Glutamine to Improve Outcomes in Cardiac Surgery

Nosocomial Infection Clinical Trial

— GLADIATOR  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01704430
• Other study ID #: MAZ_CVICU_001
• Status: Completed
• Phase: N/A
• First received: August 22, 2012
• Last updated: February 6, 2017
• Start date: September 2012
• Est. completion date: June 21, 2016

Study information

• Verified date: February 2017
• Source: University of Alberta
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: June 21, 2016
• Est. primary completion date: June 21, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Cross Infection
• Nosocomial Infection

Intervention

Dietary Supplement:
• Glutamine
Enteric L-Glutamine
• Maltodextrin
Enteric Maltodextrin

Locations

Country	Name	City	State
Canada	Mazankowski Alberta Heart Institute, University of Alberta	Edmonton	Alberta
Canada	University of Alberta	Edmonton	Alberta

Sponsors (1)

Lead Sponsor	Collaborator
University of Alberta

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Mortality		From the Date of Surgery until Date of Death or 90-days, whichever occurs first
Other	Duration of ICU stay		Date of surgery until date of hospital discharge, an expected average of 2 weeks
Other	Duration of hospital stay		Date of surgery until date of hospital discharge, an expected average of 2 weeks
Primary	Proportion of Eligible Patients Providing Consent to Participate	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	Acute Kidney Injury		Date of surgery until date of hospital discharge, an expected average of 2 weeks
Secondary	Duration of mechanical ventilation		Date of surgery until date of hospital discharge, an expected average of 2 weeks
Secondary	Duration of vasoactive support		Date of surgery until date of hospital discharge, an expected average of 2 weeks
Secondary	Blood transfusion		Date of surgery until date of hospital discharge, an expected average of 2 weeks
Secondary	Organ Dysfunction Score	Post-operative changes to the Sequential Organ Failure Assessment score	Date of surgery until date of hospital discharge, an expected average of 2 weeks
Secondary	Adverse events	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
Secondary	Systemic inflammation	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
Secondary	Nosocomial infection	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
Secondary	Proportion of Randomized Patients Achieving Protocol Adherence	Obtain > 90% protocol adherence	5-days (date of surgery until the end of planned study intervention)