GLADIATOR: Glutamine to Improve Outcomes in Cardiac Surgery

Sponsor

University of Alberta (Other)

Overall Status

Completed

CT.gov ID

NCT01704430

Collaborator

(none)

Enrollment

Locations

Arms

45.6

Duration (Months)

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Nosocomial Infection	Dietary Supplement: Glutamine Dietary Supplement: Maltodextrin	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

GlutamineGlutamine

Masking:

Quadruple (Participant, Care Provider, 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

Study Start Date :

Sep 1, 2012

Actual Primary Completion Date :

Jun 21, 2016

Actual Study Completion Date :

Jun 21, 2016

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Proportion of Eligible Patients Providing Consent to Participate [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

Secondary Outcome Measures

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

Other Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).