Clinical trial NCT01704430: Glutamine to Improve Outcomes in Cardiac Surgery
Official title: GLutamine Enterally After carDiac Surgery for Inflammation Attenuation and ouTcOme impRovement (GLADIATOR): A Phase II Randomized, Blinded, Placebo-Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Nosocomial Infection
Keywords: Cardiac surgery
Cardiac bypass
Intensive Care
Nosocomial infection
Glutamine
Randomized trial
Lead sponsor: University of Alberta
Sponsor class: OTHER
First posted: 2012-10-11
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Glutamine
Primary purpose: PREVENTION

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.

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 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).

Primary outcomes:
measure: Proportion of Eligible Patients Providing Consent to Participate
timeFrame: Date of surgery until date of hospital discharge, an expected average of 2 weeks
Secondary outcomes:
measure: Acute Kidney Injury
timeFrame: Date of surgery until date of hospital discharge, an expected average of 2 weeks
measure: Duration of mechanical ventilation
timeFrame: Date of surgery until date of hospital discharge, an expected average of 2 weeks
measure: Duration of vasoactive support
timeFrame: Date of surgery until date of hospital discharge, an expected average of 2 weeks
measure: Blood transfusion
timeFrame: Date of surgery until date of hospital discharge, an expected average of 2 weeks
measure: Organ Dysfunction Score
timeFrame: Date of surgery until date of hospital discharge, an expected average of 2 weeks
measure: Adverse events
timeFrame: Date of surgery until date of hospital discharge, an expected average of 2 weeks
measure: Systemic inflammation
timeFrame: Date of surgery until the end of planned study intervention, expected 5-days
measure: Nosocomial infection
timeFrame: Date of surgery until date of hospital discharge, an expected average of 2 weeks
measure: Proportion of Randomized Patients Achieving Protocol Adherence
timeFrame: 5-days (date of surgery until the end of planned study intervention)
Other outcomes:
measure: Mortality
timeFrame: From the Date of Surgery until Date of Death or 90-days, whichever occurs first
measure: Duration of ICU stay
timeFrame: Date of surgery until date of hospital discharge, an expected average of 2 weeks
measure: Duration of hospital stay
timeFrame: Date of surgery until date of hospital discharge, an expected average of 2 weeks
Locations:
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Edmonton
country: Canada
facility: Mazankowski Alberta Heart Institute, University of Alberta
state: Alberta
Study officials:
affiliation: University of Alberta
name: Sean Bagshaw
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alberta
name: Gurmeet Singh
role: PRINCIPAL_INVESTIGATOR
References: