Trial of Glutamine and Antioxidant Supplementation in Critically Ill Patients

Not Applicable

Completed

Conditions: Critical Illness
Sepsis
Multiple Organ Failure

Interventions: Other: Glutamine + Antioxidants
Other: Glutamine
Other: Antioxidants
Other: Placebo

Registration Number: NCT00133978

Lead Sponsor: Daren K. Heyland

Brief Summary: The purpose of this study is to determine whether providing high dose glutamine and antioxidants to critically ill patients will be associated with improved survival.

Detailed Description: Background:

Critically ill patients experience a degree of hyperinflammation, cellular immune dysfunction, and oxidative stress. Supplementation with key nutrients, like glutamine and antioxidants, is most likely to have a favourable effect on these physiological parameters leading to an improvement in clinical outcomes. The results of two separate meta-analyses suggested that glutamine and antioxidants may be associated with improved survival. We have recently completed a dosing study to determine the maximal tolerable dose (MTD) of glutamine dipeptides and antioxidants in critically ill patients with evidence of hypoperfusion. The purpose of this protocol is to evaluate the effect of high dose glutamine and antioxidant supplementation on mortality in a large scale randomized trial.

Study Intervention:

Patients will be randomized to receive glutamine supplementation or antioxidant supplementation (or respective placebo).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1223

Inclusion Criteria

Mechanically ventilated patients > or = 18 years old
2 or more organ failures related to acute illness

Exclusion Criteria

> 24 hours from admission to ICU
Patients who are moribund
Lack of commitment to aggressive care
Absolute contraindication to enteral nutrients
Severe acquired brain injury
Routine elective cardiac surgery
Primary admission of burns > 30% body surface area
Weight < 50 kgms or > 200 kgms
Pregnant or lactating patients
Previous randomization in this study
Enrollment in a related ICU interventional study
Child's class C liver disease
Metastatic cancer with life expectancy < 6 months
Seizure disorder requiring anticonvulsant medication

Study & Design

Study Type: INTERVENTIONAL

Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Glutamine + Antioxidants	Glutamine + Antioxidants	Glutamine and antioxidant supplementation
Glutamine	Glutamine	Glutamine supplementation
Antioxidants	Antioxidants	Antioxidant supplementation
Placebo	Placebo	Non-isonitrogenic, iso-caloric placebo solution

Primary Outcome Measures

Name	Time	Method
28-day Mortality	Day 28	28-day mortality/status: at 28 days after randomization;

Secondary Outcome Measures

Name	Time	Method
ICU Length of Stay	Day 28	Measure of the duration of participant stay in the ICU
Hospital Length of Stay	6 months (from ICU admission)	Measure of the duration of the participant's hospital stay
ICU Acquired Infection	Day 28	We have made some modifications the definitions developed by the International Sepsis Forum Consensus Conference (CCM 2005;33:1538-1548) to operationalize the adjudication of infections in this trial. We grade the certainty of the diagnosis of infection using definitions for 'Definite', 'Probable', and 'Possible' for each category of infection. The categories of infection are: Deep surgical wound infection, Incisional (or superficial) surgical wound infection, Skin and soft-tissue infection (non-surgical) (SSTS), Catheter-related blood stream infections (CRI), Primary blood stream infections (BSI), Lower urinary tract infection, Upper urinary tract infection, Intra abdominal infection, Sinusitis, Lower respiratory tract infection (excluding pneumonia), ICU Acquired Pneumonia and Other.

Trial Locations

Locations (34): Royal Alexandra Hospital
🇨🇦
Edmonton, Alberta, Canada
Montreal General
🇨🇦
Montreal, Quebec, Canada
St Paul's Hospital
🇨🇦
Vancouver, British Columbia, Canada
Royal Jubilee Hospital
🇨🇦
Victoria, British Columbia, Canada
Victoria General Hospital
🇨🇦
Victoria, British Columbia, Canada
Sunnybrook & Women's College, Toronto
🇨🇦
Toronto, Ontario, Canada
Hopital Maisonneuve-Rosemount
🇨🇦
Montreal, Quebec, Canada
Miami Valley Hospital
🇺🇸
Dayton, Ohio, United States
Univ. of Colorado at Denver and Health Sciences Center
🇺🇸
Aurora, Colorado, United States
University of Texas
🇺🇸
Houston, Texas, United States
University of Louisville
🇺🇸
Louisville, Kentucky, United States
UZ Brussels
🇧🇪
Brussels, Belgium
Fletcher Allan Centre
🇺🇸
Burlington, Vermont, United States
University Hospital
🇧🇪
Liege, Belgium
Grey Nun's Hospital, Edmonton
🇨🇦
Edmonton, Alberta, Canada
Vancouver Hospital
🇨🇦
Vancouver, British Columbia, Canada
St. Boniface General Hospital
🇨🇦
Winnipeg, Manitoba, Canada
Health Science Centre
🇨🇦
Winnipeg, Manitoba, Canada
St Joseph's Healthcare
🇨🇦
Hamilton, Ontario, Canada
Capital Health Queen Elizabeth II HSC
🇨🇦
Halifax, Nova Scotia, Canada
London HSC Victoria Campus, ON
🇨🇦
London, Ontario, Canada
Kingston General Hospital
🇨🇦
Kingston, Ontario, Canada
Ottawa Hospital
🇨🇦
Ottawa, Ontario, Canada
Ottawa Hospital Civic Hospital
🇨🇦
Ottawa, Ontario, Canada
Mt Sinai Hospital
🇨🇦
Toronto, Ontario, Canada
Royal Victoria Hospital
🇨🇦
Montreal, Quebec, Canada
Hopital de Sacre-Coeur
🇨🇦
Montreal, Quebec, Canada
Enfant-Jesus
🇨🇦
Quebec, Canada
Universitatsklinikum der Ernst-Moritz-Arndt-Universitat
🇩🇪
Greifswald, Germany
Asklepios Kliniken Hamburg Altona
🇩🇪
Hamburg, Germany
University Medical Center Schleswig-Holstein
🇩🇪
Kiel, Germany
CHUV
🇨🇭
Lausanne, Switzerland
University of Zurich
🇨🇭
Zurich, Switzerland
Universitatsklinikum Schleswig-Holstein Campus Luebeck
🇩🇪
Lubeck, Germany