoms. 1 question to evaluate stress urinary incontinence (between 0 and 9 points). 9 points is the worts outcome. 7 questions to evaluate overactive bladder symtoms (between 0 points and 21). 21 points is the worst outcome. 3 questions to evaluate low stream symtoms (between 0 and 9 points). 9 points is the worst outcome. Global score is between 0 and 39 points. 39 points is the worst outcome and 0 points the best outcome. | more than 2 years after rectal resection |
| assessment of quality of life of patients operated for a rectal cancer (rectal resection) - urinary sequelae (for men) | score used : International Prostate Score Symptom : IPSS (for men). There are 7 questions with 5 possible answers (between 0 (best outcome) and 5 (worst outcome)). And one additionnal question to evaluate quality of life due to urinary symptom with 7 possible answers from 0 (best outcome) to 6 (worst outcome). for the seven first questions : best outcome is 0 and worst outcome is 35. For the last question 0 is the best and 6 is the worst outcome). | more than 2 years after rectal resection |
| assessment of quality of life of patients operated for a rectal cancer (rectal resection) - Sexual sequelae (for women) | score used : Female Sexual Functionnal index : FSFI (for women). 19 questions on sexual sequelae in this questionnaire. Worst outcome is 2 and best outcome is 95 points. | more than 2 years after rectal resection |
| assessment of quality of life of patients operated for a rectal cancer (rectal resection) - Sexual sequelae (for men) | score used : International Index for Erectile Function 5 : IIEF 5 (for men). 5 questions for sexual quality of life in males. Each questions have 5 answers. 5 points is the best outcome for each question. Minimal score is 1 and best score (best outcome) is 25. | more than 2 years after rectal resection |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
rectal cancer, proctectomy, digestive sequelae, quality of life, Urinary and Sexual sequelae
|
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