Glutamine to Improve Outcomes in Cardiac Surgery (GLADIATOR)

February 6, 2017 updated by: University of Alberta

GLutamine Enterally After carDiac Surgery for Inflammation Attenuation and ouTcOme impRovement (GLADIATOR): A Phase II Randomized, Blinded, Placebo-Controlled Trial

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 2B7
        • University of Alberta
      • Edmonton, Alberta, Canada, T6G2B7
        • Mazankowski Alberta Heart Institute, University of Alberta

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Consent (obtained pre-operatively)
  • Adult - aged 18 years or older;
  • Planned cardiovascular surgery with cardiopulmonary bypass;
  • Increased 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 Criteria:

  • Planned heart or lung transplantation
  • Planned cardiovascular surgery without cardiopulmonary bypass;
  • Peri-operative support with extracorporeal membrane oxygenation (ECMO) or left ventricular assist device (LVAD).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Glutamine
Oral/enteral glutamine 0.5 g/kg satisfactory body weight per day (divided doses every 8 hours) starting 6 hours post-operatively
Dietary supplement: Glutamine
Enteric L-Glutamine
Other Names:
  • L-Glutamine
Placebo Comparator: Maltodextrin
Oral/enteral maltodextrin 0.5 g/kg satisfactory body weight per day (divided doses every 8 hours) starting 6 hours post-operatively
Dietary supplement: Maltodextrin
Enteric Maltodextrin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of Eligible Patients Providing Consent to Participate
Time Frame: Date of surgery until date of hospital discharge, an expected average of 2 weeks
Assess the FEASIBILITY of the protocol to (i) achieve >75% consent rate in eligible patients
Date of surgery until date of hospital discharge, an expected average of 2 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Acute Kidney Injury
Time Frame: Date of surgery until date of hospital discharge, an expected average of 2 weeks
Date of surgery until date of hospital discharge, an expected average of 2 weeks
Duration of mechanical ventilation
Time Frame: Date of surgery until date of hospital discharge, an expected average of 2 weeks
Date of surgery until date of hospital discharge, an expected average of 2 weeks
Duration of vasoactive support
Time Frame: Date of surgery until date of hospital discharge, an expected average of 2 weeks
Date of surgery until date of hospital discharge, an expected average of 2 weeks
Blood transfusion
Time Frame: Date of surgery until date of hospital discharge, an expected average of 2 weeks
Date of surgery until date of hospital discharge, an expected average of 2 weeks
Organ Dysfunction Score
Time Frame: Date of surgery until date of hospital discharge, an expected average of 2 weeks
Post-operative changes to the Sequential Organ Failure Assessment score
Date of surgery until date of hospital discharge, an expected average of 2 weeks
Adverse events
Time Frame: Date of surgery until date of hospital discharge, an expected average of 2 weeks
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
Date of surgery until date of hospital discharge, an expected average of 2 weeks
Systemic inflammation
Time Frame: Date of surgery until the end of planned study intervention, expected 5-days
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).
Date of surgery until the end of planned study intervention, expected 5-days
Nosocomial infection
Time Frame: Date of surgery until date of hospital discharge, an expected average of 2 weeks
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.
Date of surgery until date of hospital discharge, an expected average of 2 weeks
Proportion of Randomized Patients Achieving Protocol Adherence
Time Frame: 5-days (date of surgery until the end of planned study intervention)
Obtain > 90% protocol adherence
5-days (date of surgery until the end of planned study intervention)

Other Outcome Measures

Outcome Measure
Time Frame
Mortality
Time Frame: From the Date of Surgery until Date of Death or 90-days, whichever occurs first
From the Date of Surgery until Date of Death or 90-days, whichever occurs first
Duration of ICU stay
Time Frame: Date of surgery until date of hospital discharge, an expected average of 2 weeks
Date of surgery until date of hospital discharge, an expected average of 2 weeks
Duration of hospital stay
Time Frame: Date of surgery until date of hospital discharge, an expected average of 2 weeks
Date of surgery until date of hospital discharge, an expected average of 2 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Alberta

Investigators

  • Principal Investigator: Sean Bagshaw, University of Alberta
  • Principal Investigator: Gurmeet Singh, University of Alberta

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2012

Primary Completion (Actual)

June 21, 2016

Study Completion (Actual)

June 21, 2016

Study Registration Dates

First Submitted

August 22, 2012

First Submitted That Met QC Criteria

October 9, 2012

First Posted (Estimate)

October 11, 2012

Study Record Updates

Last Update Posted (Estimate)

February 8, 2017

Last Update Submitted That Met QC Criteria

February 6, 2017

Last Verified

February 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MAZ_CVICU_001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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