<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/NCT02237495</url>
  </required_header>
  <id_info>
    <org_study_id>20140227-5</org_study_id>
    <nct_id>NCT02237495</nct_id>
  </id_info>
  <brief_title>Dexmedetomidine and Outcomes of Cardiac Surgery (DOCS)</brief_title>
  <acronym>DOCS</acronym>
  <official_title>Perioperative Infusion of Dexmedetomidine Improves Outcomes of Cardiovascular Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Xijing Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Xijing Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Cardiac surgery is associated with a high risk of cardiovascular and other complications. The&#xD;
      investigators hypothesized that perioperative infusion of dexmedetomidine may reduce the&#xD;
      incidence of complications and mortality following cardiovascular surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There are about 694,000 open-heart surgeries performed in US each year. The major&#xD;
      complication rates for valve plus coronary artery bypass graft (CABG) procedure are as high&#xD;
      as 30.1% in Society of Thoracic Surgeons (STS) reports. Postoperative delirium, infection,&#xD;
      acute renal failure (ARF) and major adverse cardiocerebral events (MACE) which include&#xD;
      permanent or transient stroke, coma, perioperative myocardial infarction (MI), heart block&#xD;
      and cardiac arrest represent the major postoperative complications. These complications&#xD;
      translate into increased mortality and prolonged hospital stays with estimated costs&#xD;
      exceeding $20 billion annually.6 The etiologies of these adverse events are multifactorial,&#xD;
      but one major contributing factor is the surgical stress responses that result in increasing&#xD;
      plasma levels of epinephrine and norepinephrine, with consequent myocardial oxygen supply&#xD;
      demand imbalance and myocardial ischemia. More than 50% of all perioperative complications&#xD;
      are related to adverse cardiovascular events.&#xD;
&#xD;
      The alpha-2 receptor agonists (clonidine, dexmedetomidine) currently used in clinical&#xD;
      practice have many desirable effects that may provide myocardial protection including&#xD;
      analgesia, anxiolysis, inhibition of central sympathetic outflow and reduction of systemic&#xD;
      norepinephrine release that improve hemodynamic stability and positively affect myocardial&#xD;
      oxygen supply and demand. The most widely studied alpha-2 agonist is clonidine, a long-acting&#xD;
      partial agonist with an alpha-2 to alpha-1 selectivity ratio of 39:1. However,&#xD;
      dexmedetomidine is a highly selective, shorter-acting intravenous alpha-2 agonist with an&#xD;
      alpha-2 to alpha-1 selectivity ratio of 1300:1.&#xD;
&#xD;
      Multiple studies have reported that dexmedetomidine has a protective effect on specific&#xD;
      organs including heart, brain, kidney and lungs. In addition, dexmedetomidine has been shown&#xD;
      to have anti-inflammatory properties decreasing mortality and attenuating plasma cytokine&#xD;
      concentrations in laboratory animals exposed to endotoxin in a dose-dependent fashion. The&#xD;
      investigators hypothesized that dexmedetomidine may provide myocardial, brain, renal and&#xD;
      immune function protection for cardiovascular surgical patients. The specific aim of this&#xD;
      study was to investigate whether the perioperative use of dexmedetomidine is associated with&#xD;
      improved outcomes and a decreased incidence in postoperative mortality, MACE or other&#xD;
      complications in patients undergoing open-heart surgery.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 9, 2014</start_date>
  <completion_date type="Actual">March 2018</completion_date>
  <primary_completion_date type="Actual">March 1, 2017</primary_completion_date>
  <phase>Phase 2/Phase 3</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>1-year all cause of mortality and major postoperative complications</measure>
    <time_frame>1 year after operation</time_frame>
    <description>Postoperative delirium, infection, acute renal failure (ARF) and major adverse cardiocerebral events (MACE) which includes permanent or transient stroke, coma, perioperative myocardial infarction (MI), heart block and cardiac arrest represent major postoperative complications.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>All cause mortality and major complications</measure>
    <time_frame>The participants will be tightly observed for the duration of hospital stay, an expected average of 10 days and at 30 days after operation,</time_frame>
    <description>Infection, renal failure, need for dialysis, and major adverse cardiocerebral events (MACE) which includes permanent or transient stroke, coma, perioperative myocardial infarction (MI), heart block and cardiac arrest represent major complications</description>
  </secondary_outcome>
  <other_outcome>
    <measure>postoperative hospital stay</measure>
    <time_frame>the number of days between the operation and discharge, an expected average of 12 days</time_frame>
    <description>Record the time of post operative stay</description>
  </other_outcome>
  <other_outcome>
    <measure>ICU-stay</measure>
    <time_frame>the number of days the patients stay in the ICU after surgery, an expected average of 3 days</time_frame>
    <description>It is the length of stay in ICU</description>
  </other_outcome>
  <other_outcome>
    <measure>Incidence of prolonged ventilation</measure>
    <time_frame>the duration of intubation is the time from trachea intubation to extubation, an expected average of 20 hours</time_frame>
    <description>Prolonged ventilation is defined as patients remaining on the ventilator for more than 48 hours</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1100</enrollment>
  <condition>Heart Valve Diseases</condition>
  <condition>Coronary Artery Disease</condition>
  <arm_group>
    <arm_group_label>Saline</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Normal saline as placebo is continuously infused right after anesthesia induction and lasts for 12 hrs with the same infusion rate as the comparator dexmedetomidine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>dexmedetomidine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>dexmedetomidine intravenous infusion starts right after anesthesia induction in the operating room and last for 12 hours into ICU with a infusion dose of 0.4 ug/kg/h. To avoid potential cause of bradycardia, no dexmedetomidine bolus is given.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>dexmedetomidine</intervention_name>
    <description>dexmedetomidine with the dose of 0.4 ug/kg/h is continuously infused right after anesthesia induction and lasts for 12 hrs.</description>
    <arm_group_label>dexmedetomidine</arm_group_label>
    <other_name>Precedex</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>The vehicle of dexmedetomidine, normal saline is continuously infused right after anesthesia induction and lasts for 12 hrs with the same rate of the treatment arm.</description>
    <arm_group_label>Saline</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Provide written informed consent&#xD;
&#xD;
          -  Are &gt; 18 years of age&#xD;
&#xD;
          -  Elective cardiac surgery with CPB, when the surgeon plans to do valve and/or CABG&#xD;
             surgery&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Emergent cardiac surgery&#xD;
&#xD;
          -  Other than CABG and/or Valve surgery&#xD;
&#xD;
          -  off-pump or robotic surgery&#xD;
&#xD;
          -  Surgery requiring deep hypothermic circulatory arrest or involving the thoracic aorta&#xD;
&#xD;
          -  Life expectancy &lt; 1 year&#xD;
&#xD;
          -  Preop severe liver or renal dysfunction, with replacement therapy required&#xD;
&#xD;
          -  Patients with IABP or with cardiogenic shock&#xD;
&#xD;
          -  Severe dehydrate or dystrophia or Hb &lt; 10 g/dl&#xD;
&#xD;
          -  History of any alpha-2 receptor agonists allergy.&#xD;
&#xD;
          -  Refuse to provide written informed consent&#xD;
&#xD;
          -  Diagnosed with mental illness&#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_official>
    <last_name>Hailong Dong, M.D., Ph.D.,</last_name>
    <role>Study Chair</role>
    <affiliation>Xijing Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Xijing Hospital</name>
      <address>
        <city>Xi'an</city>
        <state>Shaanxi</state>
        <zip>710032</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>August 18, 2014</study_first_submitted>
  <study_first_submitted_qc>September 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 11, 2014</study_first_posted>
  <last_update_submitted>July 5, 2020</last_update_submitted>
  <last_update_submitted_qc>July 5, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 8, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Xijing Hospital</investigator_affiliation>
    <investigator_full_name>chonglei</investigator_full_name>
    <investigator_title>M.D., PhD</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Coronary Artery Disease</mesh_term>
    <mesh_term>Heart Valve Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexmedetomidine</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/NCT02237495
org study id: 20140227-5
nct id: NCT02237495
lead sponsor: 
has dmc: Yes
Cardiac surgery is associated with a high risk of cardiovascular and other complications. The
      investigators hypothesized that perioperative infusion of dexmedetomidine may reduce the
      incidence of complications and mortality following cardiovascular surgery.
There are about 694,000 open-heart surgeries performed in US each year. The major
      complication rates for valve plus coronary artery bypass graft (CABG) procedure are as high
      as 30.1% in Society of Thoracic Surgeons (STS) reports. Postoperative delirium, infection,
      acute renal failure (ARF) and major adverse cardiocerebral events (MACE) which include
      permanent or transient stroke, coma, perioperative myocardial infarction (MI), heart block
      and cardiac arrest represent the major postoperative complications. These complications
      translate into increased mortality and prolonged hospital stays with estimated costs
      exceeding $20 billion annually.6 The etiologies of these adverse events are multifactorial,
      but one major contributing factor is the surgical stress responses that result in increasing
      plasma levels of epinephrine and norepinephrine, with consequent myocardial oxygen supply
      demand imbalance and myocardial ischemia. More than 50% of all perioperative complications
      are related to adverse cardiovascular events.

      The alpha-2 receptor agonists (clonidine, dexmedetomidine) currently used in clinical
      practice have many desirable effects that may provide myocardial protection including
      analgesia, anxiolysis, inhibition of central sympathetic outflow and reduction of systemic
      norepinephrine release that improve hemodynamic stability and positively affect myocardial
      oxygen supply and demand. The most widely studied alpha-2 agonist is clonidine, a long-acting
      partial agonist with an alpha-2 to alpha-1 selectivity ratio of 39:1. However,
      dexmedetomidine is a highly selective, shorter-acting intravenous alpha-2 agonist with an
      alpha-2 to alpha-1 selectivity ratio of 1300:1.

      Multiple studies have reported that dexmedetomidine has a protective effect on specific
      organs including heart, brain, kidney and lungs. In addition, dexmedetomidine has been shown
      to have anti-inflammatory properties decreasing mortality and attenuating plasma cytokine
      concentrations in laboratory animals exposed to endotoxin in a dose-dependent fashion. The
      investigators hypothesized that dexmedetomidine may provide myocardial, brain, renal and
      immune function protection for cardiovascular surgical patients. The specific aim of this
      study was to investigate whether the perioperative use of dexmedetomidine is associated with
      improved outcomes and a decreased incidence in postoperative mortality, MACE or other
      complications in patients undergoing open-heart surgery.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Double (Participant, Investigator)
measure: 1-year all cause of mortality and major postoperative complications
time frame: 1 year after operation
description: Postoperative delirium, infection, acute renal failure (ARF) and major adverse cardiocerebral events (MACE) which includes permanent or transient stroke, coma, perioperative myocardial infarction (MI), heart block and cardiac arrest represent major postoperative complications.
measure: All cause mortality and major complications
time frame: The participants will be tightly observed for the duration of hospital stay, an expected average of 10 days and at 30 days after operation,
description: Infection, renal failure, need for dialysis, and major adverse cardiocerebral events (MACE) which includes permanent or transient stroke, coma, perioperative myocardial infarction (MI), heart block and cardiac arrest represent major complications
measure: postoperative hospital stay
time frame: the number of days between the operation and discharge, an expected average of 12 days
description: Record the time of post operative stay
measure: ICU-stay
time frame: the number of days the patients stay in the ICU after surgery, an expected average of 3 days
description: It is the length of stay in ICU
measure: Incidence of prolonged ventilation
time frame: the duration of intubation is the time from trachea intubation to extubation, an expected average of 20 hours
description: Prolonged ventilation is defined as patients remaining on the ventilator for more than 48 hours
arm group label: Saline
arm group type: Placebo Comparator
description: Normal saline as placebo is continuously infused right after anesthesia induction and lasts for 12 hrs with the same infusion rate as the comparator dexmedetomidine
arm group label: dexmedetomidine
arm group type: Experimental
description: dexmedetomidine intravenous infusion starts right after anesthesia induction in the operating room and last for 12 hours into ICU with a infusion dose of 0.4 ug/kg/h. To avoid potential cause of bradycardia, no dexmedetomidine bolus is given.
intervention type: Drug
intervention name: dexmedetomidine
description: dexmedetomidine with the dose of 0.4 ug/kg/h is continuously infused right after anesthesia induction and lasts for 12 hrs.
arm group label: dexmedetomidine
other name: Precedex
intervention type: Drug
intervention name: placebo
description: The vehicle of dexmedetomidine, normal saline is continuously infused right after anesthesia induction and lasts for 12 hrs with the same rate of the treatment arm.
arm group label: Saline
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Hailong Dong, M.D., Ph.D.,
role: Study Chair
affiliation: Xijing Hospital
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Xijing Hospital
investigator full name: chonglei
investigator title: M.D., PhD
mesh term: Coronary Artery Disease
mesh term: Heart Valve Diseases
mesh term: Dexmedetomidine