<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04422223</url>
  </required_header>
  <id_info>
    <org_study_id>H-19024348</org_study_id>
    <nct_id>NCT04422223</nct_id>
  </id_info>
  <brief_title>Prospective Cohort Study of Disease and Outcomes in Cirrhosis</brief_title>
  <acronym>ProDoc</acronym>
  <official_title>Copenhagen Liver Cohort Study: Disease Characteristics, Outcomes and Rehabilitation in Liver Cirrhosis - A Prospective Cohort Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Copenhagen University Hospital, Hvidovre</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Copenhagen</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Copenhagen University Hospital, Hvidovre</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A population based incidence cohort will enroll patients newly diagnosed with cirrhosis to&#xD;
      investigate disease characteristics and outcomes, explore mechanisms predicting early death&#xD;
      and hospital admission, and assess new monitoring tools in treatment and prevention of&#xD;
      cirrhosis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      INTRODUCTION In Denmark the incidence of liver cirrhosis is increasing. From 1996 to 2005 the&#xD;
      number of hospital admissions due to liver cirrhosis rose with 2,500 extra admissions per&#xD;
      year. Patients who are readmitted to the hospital have a higher 90 days mortality than those&#xD;
      who avoid readmission.&#xD;
&#xD;
      Liver cirrhosis in Denmark is caused by a wide use of alcohol and a population increasing in&#xD;
      age and BMI.&#xD;
&#xD;
      The course of cirrhosis depends on etiology, age and nutritional status, as well as social&#xD;
      factors such as personal network, employment and economy. Interventional studies on many of&#xD;
      these mechanisms are still unexplored.&#xD;
&#xD;
      Cirrhosis is related to decreased quality of life and affects patients and relatives both&#xD;
      emotional and socioeconomically.&#xD;
&#xD;
      The Gastro Unit, Amager Hvidovre Hospital has a catchment area of 550,000 citizens in South&#xD;
      and West of Copenhagen. The Gastro Unit diagnoses app. 140 people with liver cirrhosis&#xD;
      yearly.&#xD;
&#xD;
      Patient education and rehabilitation is implemented as standard health care after significant&#xD;
      pulmonary or cardiac disease in all regions of Denmark.&#xD;
&#xD;
      HYPOTHESIS A systematic approach to investigation, treatment and rehabilitation in liver&#xD;
      cirrhosis will improve the patient's ability to benefit from medical treatment and health&#xD;
      care offers and increase patient involvement and autonomy in disease.&#xD;
&#xD;
      A systematic approach to investigation of liver disease will contribute to identify new risk&#xD;
      factors for death, hospital admission and readmission, and decompensation in liver cirrhosis.&#xD;
&#xD;
      Better knowledge on sociodemographic features, use of health care resources and the patient's&#xD;
      physical performance and frailty will improve new actions of personalized treatment,&#xD;
      interventions focusing on patient needs and patient reported outcomes in cirrhosis.&#xD;
&#xD;
      Primary outcome The primary aim for this prospective cohort study is to improve&#xD;
      characterization, treatment and rehabilitation under and after admission of patients with&#xD;
      liver cirrhosis, with the purpose of improving survival and reducing risk of readmission.&#xD;
&#xD;
      Secondary outcomes&#xD;
&#xD;
        -  To identify 'frail patients' and to improve their access to health care offers.&#xD;
&#xD;
        -  To improve the utilization of health care resources by a systematic approach to patient&#xD;
           characterization and treatment.&#xD;
&#xD;
        -  To identify co-factors with importance for early death and readmission.&#xD;
&#xD;
        -  To identify and explore new targets for treatment and symptom-relief in liver cirrhosis.&#xD;
&#xD;
      METHODS The cohort study will apply an observational prospective incidence cohort design in&#xD;
      which patients will be followed from diagnosis to death or withdrawal from the cohort.&#xD;
      Participants will be enrolled consecutively within six months of diagnosis.&#xD;
&#xD;
      TRIAL FLOW The standardized investigational program includes procedures recommended by&#xD;
      National- and European guidelines for complications in liver cirrhosis, applied at the Gastro&#xD;
      Unit, Medical Division, Amager Hvidovre Hospital.&#xD;
&#xD;
      The standard investigational program will be initiated within six months of inclusion. To&#xD;
      avoid repetition of invasive diagnostic procedures (e.g. upper endoscopy, CT scan or&#xD;
      ultrasound), we will accept retrospective inclusion of data, dating back to time of diagnosis&#xD;
      (maximum six months).&#xD;
&#xD;
      Standard biochemistry will be performed at inclusion and at follow-up after 1,2,3 and 5&#xD;
      years.&#xD;
&#xD;
      Bio Impedance Assessment will be performed at inclusion and at follow up after 1,2,3 and 5&#xD;
      years.&#xD;
&#xD;
      Assessments of socio demography, loneliness and quality of life will be performed through the&#xD;
      following questionnaires:&#xD;
&#xD;
        1. A specific questionnaire assessing socio demography, economic status and use of health&#xD;
           care resources is designed for the trial.&#xD;
&#xD;
        2. Three item loneliness scale&#xD;
&#xD;
        3. Alcohol use by Audit C&#xD;
&#xD;
        4. Health related quality of life in cirrhosis by: Chronic Liver Disease Questionnaire&#xD;
           (CLDQ).&#xD;
&#xD;
        5. Functional disability in work-, social- and family life by: Sheehan Disability Scale&#xD;
           (SDS).&#xD;
&#xD;
      Information will be retrieved from the participant's medical record concerning:&#xD;
&#xD;
        -  Dates and length of hospitalization.&#xD;
&#xD;
        -  Reason for hospitalization.&#xD;
&#xD;
        -  Diagnosis.&#xD;
&#xD;
        -  Biochemistry.&#xD;
&#xD;
        -  Results from endoscopic procedures.&#xD;
&#xD;
        -  Results from ultrasound, CT scan, and if applied, MR scan.&#xD;
&#xD;
        -  Results from Dexascan.&#xD;
&#xD;
      BIO BANK FOR FUTURE RESEARCH For this study a research bio bank for future research will be&#xD;
      established. The bio bank will contain blood, liver tissue and stool.&#xD;
&#xD;
      The bio bank is registered separately by The Danish Data Protection Agency.&#xD;
&#xD;
      DATA A database in Redcap will be established for the study. Questionnaires will be answered&#xD;
      electronically on an Ipad exporting data directly to Redcap. The Redcap database will use&#xD;
      study ID numbers and initials for identification of participants. An identification list of&#xD;
      all participants will be stored separately.&#xD;
&#xD;
      Investigators aim to publish all results derived from this trial. The investigators support&#xD;
      open acces policy, and at the end of the trial, all data will be sought published in&#xD;
      anonymous form.&#xD;
&#xD;
      ETHICS The study is approved by the Scientific Ethics Committees of the Capital Region of&#xD;
      Denmark and The Danish Data Protection Agency before initiation.&#xD;
&#xD;
      A thorough characterization and consecutive inclusion will strengthen our knowledge on the&#xD;
      incidence, prevalence and impact of liver disease in the population, and the use of health&#xD;
      care resources allocated to liver disease.&#xD;
&#xD;
      The study will contribute to the finding of formerly unidentified risk factors with&#xD;
      importance for survival and use of health care services; and thereby form the basis of&#xD;
      implementation of changes in health practices, with both economic and medical gain. The study&#xD;
      may also identify new areas for interventional research, with clinically relevant endpoints&#xD;
      that can be translated into favorable changes in health care practice.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 1, 2019</start_date>
  <completion_date type="Anticipated">December 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 30, 2024</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>5 Years</target_duration>
  <primary_outcome>
    <measure>Improve risk of decompensation in cirrhosis</measure>
    <time_frame>5 years</time_frame>
    <description>time to development of decompensation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Survival</measure>
    <time_frame>5 years</time_frame>
    <description>Time from diagnosis to death or liver transplantation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Risk prediction by Short Physical Performance Battery</measure>
    <time_frame>5 years</time_frame>
    <description>Identify patients with low physical performance and assess their risk of decompensation and complications to liver cirrhosis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Characterization of patients</measure>
    <time_frame>5 years</time_frame>
    <description>Describe characteristics of disease in the cohort</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Social impact of cirrhosis</measure>
    <time_frame>5 years</time_frame>
    <description>Assess the impact of social factors, use of health care ressources, including home nursing, with importance for early death and readmission</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Life space Assessment</measure>
    <time_frame>5 years</time_frame>
    <description>Evaluate mobility in cirrhosis by Life Space Assessment questionnaire</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">550</enrollment>
  <condition>Liver Cirrhosis, Alcoholic</condition>
  <condition>Progression</condition>
  <condition>Liver Diseases</condition>
  <condition>Decompensated Cirrhosis</condition>
  <arm_group>
    <arm_group_label>Cohort</arm_group_label>
    <description>Patients newly diagnosed with liver cirrhosis form the Gastro Unit, Amager Hvidovre Hospital, Denmark. All patients with clinically verified diagnosis, irrepsective of disease stage and etiology is included.</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Plasma and buffy coat from whole blood, liver biopsies, stool samples&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        All patients with a debut of liver cirrhosis, irrespective of time and circumstances of&#xD;
        diagnosis, comorbidities and severity of disease will be offered inclusion in the cohort.&#xD;
&#xD;
        A small percentage of patients will be diagnosed with cirrhosis at a very late stage of&#xD;
        disease and have complications compromising their cognitive function. When complications&#xD;
        are considered reversible, enrolment in the study will be sought when the patient has&#xD;
        recovered. When complications are considered irreversible or there may be reasonable doubt&#xD;
        of the patient's survival, patients will be considered eligible, but excluded to avoid&#xD;
        unethical conduction of procedures.&#xD;
&#xD;
        Participants may be diagnosed with terminal disease or end-stage liver disease. In such a&#xD;
        case, to secure the integrity of the patient, no extra investigational procedures will be&#xD;
        made and only data sampled in standard medical care will be used in the cohort database.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Clinical suspicion of cirrhosis supported by biochemistry and ultrasound or other&#xD;
             imaging techniques.&#xD;
&#xD;
          -  Cirrhosis of any etiology&#xD;
&#xD;
          -  Informed written consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  People where the diagnosis of liver cirrhosis is questioned with reasonable doubt or&#xD;
             the diagnosis of liver cirrhosis is disproved by histology or relevant imaging.&#xD;
&#xD;
          -  Withdrawal of informed consent or no informed consent.&#xD;
&#xD;
          -  Persons eligible for inclusion where the investigational program is delayed or not&#xD;
             initiated within six months after the diagnosis of suspected cirrhosis.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Nina Kimer, PhD</last_name>
    <phone>+4538621968</phone>
    <email>nina.kimer@regionh.dk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>LIse Hobolth, PhD</last_name>
    <email>lise.hobotlh@regionh.dk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Nina Kimer</name>
      <address>
        <city>Hvidovre</city>
        <state>Please Enter The State Or Province</state>
        <zip>2650</zip>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nina Kimer, PhD</last_name>
      <phone>+4538621968</phone>
      <email>nina.kimer@regionh.dk</email>
    </contact>
    <contact_backup>
      <last_name>Lise Hobolth, PhD</last_name>
      <email>lise.hobolth@regionh.dk</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 2, 2020</study_first_submitted>
  <study_first_submitted_qc>June 4, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>June 4, 2020</last_update_submitted>
  <last_update_submitted_qc>June 4, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 9, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Copenhagen University Hospital, Hvidovre</investigator_affiliation>
    <investigator_full_name>Nina Kimer</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <keyword>Prognosis</keyword>
  <keyword>Prospective</keyword>
  <keyword>Cirrhosis</keyword>
  <keyword>Hepatology</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Cirrhosis</mesh_term>
    <mesh_term>Liver Diseases</mesh_term>
    <mesh_term>Liver Cirrhosis, Alcoholic</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>We plan to share IPD in anonymuos form, in a data repository, possibly stored by the University of Copenhagen. Plans for the IPD derived from the biobank for future research will be made when protocols for these projects are completed.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>5-10 years</ipd_time_frame>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04422223
org study id: H-19024348
nct id: NCT04422223
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
A population based incidence cohort will enroll patients newly diagnosed with cirrhosis to
      investigate disease characteristics and outcomes, explore mechanisms predicting early death
      and hospital admission, and assess new monitoring tools in treatment and prevention of
      cirrhosis.
INTRODUCTION In Denmark the incidence of liver cirrhosis is increasing. From 1996 to 2005 the
      number of hospital admissions due to liver cirrhosis rose with 2,500 extra admissions per
      year. Patients who are readmitted to the hospital have a higher 90 days mortality than those
      who avoid readmission.

      Liver cirrhosis in Denmark is caused by a wide use of alcohol and a population increasing in
      age and BMI.

      The course of cirrhosis depends on etiology, age and nutritional status, as well as social
      factors such as personal network, employment and economy. Interventional studies on many of
      these mechanisms are still unexplored.

      Cirrhosis is related to decreased quality of life and affects patients and relatives both
      emotional and socioeconomically.

      The Gastro Unit, Amager Hvidovre Hospital has a catchment area of 550,000 citizens in South
      and West of Copenhagen. The Gastro Unit diagnoses app. 140 people with liver cirrhosis
      yearly.

      Patient education and rehabilitation is implemented as standard health care after significant
      pulmonary or cardiac disease in all regions of Denmark.

      HYPOTHESIS A systematic approach to investigation, treatment and rehabilitation in liver
      cirrhosis will improve the patient's ability to benefit from medical treatment and health
      care offers and increase patient involvement and autonomy in disease.

      A systematic approach to investigation of liver disease will contribute to identify new risk
      factors for death, hospital admission and readmission, and decompensation in liver cirrhosis.

      Better knowledge on sociodemographic features, use of health care resources and the patient's
      physical performance and frailty will improve new actions of personalized treatment,
      interventions focusing on patient needs and patient reported outcomes in cirrhosis.

      Primary outcome The primary aim for this prospective cohort study is to improve
      characterization, treatment and rehabilitation under and after admission of patients with
      liver cirrhosis, with the purpose of improving survival and reducing risk of readmission.

      Secondary outcomes

        -  To identify 'frail patients' and to improve their access to health care offers.

        -  To improve the utilization of health care resources by a systematic approach to patient
           characterization and treatment.

        -  To identify co-factors with importance for early death and readmission.

        -  To identify and explore new targets for treatment and symptom-relief in liver cirrhosis.

      METHODS The cohort study will apply an observational prospective incidence cohort design in
      which patients will be followed from diagnosis to death or withdrawal from the cohort.
      Participants will be enrolled consecutively within six months of diagnosis.

      TRIAL FLOW The standardized investigational program includes procedures recommended by
      National- and European guidelines for complications in liver cirrhosis, applied at the Gastro
      Unit, Medical Division, Amager Hvidovre Hospital.

      The standard investigational program will be initiated within six months of inclusion. To
      avoid repetition of invasive diagnostic procedures (e.g. upper endoscopy, CT scan or
      ultrasound), we will accept retrospective inclusion of data, dating back to time of diagnosis
      (maximum six months).

      Standard biochemistry will be performed at inclusion and at follow-up after 1,2,3 and 5
      years.

      Bio Impedance Assessment will be performed at inclusion and at follow up after 1,2,3 and 5
      years.

      Assessments of socio demography, loneliness and quality of life will be performed through the
      following questionnaires:

        1. A specific questionnaire assessing socio demography, economic status and use of health
           care resources is designed for the trial.

        2. Three item loneliness scale

        3. Alcohol use by Audit C

        4. Health related quality of life in cirrhosis by: Chronic Liver Disease Questionnaire
           (CLDQ).

        5. Functional disability in work-, social- and family life by: Sheehan Disability Scale
           (SDS).

      Information will be retrieved from the participant's medical record concerning:

        -  Dates and length of hospitalization.

        -  Reason for hospitalization.

        -  Diagnosis.

        -  Biochemistry.

        -  Results from endoscopic procedures.

        -  Results from ultrasound, CT scan, and if applied, MR scan.

        -  Results from Dexascan.

      BIO BANK FOR FUTURE RESEARCH For this study a research bio bank for future research will be
      established. The bio bank will contain blood, liver tissue and stool.

      The bio bank is registered separately by The Danish Data Protection Agency.

      DATA A database in Redcap will be established for the study. Questionnaires will be answered
      electronically on an Ipad exporting data directly to Redcap. The Redcap database will use
      study ID numbers and initials for identification of participants. An identification list of
      all participants will be stored separately.

      Investigators aim to publish all results derived from this trial. The investigators support
      open acces policy, and at the end of the trial, all data will be sought published in
      anonymous form.

      ETHICS The study is approved by the Scientific Ethics Committees of the Capital Region of
      Denmark and The Danish Data Protection Agency before initiation.

      A thorough characterization and consecutive inclusion will strengthen our knowledge on the
      incidence, prevalence and impact of liver disease in the population, and the use of health
      care resources allocated to liver disease.

      The study will contribute to the finding of formerly unidentified risk factors with
      importance for survival and use of health care services; and thereby form the basis of
      implementation of changes in health practices, with both economic and medical gain. The study
      may also identify new areas for interventional research, with clinically relevant endpoints
      that can be translated into favorable changes in health care practice.
observational model: Cohort
time perspective: Prospective
measure: Improve risk of decompensation in cirrhosis
time frame: 5 years
description: time to development of decompensation
measure: Survival
time frame: 5 years
description: Time from diagnosis to death or liver transplantation
measure: Risk prediction by Short Physical Performance Battery
time frame: 5 years
description: Identify patients with low physical performance and assess their risk of decompensation and complications to liver cirrhosis
measure: Characterization of patients
time frame: 5 years
description: Describe characteristics of disease in the cohort
measure: Social impact of cirrhosis
time frame: 5 years
description: Assess the impact of social factors, use of health care ressources, including home nursing, with importance for early death and readmission
measure: Life space Assessment
time frame: 5 years
description: Evaluate mobility in cirrhosis by Life Space Assessment questionnaire
arm group label: Cohort
description: Patients newly diagnosed with liver cirrhosis form the Gastro Unit, Amager Hvidovre Hospital, Denmark. All patients with clinically verified diagnosis, irrepsective of disease stage and etiology is included.
Plasma and buffy coat from whole blood, liver biopsies, stool samples
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Nina Kimer, PhD
phone: +4538621968
email: nina.kimer@regionh.dk
last name: LIse Hobolth, PhD
email: lise.hobotlh@regionh.dk
facility: 
status: Recruiting
contact: 
contact backup: 
country: Denmark
responsible party type: Principal Investigator
investigator affiliation: Copenhagen University Hospital, Hvidovre
investigator full name: Nina Kimer
investigator title: MD, PhD
mesh term: Liver Cirrhosis
mesh term: Liver Diseases
mesh term: Liver Cirrhosis, Alcoholic
mesh term: Fibrosis
sharing ipd: Yes
ipd description: We plan to share IPD in anonymuos form, in a data repository, possibly stored by the University of Copenhagen. Plans for the IPD derived from the biobank for future research will be made when protocols for these projects are completed.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Clinical Study Report (CSR)
ipd time frame: 5-10 years