<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/NCT01704430</url>
  </required_header>
  <id_info>
    <org_study_id>MAZ_CVICU_001</org_study_id>
    <nct_id>NCT01704430</nct_id>
  </id_info>
  <brief_title>Glutamine to Improve Outcomes in Cardiac Surgery</brief_title>
  <acronym>GLADIATOR</acronym>
  <official_title>GLutamine Enterally After carDiac Surgery for Inflammation Attenuation and ouTcOme impRovement (GLADIATOR): A Phase II Randomized, Blinded, Placebo-Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Alberta</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Alberta</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients undergoing heart surgery with a heart-lung machine (termed cardiopulmonary bypass)&#xD;
      are at an increased risk of having abnormal &quot;inflammation&quot; in their body after surgery. Such&#xD;
      inflammation can contribute to slower recovery from surgery, an increased risk of infection,&#xD;
      an increased risk of damage to organs other than the heart, and a more complicated course.&#xD;
&#xD;
      Prior research has suggested that using an oral protein supplement made of glutamine (an&#xD;
      essential amino acid normally found in your body) can reduce the risk of inflammation,&#xD;
      infection and the length of stay in hospital in patients who have suffered major trauma or a&#xD;
      burn injury. The investigators believe reducing such inflammation after heart surgery may&#xD;
      help promote recovery and reduce the risk of adverse events and complications.&#xD;
&#xD;
      The purpose of this preliminary study is to see if oral glutamine supplementation after heart&#xD;
      surgery is practical, and contributes to a reduction in inflammation. The oral glutamine&#xD;
      proposed in this study is based on what has been previously studied and what is considered&#xD;
      safe.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hypothesis: We believe that early post-operative administration of enteral glutamine&#xD;
      following cardiac surgery with cardiopulmonary bypass (CPB) in high risk patients will reduce&#xD;
      inflammation and nonscomial infections, reduce length of ventilator support, reduce need for&#xD;
      vasoactive support, reduce secondary organ dysfunction, reduce length of hospital stay in the&#xD;
      CVICU, and reduce mortality.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
        -  To assess the feasibility of early glutamine supplementation&#xD;
&#xD;
        -  To evaluate the safety profile of early glutamine supplementation&#xD;
&#xD;
        -  To evaluate efficacy the impact of early glutamine on clinically important&#xD;
           post-operative complications and outcomes, including: systemic inflammation, nosocomial&#xD;
           infections, mortality, and health resource utilization&#xD;
&#xD;
      Methods: Study Design, Setting, and Patient Population: The proposed study is a Phase II,&#xD;
      randomized, blinded, placebo-controlled trial. This trial will be performed in the&#xD;
      Cardiovascular Surgical Intensive Care Unit (CVICU) of the Mazankowski Alberta Heart&#xD;
      Institute (MAHI), Alberta Health Services. The proposed trial plans to enroll 100 consecutive&#xD;
      eligible patients.&#xD;
&#xD;
      Inclusion:&#xD;
&#xD;
        -  Consent (obtained pre-operatively)&#xD;
&#xD;
        -  Adult - aged 18 years or older;&#xD;
&#xD;
        -  Planned cardiac surgery with CPB;&#xD;
&#xD;
        -  Elevated risk for post-operative morbidity, defined by a pre-operative European System&#xD;
           for Operative Cardiac Risk Evaluation (EuroSCORE) &gt; 6.&#xD;
&#xD;
        -  Able to receive enteral nutrition through nasal/oral gastric or post-pyloric feeding&#xD;
           tube.&#xD;
&#xD;
      Exclusion:&#xD;
&#xD;
        -  Planned heart or lung transplantation&#xD;
&#xD;
        -  Planned cardiac surgery without cardiopulmonary bypass;&#xD;
&#xD;
        -  Peri-operative support with extracorporeal membrane oxygenation (ECMO) or left&#xD;
           ventricular assist device (LVAD).&#xD;
&#xD;
      Study Protocol: Eligible patients will be identified during pre-operative assessment in the&#xD;
      pre-operative clinic (PAC). All eligible patients or their surrogate decision-making/legal&#xD;
      guardian will then be approached to obtain informed written consent.&#xD;
&#xD;
      Each consenting participant will be randomly allocated (1:1) to receive post-operative&#xD;
      enteral glutamine or identical placebo. Investigators, surgeons, intensivists, bedside nurses&#xD;
      and participants will remain blinded to study allocation.&#xD;
&#xD;
      Glutamine supplementation will be dosed at 0.5 g/kg satisfactory body weight (SBW)/day&#xD;
      divided every 8 hours, starting 6 hours post-operatively and continued for 5 days. The dose&#xD;
      of 0.5 g/kg SBW/day was effective in clinical studies using enteral glutamine in critically&#xD;
      ill and/or burn injured and major trauma patients. The glutamine supplementation or placebo&#xD;
      will be delivered via naso- or oro-gastric feeding tube after confirmation of placement by&#xD;
      chest X-ray. For participants who are extubated prior to 5 days, enteral glutamine will be&#xD;
      given by mouth for the duration of the 5 day period. Glutamine and placebo will be mixed in&#xD;
      orange juice to maintain blinding.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">June 21, 2016</completion_date>
  <primary_completion_date type="Actual">June 21, 2016</primary_completion_date>
  <phase>N/A</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>
    <intervention_model_description>Glutamine</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of Eligible Patients Providing Consent to Participate</measure>
    <time_frame>Date of surgery until date of hospital discharge, an expected average of 2 weeks</time_frame>
    <description>Assess the FEASIBILITY of the protocol to (i) achieve &gt;75% consent rate in eligible patients</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Acute Kidney Injury</measure>
    <time_frame>Date of surgery until date of hospital discharge, an expected average of 2 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of mechanical ventilation</measure>
    <time_frame>Date of surgery until date of hospital discharge, an expected average of 2 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of vasoactive support</measure>
    <time_frame>Date of surgery until date of hospital discharge, an expected average of 2 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood transfusion</measure>
    <time_frame>Date of surgery until date of hospital discharge, an expected average of 2 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Organ Dysfunction Score</measure>
    <time_frame>Date of surgery until date of hospital discharge, an expected average of 2 weeks</time_frame>
    <description>Post-operative changes to the Sequential Organ Failure Assessment score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>Date of surgery until date of hospital discharge, an expected average of 2 weeks</time_frame>
    <description>Evaluate the SAFETY and ADVERSE EFFECTS of (i) enteral glutamine; and (ii) COMPLICATIONS from feeding tube placement, including: epistaxis, feeding tube malposition, pneumothorax, esophageal injury, gastric mucosal irritation, gastrointestinal bleeding, unplanned feeding tube removal, and need for feeding tube reinsertion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Systemic inflammation</measure>
    <time_frame>Date of surgery until the end of planned study intervention, expected 5-days</time_frame>
    <description>Systemic Inflammation/immunomodulation: We will evaluate for increases and changes in systemic inflammation stratified by study intervention. This will aid in providing proof-of-concept of the biologic plausibility of the study intervention. The investigators propose to evaluate serial measures of C-reactive protein (CRP), chemiluminescent endotoxin activity assay (EAA), and interleukin-6 (IL-6).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Nosocomial infection</measure>
    <time_frame>Date of surgery until date of hospital discharge, an expected average of 2 weeks</time_frame>
    <description>Nosocomial infections: The investigators will specifically examine for the following infections during the period of hospitalization after surgery: superficial and deep sternal wound infections; mediastinitis; saphenous vein graft harvest site wound infections; ventilator associated and hospital acquired pneumonia; urinary tract infections; bloodstream infections; catheter-related blood stream infections; and decubitus ulcers.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of Randomized Patients Achieving Protocol Adherence</measure>
    <time_frame>5-days (date of surgery until the end of planned study intervention)</time_frame>
    <description>Obtain &gt; 90% protocol adherence</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Mortality</measure>
    <time_frame>From the Date of Surgery until Date of Death or 90-days, whichever occurs first</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Duration of ICU stay</measure>
    <time_frame>Date of surgery until date of hospital discharge, an expected average of 2 weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Duration of hospital stay</measure>
    <time_frame>Date of surgery until date of hospital discharge, an expected average of 2 weeks</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Nosocomial Infection</condition>
  <arm_group>
    <arm_group_label>Glutamine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral/enteral glutamine 0.5 g/kg satisfactory body weight per day (divided doses every 8 hours) starting 6 hours post-operatively</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Maltodextrin</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Oral/enteral maltodextrin 0.5 g/kg satisfactory body weight per day (divided doses every 8 hours) starting 6 hours post-operatively</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Glutamine</intervention_name>
    <description>Enteric L-Glutamine</description>
    <arm_group_label>Glutamine</arm_group_label>
    <other_name>L-Glutamine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Maltodextrin</intervention_name>
    <description>Enteric Maltodextrin</description>
    <arm_group_label>Maltodextrin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Consent (obtained pre-operatively)&#xD;
&#xD;
          -  Adult - aged 18 years or older;&#xD;
&#xD;
          -  Planned cardiovascular surgery with cardiopulmonary bypass;&#xD;
&#xD;
          -  Increased risk for post-operative morbidity, defined by a pre-operative European&#xD;
             System for Operative Cardiac Risk Evaluation (EuroSCORE) &gt; 6;&#xD;
&#xD;
          -  Able to receive enteral nutrition through nasal/oral gastric or post-pyloric feeding&#xD;
             tube.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Planned heart or lung transplantation&#xD;
&#xD;
          -  Planned cardiovascular surgery without cardiopulmonary bypass;&#xD;
&#xD;
          -  Peri-operative support with extracorporeal membrane oxygenation (ECMO) or left&#xD;
             ventricular assist device (LVAD).&#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>Sean Bagshaw</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Alberta</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Gurmeet Singh</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Alberta</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Alberta</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G 2B7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mazankowski Alberta Heart Institute, University of Alberta</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G2B7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>February 2017</verification_date>
  <study_first_submitted>August 22, 2012</study_first_submitted>
  <study_first_submitted_qc>October 9, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 11, 2012</study_first_posted>
  <last_update_submitted>February 6, 2017</last_update_submitted>
  <last_update_submitted_qc>February 6, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 8, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cardiac surgery</keyword>
  <keyword>Cardiac bypass</keyword>
  <keyword>Intensive Care</keyword>
  <keyword>Nosocomial infection</keyword>
  <keyword>Glutamine</keyword>
  <keyword>Randomized trial</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cross Infection</mesh_term>
  </condition_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/NCT01704430
org study id: MAZ_CVICU_001
nct id: NCT01704430
lead sponsor: 
has dmc: No
Patients undergoing heart surgery with a heart-lung machine (termed cardiopulmonary bypass)
      are at an increased risk of having abnormal "inflammation" in their body after surgery. Such
      inflammation can contribute to slower recovery from surgery, an increased risk of infection,
      an increased risk of damage to organs other than the heart, and a more complicated course.

      Prior research has suggested that using an oral protein supplement made of glutamine (an
      essential amino acid normally found in your body) can reduce the risk of inflammation,
      infection and the length of stay in hospital in patients who have suffered major trauma or a
      burn injury. The investigators believe reducing such inflammation after heart surgery may
      help promote recovery and reduce the risk of adverse events and complications.

      The purpose of this preliminary study is to see if oral glutamine supplementation after heart
      surgery is practical, and contributes to a reduction in inflammation. The oral glutamine
      proposed in this study is based on what has been previously studied and what is considered
      safe.
Hypothesis: We believe that early post-operative administration of enteral glutamine
      following cardiac surgery with cardiopulmonary bypass (CPB) in high risk patients will reduce
      inflammation and nonscomial infections, reduce length of ventilator support, reduce need for
      vasoactive support, reduce secondary organ dysfunction, reduce length of hospital stay in the
      CVICU, and reduce mortality.

      Objectives:

        -  To assess the feasibility of early glutamine supplementation

        -  To evaluate the safety profile of early glutamine supplementation

        -  To evaluate efficacy the impact of early glutamine on clinically important
           post-operative complications and outcomes, including: systemic inflammation, nosocomial
           infections, mortality, and health resource utilization

      Methods: Study Design, Setting, and Patient Population: The proposed study is a Phase II,
      randomized, blinded, placebo-controlled trial. This trial will be performed in the
      Cardiovascular Surgical Intensive Care Unit (CVICU) of the Mazankowski Alberta Heart
      Institute (MAHI), Alberta Health Services. The proposed trial plans to enroll 100 consecutive
      eligible patients.

      Inclusion:

        -  Consent (obtained pre-operatively)

        -  Adult - aged 18 years or older;

        -  Planned cardiac surgery with CPB;

        -  Elevated risk for post-operative morbidity, defined by a pre-operative European System
           for Operative Cardiac Risk Evaluation (EuroSCORE) > 6.

        -  Able to receive enteral nutrition through nasal/oral gastric or post-pyloric feeding
           tube.

      Exclusion:

        -  Planned heart or lung transplantation

        -  Planned cardiac surgery without cardiopulmonary bypass;

        -  Peri-operative support with extracorporeal membrane oxygenation (ECMO) or left
           ventricular assist device (LVAD).

      Study Protocol: Eligible patients will be identified during pre-operative assessment in the
      pre-operative clinic (PAC). All eligible patients or their surrogate decision-making/legal
      guardian will then be approached to obtain informed written consent.

      Each consenting participant will be randomly allocated (1:1) to receive post-operative
      enteral glutamine or identical placebo. Investigators, surgeons, intensivists, bedside nurses
      and participants will remain blinded to study allocation.

      Glutamine supplementation will be dosed at 0.5 g/kg satisfactory body weight (SBW)/day
      divided every 8 hours, starting 6 hours post-operatively and continued for 5 days. The dose
      of 0.5 g/kg SBW/day was effective in clinical studies using enteral glutamine in critically
      ill and/or burn injured and major trauma patients. The glutamine supplementation or placebo
      will be delivered via naso- or oro-gastric feeding tube after confirmation of placement by
      chest X-ray. For participants who are extubated prior to 5 days, enteral glutamine will be
      given by mouth for the duration of the 5 day period. Glutamine and placebo will be mixed in
      orange juice to maintain blinding.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Glutamine
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Proportion of Eligible Patients Providing Consent to Participate
time frame: Date of surgery until date of hospital discharge, an expected average of 2 weeks
description: Assess the FEASIBILITY of the protocol to (i) achieve >75% consent rate in eligible patients
measure: Acute Kidney Injury
time frame: Date of surgery until date of hospital discharge, an expected average of 2 weeks
measure: Duration of mechanical ventilation
time frame: Date of surgery until date of hospital discharge, an expected average of 2 weeks
measure: Duration of vasoactive support
time frame: Date of surgery until date of hospital discharge, an expected average of 2 weeks
measure: Blood transfusion
time frame: Date of surgery until date of hospital discharge, an expected average of 2 weeks
measure: Organ Dysfunction Score
time frame: Date of surgery until date of hospital discharge, an expected average of 2 weeks
description: Post-operative changes to the Sequential Organ Failure Assessment score
measure: Adverse events
time frame: Date of surgery until date of hospital discharge, an expected average of 2 weeks
description: Evaluate the SAFETY and ADVERSE EFFECTS of (i) enteral glutamine; and (ii) COMPLICATIONS from feeding tube placement, including: epistaxis, feeding tube malposition, pneumothorax, esophageal injury, gastric mucosal irritation, gastrointestinal bleeding, unplanned feeding tube removal, and need for feeding tube reinsertion
measure: Systemic inflammation
time frame: Date of surgery until the end of planned study intervention, expected 5-days
description: Systemic Inflammation/immunomodulation: We will evaluate for increases and changes in systemic inflammation stratified by study intervention. This will aid in providing proof-of-concept of the biologic plausibility of the study intervention. The investigators propose to evaluate serial measures of C-reactive protein (CRP), chemiluminescent endotoxin activity assay (EAA), and interleukin-6 (IL-6).
measure: Nosocomial infection
time frame: Date of surgery until date of hospital discharge, an expected average of 2 weeks
description: Nosocomial infections: The investigators will specifically examine for the following infections during the period of hospitalization after surgery: superficial and deep sternal wound infections; mediastinitis; saphenous vein graft harvest site wound infections; ventilator associated and hospital acquired pneumonia; urinary tract infections; bloodstream infections; catheter-related blood stream infections; and decubitus ulcers.
measure: Proportion of Randomized Patients Achieving Protocol Adherence
time frame: 5-days (date of surgery until the end of planned study intervention)
description: Obtain > 90% protocol adherence
measure: Mortality
time frame: From the Date of Surgery until Date of Death or 90-days, whichever occurs first
measure: Duration of ICU stay
time frame: Date of surgery until date of hospital discharge, an expected average of 2 weeks
measure: Duration of hospital stay
time frame: Date of surgery until date of hospital discharge, an expected average of 2 weeks
arm group label: Glutamine
arm group type: Experimental
description: Oral/enteral glutamine 0.5 g/kg satisfactory body weight per day (divided doses every 8 hours) starting 6 hours post-operatively
arm group label: Maltodextrin
arm group type: Placebo Comparator
description: Oral/enteral maltodextrin 0.5 g/kg satisfactory body weight per day (divided doses every 8 hours) starting 6 hours post-operatively
intervention type: Dietary Supplement
intervention name: Glutamine
description: Enteric L-Glutamine
arm group label: Glutamine
other name: L-Glutamine
intervention type: Dietary Supplement
intervention name: Maltodextrin
description: Enteric Maltodextrin
arm group label: Maltodextrin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sean Bagshaw
role: Principal Investigator
affiliation: University of Alberta
last name: Gurmeet Singh
role: Principal Investigator
affiliation: University of Alberta
facility: 
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Cross Infection