Glutamine to Improve Outcomes in Cardiac Surgery (GLADIATOR)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2012 by University of Alberta
Sponsor:
Information provided by (Responsible Party):
University of Alberta
ClinicalTrials.gov Identifier:
NCT01704430
First received: August 22, 2012
Last updated: October 9, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Nosocomial Infection
Dietary Supplement: Glutamine
Dietary Supplement: Maltodextrin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: GLutamine Enterally After carDiac Surgery for Inflammation Attenuation and ouTcOme impRovement (GLADIATOR): A Phase II Randomized, Blinded, Placebo-Controlled Trial

Resource links provided by NLM:


Further study details as provided by University of Alberta:

Primary Outcome Measures:
  • Proportion of Eligible Patients Providing Consent to Participate [ Time Frame: Date of surgery until date of hospital discharge, an expected average of 2 weeks ] [ Designated as safety issue: No ]
    Assess the FEASIBILITY of the protocol to (i) achieve >75% consent rate in eligible patients


Secondary Outcome Measures:
  • Acute Kidney Injury [ Time Frame: Date of surgery until date of hospital discharge, an expected average of 2 weeks ] [ Designated as safety issue: No ]
  • Duration of mechanical ventilation [ Time Frame: Date of surgery until date of hospital discharge, an expected average of 2 weeks ] [ Designated as safety issue: No ]
  • Duration of vasoactive support [ Time Frame: Date of surgery until date of hospital discharge, an expected average of 2 weeks ] [ Designated as safety issue: No ]
  • Blood transfusion [ Time Frame: Date of surgery until date of hospital discharge, an expected average of 2 weeks ] [ Designated as safety issue: No ]
  • Organ Dysfunction Score [ Time Frame: Date of surgery until date of hospital discharge, an expected average of 2 weeks ] [ Designated as safety issue: No ]
    Post-operative changes to the Sequential Organ Failure Assessment score

  • Adverse events [ Time Frame: Date of surgery until date of hospital discharge, an expected average of 2 weeks ] [ Designated as safety issue: Yes ]
    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

  • Systemic inflammation [ Time Frame: Date of surgery until the end of planned study intervention, expected 5-days ] [ Designated as safety issue: No ]
    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).

  • Nosocomial infection [ Time Frame: Date of surgery until date of hospital discharge, an expected average of 2 weeks ] [ Designated as safety issue: No ]
    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.

  • Proportion of Randomized Patients Achieving Protocol Adherence [ Time Frame: 5-days (date of surgery until the end of planned study intervention) ] [ Designated as safety issue: No ]
    Obtain > 90% protocol adherence


Other Outcome Measures:
  • Mortality [ Time Frame: From the Date of Surgery until Date of Death or 90-days, whichever occurs first ] [ Designated as safety issue: No ]
  • Duration of ICU stay [ Time Frame: Date of surgery until date of hospital discharge, an expected average of 2 weeks ] [ Designated as safety issue: No ]
  • Duration of hospital stay [ Time Frame: Date of surgery until date of hospital discharge, an expected average of 2 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: September 2012
Estimated Study Completion Date: August 2013
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01704430

Contacts
Contact: Sean M Bagshaw bagshaw@ualberta.ca
Contact: Gurmeet Singh gurmeet.singh@me.com

Locations
Canada, Alberta
Mazankowski Alberta Heart Institute, University of Alberta Recruiting
Edmonton, Alberta, Canada, T6G2B7
Contact: Kristen Reid    780-407-7448    Kristen.Reid@albertahealthservices.ca   
Contact: Samantha Taylor    780-407-7448    Samantha.Taylor@albertahealthservices.ca   
Principal Investigator: Sean M Bagshaw         
Principal Investigator: Gurmeet Singh         
Sub-Investigator: Steven Meyer         
Sub-Investigator: Rachel Khadaroo         
Sub-Investigator: David Ross         
Sub-Investigator: Mohamad Zibdawi         
Sub-Investigator: Ross Tsuyuki         
University of Alberta Recruiting
Edmonton, Alberta, Canada, T6G 2B7
Contact: Sean M Bagshaw, MD, MSc    780-407-7448    bagshaw@ualberta.ca   
Contact: Kristen Reid    780-407-7448    kristen.reid@albertahealthservices.ca   
Principal Investigator: Sean M Bagshaw         
Principal Investigator: Gurmeet Singh         
Sponsors and Collaborators
University of Alberta
Investigators
Principal Investigator: Sean Bagshaw University of Alberta
Principal Investigator: Gurmeet Singh University of Alberta
  More Information

No publications provided

Responsible Party: University of Alberta
ClinicalTrials.gov Identifier: NCT01704430     History of Changes
Other Study ID Numbers: MAZ_CVICU_001
Study First Received: August 22, 2012
Last Updated: October 9, 2012
Health Authority: Canada: Health Canada

Keywords provided by University of Alberta:
Cardiac surgery
Cardiac bypass
Intensive Care
Nosocomial infection
Glutamine
Randomized trial

Additional relevant MeSH terms:
Cross Infection
Infection

ClinicalTrials.gov processed this record on July 09, 2014