<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/NCT03763084</url>
  </required_header>
  <id_info>
    <org_study_id>2018071027</org_study_id>
    <nct_id>NCT03763084</nct_id>
  </id_info>
  <brief_title>Impact of Acetaminophen on Postoperative Delirium Elderly Patients After Non-cardiac Surgery</brief_title>
  <official_title>Impact of Oral Acetaminophen Analgesia on Postoperative Delirium and Long-term Survival in Elderly Patients After Non-cardiac Surgery: A Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Xiangya Hospital of Central South University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Yale University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Xiangya Hospital of Central South University</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      To investigate the impact of acetaminophen analgesia on the frequency of postoperative&#xD;
      delirium and 28 days mortality in elderly patients after noncardiac surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background: Delirium is a common complication following surgery contributes to adverse&#xD;
      outcomes, including increased mortality and morbidity, longer length of ICU stays, prolonged&#xD;
      mechanical ventilation, and costlier hospitalizations. Previous studies showed that, the&#xD;
      incidence of delirium for seniors patients admitted to ICU can reach up to 58%-75.6%&#xD;
      depending on the patient population and screening instrument. The current protocols for&#xD;
      perioperative opioid use and postoperative pain management may influence the occurrence of&#xD;
      delirium. We hypothesize that the use of oral acetaminophen (OVA) may lead to reduced opioid&#xD;
      consumption and decreased incidence of postoperative delirium.&#xD;
&#xD;
      Objectives: To investigate the impact of acetaminophen analgesia on the frequency of&#xD;
      postoperative delirium and 28 days mortality in elderly patients after noncardiac surgery.&#xD;
&#xD;
      Study design: A randomized and controlled trial. Setting: Departments of critical care&#xD;
      medicine of tertiary hospital (Xiangya) in China.&#xD;
&#xD;
      Patients: 164 elderly patients (≥ 65 years) who are scheduled to admitted to ICU after major&#xD;
      surgery (predicted duration ≥ 2 hours) Intervention: For patients in the acetaminophen group,&#xD;
      oral acetaminophen supplemented dexmedetomidine sedation will be provided after surgery. For&#xD;
      patients in the control group, sufentanil supplemented dexmedetomidine sedation will be&#xD;
      provided after surgery. the other analgesia drugs will be provided as back up in study group.&#xD;
&#xD;
      Primary outcome: Early primary endpoint is the frequency of delirium in the first 5-days&#xD;
      post-surgery. Secondary endpoints include biomark and NeuroMonitoring of delirium, 28days and&#xD;
      in-hospital mortality, length of stay days in ICU and hospital, complication in hospital.&#xD;
&#xD;
      Predicted duration of the study: 2 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">February 15, 2019</start_date>
  <completion_date type="Anticipated">November 1, 2020</completion_date>
  <primary_completion_date type="Anticipated">February 1, 2020</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Frequency of delirium</measure>
    <time_frame>within the first 5 postoperative days</time_frame>
    <description>evaluate the occurence of delirium by using Confusion Assessment Method for The Intensive Care Unit (CAM-ICU)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Effectiveness of analgesia</measure>
    <time_frame>during postoperative days 1-5</time_frame>
    <description>to assess the effect of analgesia by using Numerical Rating Scale (NRS)；This method is composed of 0 to 10, a total of 11 Numbers. Patients with 0 to 10 this digital describe pain intensity, the greater the number the pain degree is more serious.0 painless, 1 ~ 3 mild pain (pain does not affect sleep), 4 ~ 6 moderate pain, 7 ~ 9 severe pain (couldn't sleep), 10 severe pain. We should ask the patient pain degree, tag, or let the patient draw one of the most can represent their own pain degree of digital.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of days in ICU and hospital stay after surgery</measure>
    <time_frame>from day 1 after surgery to discharge (up to 24 weeks)</time_frame>
    <description>evaluate the length of days in ICU and hospital stay from postoperative to discharge</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of non-delirium complications</measure>
    <time_frame>with 28 days after surgery</time_frame>
    <description>Incidence of non-delirium complications with 28 days after surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All-cause28-day mortality</measure>
    <time_frame>day 28 after surgery</time_frame>
    <description>All-cause28-day mortality</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>life-Quality evaluation of 28-day survivors</measure>
    <time_frame>day 28 after surgery</time_frame>
    <description>evaluate the quality of life by using the world health organization quality of life measurement scale(WHOQOL-BREF). WHOQOL-BREF contains 26 items, summarizes the physiological, psychological, social relations, the environment in the field of four content.Consists of two independent analysis problem items: question 1 (G1) ask individual about their quality of life of the general subjective feeling, question 2 (G4) individual asked the total subjective feeling bout their own health. Domain scores are the positive (i.e., the higher the score, the better the quality of life).Field scoring through the calculation of average of their entries 4 times. and patients will be assessed via phone call if they are discharged before day 28 after surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive function of 28-day survivors</measure>
    <time_frame>day 28 after surgery</time_frame>
    <description>evaluate the cognitive function of 28-day survivors by using modified version of the telephone questionnaire for cognitive function questionnaire (TICS-m);It contains 21 items, total score 50 points, can be divided into three parts: the memory part (score 20), directional force (score 13), the capablity of language, and pay attention (score 17). TICS -m total score 50 points, scored &lt; 28 divided into dementia, 28 and 33 were divided into mild cognitive dysfunction, ≥33 were divided into normal. Patients will be assessed via phone call if they are discharged before day 28 after surgery</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">164</enrollment>
  <condition>Acetaminophen</condition>
  <condition>Delirium in Old Age</condition>
  <arm_group>
    <arm_group_label>acetaminophen</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>For patients randomized to OVA group, OVA 500mg was given every 8 hours for the first 48 hours postoperatively. Numeric Pain Rating Scale pain score is assessed every 15 minutes during the 1 hour of ICU stay and when needed.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sufentanil</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Sufentanil injection 500μg /10ml in normal saline, total volume 50 ml.Constant infusion dosage is 0.05μg/kg/h. Numeric Pain Rating Scale pain score is assessed every 15 minutes during the 1 hour of ICU stay and when needed.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Acetaminophen</intervention_name>
    <description>For patients in the acetaminophen group, oral acetaminophen supplemented dexmedetomidine sedation will be provided after surgery.</description>
    <arm_group_label>acetaminophen</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sufentanil</intervention_name>
    <description>For patients in the control group, sufentanil supplemented dexmedetomidine sedation will be provided after surgery.</description>
    <arm_group_label>Sufentanil</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Scheduled to ICU after non-cardiac surgery for any reasons；&#xD;
&#xD;
          2. Report having moderate to severe acute pain as determined by a pain score ≥ 5 from the&#xD;
             11-point Numeric Pain Rating Scale (NPRS) scale after postsurgery；&#xD;
&#xD;
          3. Able to take oral medication or by stomach tube；&#xD;
&#xD;
          4. Provide written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who meet any of the following criteria will be excluded.&#xD;
&#xD;
               1. Preoperative history of schizophrenia, epilepsy, Parkinsonism, or myasthenia&#xD;
                  gravis;&#xD;
&#xD;
               2. Inability to communicate in the preoperative period because of coma, profound&#xD;
                  dementia or language barrier;&#xD;
&#xD;
               3. Brain injury or neurosurgery;&#xD;
&#xD;
               4. Severe hepatic dysfunction (eg, aspartate aminotransferase, alanine&#xD;
                  aminotransferase, or bilirubin greater than or equal to 3.0 times the upper limit&#xD;
                  of normal), active hepatic disease, evidence of clinically significant liver&#xD;
                  disease, or other condition (eg, alcoholism, cirrhosis, or hepatitis) that&#xD;
                  suggests the potential for an increased susceptibility to hepatic toxicity with&#xD;
                  study drug exposure.&#xD;
&#xD;
               5. Subject has a positive test result for drugs of abuse (amphetamines,&#xD;
                  barbiturates, benzodiazepines, cannabinoids, cocaine, methamphetamine, methadone,&#xD;
                  or methylenedioxy-methamphetamine) at Screening.&#xD;
&#xD;
               6. Subject has participated in another clinical study within 30 days prior to&#xD;
                  day-of-surgery or plans to participate in another clinical study while&#xD;
                  concurrently enrolled in this study.&#xD;
&#xD;
               7. Subject has a history of any drug allergy, hypersensitivity, or intolerance to&#xD;
                  acetaminophen or morphine or to any of the excipients in the IV or oral&#xD;
                  formulations used.&#xD;
&#xD;
               8. Subject has intra- or postoperative complications, which in the view of the&#xD;
                  investigator, makes the subject unsuitable for the participation of the study.&#xD;
&#xD;
               9. Subject has a history of any drug allergy, hypersensitivity, or intolerance to&#xD;
                  acetaminophen or opioid or to any of the excipients in the IV or oral&#xD;
                  formulations used.&#xD;
&#xD;
              10. Unable to take medications orally or by stomach tube&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Yuhang Ai, Prof.</last_name>
    <phone>8613908480631</phone>
    <email>ayhicu1978@sina.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Xiangya Hospital, Central South University</name>
      <address>
        <city>Changsha</city>
        <state>Hunan</state>
        <zip>410000</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Xiao</last_name>
      <email>xyyyllwyh@126.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>December 2, 2018</study_first_submitted>
  <study_first_submitted_qc>December 2, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 4, 2018</study_first_posted>
  <last_update_submitted>March 6, 2019</last_update_submitted>
  <last_update_submitted_qc>March 6, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 8, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>acetaminophen</keyword>
  <keyword>analgesia</keyword>
  <keyword>delirium</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Delirium</mesh_term>
    <mesh_term>Emergence Delirium</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acetaminophen</mesh_term>
    <mesh_term>Sufentanil</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03763084
org study id: 2018071027
nct id: NCT03763084
lead sponsor: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
To investigate the impact of acetaminophen analgesia on the frequency of postoperative
      delirium and 28 days mortality in elderly patients after noncardiac surgery.
Background: Delirium is a common complication following surgery contributes to adverse
      outcomes, including increased mortality and morbidity, longer length of ICU stays, prolonged
      mechanical ventilation, and costlier hospitalizations. Previous studies showed that, the
      incidence of delirium for seniors patients admitted to ICU can reach up to 58%-75.6%
      depending on the patient population and screening instrument. The current protocols for
      perioperative opioid use and postoperative pain management may influence the occurrence of
      delirium. We hypothesize that the use of oral acetaminophen (OVA) may lead to reduced opioid
      consumption and decreased incidence of postoperative delirium.

      Objectives: To investigate the impact of acetaminophen analgesia on the frequency of
      postoperative delirium and 28 days mortality in elderly patients after noncardiac surgery.

      Study design: A randomized and controlled trial. Setting: Departments of critical care
      medicine of tertiary hospital (Xiangya) in China.

      Patients: 164 elderly patients (≥ 65 years) who are scheduled to admitted to ICU after major
      surgery (predicted duration ≥ 2 hours) Intervention: For patients in the acetaminophen group,
      oral acetaminophen supplemented dexmedetomidine sedation will be provided after surgery. For
      patients in the control group, sufentanil supplemented dexmedetomidine sedation will be
      provided after surgery. the other analgesia drugs will be provided as back up in study group.

      Primary outcome: Early primary endpoint is the frequency of delirium in the first 5-days
      post-surgery. Secondary endpoints include biomark and NeuroMonitoring of delirium, 28days and
      in-hospital mortality, length of stay days in ICU and hospital, complication in hospital.

      Predicted duration of the study: 2 years.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Frequency of delirium
time frame: within the first 5 postoperative days
description: evaluate the occurence of delirium by using Confusion Assessment Method for The Intensive Care Unit (CAM-ICU)
measure: Effectiveness of analgesia
time frame: during postoperative days 1-5
description: to assess the effect of analgesia by using Numerical Rating Scale (NRS)；This method is composed of 0 to 10, a total of 11 Numbers. Patients with 0 to 10 this digital describe pain intensity, the greater the number the pain degree is more serious.0 painless, 1 ~ 3 mild pain (pain does not affect sleep), 4 ~ 6 moderate pain, 7 ~ 9 severe pain (couldn't sleep), 10 severe pain. We should ask the patient pain degree, tag, or let the patient draw one of the most can represent their own pain degree of digital.
measure: Length of days in ICU and hospital stay after surgery
time frame: from day 1 after surgery to discharge (up to 24 weeks)
description: evaluate the length of days in ICU and hospital stay from postoperative to discharge
measure: Incidence of non-delirium complications
time frame: with 28 days after surgery
description: Incidence of non-delirium complications with 28 days after surgery
measure: All-cause28-day mortality
time frame: day 28 after surgery
description: All-cause28-day mortality
measure: life-Quality evaluation of 28-day survivors
time frame: day 28 after surgery
description: evaluate the quality of life by using the world health organization quality of life measurement scale(WHOQOL-BREF). WHOQOL-BREF contains 26 items, summarizes the physiological, psychological, social relations, the environment in the field of four content.Consists of two independent analysis problem items: question 1 (G1) ask individual about their quality of life of the general subjective feeling, question 2 (G4) individual asked the total subjective feeling bout their own health. Domain scores are the positive (i.e., the higher the score, the better the quality of life).Field scoring through the calculation of average of their entries 4 times. and patients will be assessed via phone call if they are discharged before day 28 after surgery
measure: Cognitive function of 28-day survivors
time frame: day 28 after surgery
description: evaluate the cognitive function of 28-day survivors by using modified version of the telephone questionnaire for cognitive function questionnaire (TICS-m);It contains 21 items, total score 50 points, can be divided into three parts: the memory part (score 20), directional force (score 13), the capablity of language, and pay attention (score 17). TICS -m total score 50 points, scored < 28 divided into dementia, 28 and 33 were divided into mild cognitive dysfunction, ≥33 were divided into normal. Patients will be assessed via phone call if they are discharged before day 28 after surgery
arm group label: acetaminophen
arm group type: Experimental
description: For patients randomized to OVA group, OVA 500mg was given every 8 hours for the first 48 hours postoperatively. Numeric Pain Rating Scale pain score is assessed every 15 minutes during the 1 hour of ICU stay and when needed.
arm group label: Sufentanil
arm group type: Active Comparator
description: Sufentanil injection 500μg /10ml in normal saline, total volume 50 ml.Constant infusion dosage is 0.05μg/kg/h. Numeric Pain Rating Scale pain score is assessed every 15 minutes during the 1 hour of ICU stay and when needed.
intervention type: Drug
intervention name: Acetaminophen
description: For patients in the acetaminophen group, oral acetaminophen supplemented dexmedetomidine sedation will be provided after surgery.
arm group label: acetaminophen
intervention type: Drug
intervention name: Sufentanil
description: For patients in the control group, sufentanil supplemented dexmedetomidine sedation will be provided after surgery.
arm group label: Sufentanil
criteria: 
gender: All
minimum age: 65 Years
maximum age: N/A
healthy volunteers: No
last name: Yuhang Ai, Prof.
phone: 8613908480631
email: ayhicu1978@sina.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Delirium
mesh term: Emergence Delirium
mesh term: Acetaminophen
mesh term: Sufentanil