Clinical trial NCT00133978: Trial of Glutamine and Antioxidant Supplementation in Critically Ill Patients
Official title: REducing Deaths Due to OXidative Stress The REDOXS© Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Critical Illness
Sepsis
Multiple Organ Failure
Keywords: randomized trial
antioxidants
glutamine
organ failure
Lead sponsor: Clinical Evaluation Research Unit at Kingston General Hospital
Sponsor class: OTHER
Collaborators: name: Fresenius Kabi
First posted: 2005-08-24
Enrollment: 1223
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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).

Eligibility criteria: 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

Primary outcomes:
measure: 28-day Mortality
timeFrame: Day 28
Secondary outcomes:
measure: ICU Length of Stay
timeFrame: Day 28
measure: ICU Acquired Infection
timeFrame: Day 28
measure: Hospital Length of Stay
timeFrame: 6 months (from ICU admission)
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Univ. of Colorado at Denver and Health Sciences Center
state: Colorado
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Dayton
country: United States
facility: Miami Valley Hospital
state: Ohio
city: Houston
country: United States
facility: University of Texas
state: Texas
city: Burlington
country: United States
facility: Fletcher Allan Centre
state: Vermont
city: Brussels
country: Belgium
facility: UZ Brussels
city: Liege
country: Belgium
facility: University Hospital
city: Edmonton
country: Canada
facility: Royal Alexandra Hospital
state: Alberta
city: Edmonton
country: Canada
facility: Grey Nun's Hospital, Edmonton
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: St Paul's Hospital
state: British Columbia
city: Victoria
country: Canada
facility: Royal Jubilee Hospital
state: British Columbia
city: Victoria
country: Canada
facility: Victoria General Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: St. Boniface General Hospital
state: Manitoba
city: Winnipeg
country: Canada
facility: Health Science Centre
state: Manitoba
city: Halifax
country: Canada
facility: Capital Health Queen Elizabeth II HSC
state: Nova Scotia
city: Hamilton
country: Canada
facility: St Joseph's Healthcare
state: Ontario
city: Kingston
country: Canada
facility: Kingston General Hospital
state: Ontario
city: London
country: Canada
facility: London HSC Victoria Campus, ON
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Civic Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook & Women's College, Toronto
state: Ontario
city: Toronto
country: Canada
facility: Mt Sinai Hospital
state: Ontario
city: Montreal
country: Canada
facility: Hopital Maisonneuve-Rosemount
state: Quebec
city: Montreal
country: Canada
facility: Royal Victoria Hospital
state: Quebec
city: Montreal
country: Canada
facility: Montreal General
state: Quebec
city: Montreal
country: Canada
facility: Hopital de Sacre-Coeur
state: Quebec
city: Quebec
country: Canada
facility: Enfant-Jesus
city: Greifswald
country: Germany
facility: Universitatsklinikum der Ernst-Moritz-Arndt-Universitat
city: Hamburg
country: Germany
facility: Asklepios Kliniken Hamburg Altona
city: Kiel
country: Germany
facility: University Medical Center Schleswig-Holstein
city: Lubeck
country: Germany
facility: Universitatsklinikum Schleswig-Holstein Campus Luebeck
city: Lausanne
country: Switzerland
facility: CHUV
city: Zurich
country: Switzerland
facility: University of Zurich
Study officials:
affiliation: Clinical Evaluation Research Unit, Kingston General Hospital
name: Daren Heyland, MD
role: STUDY_CHAIR
References:
citation: Heyland DK, Dhaliwal R, Drover JW, Gramlich L, Dodek P; Canadian Critical Care Clinical Practice Guidelines Committee. Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients. JPEN J Parenter Enteral Nutr. 2003 Sep-Oct;27(5):355-73. doi: 10.1177/0148607103027005355.
citation: Heyland DK, Dhaliwal R, Suchner U, Berger MM. Antioxidant nutrients: a systematic review of trace elements and vitamins in the critically ill patient. Intensive Care Med. 2005 Mar;31(3):327-37. doi: 10.1007/s00134-004-2522-z. Epub 2004 Dec 17.
citation: Novak F, Heyland DK, Avenell A, Drover JW, Su X. Glutamine supplementation in serious illness: a systematic review of the evidence. Crit Care Med. 2002 Sep;30(9):2022-9. doi: 10.1097/00003246-200209000-00011.
citation: Heyland D, Muscedere J, Wischmeyer PE, Cook D, Jones G, Albert M, Elke G, Berger MM, Day AG; Canadian Critical Care Trials Group. A randomized trial of glutamine and antioxidants in critically ill patients. N Engl J Med. 2013 Apr 18;368(16):1489-97. doi: 10.1056/NEJMoa1212722.
citation: Heyland DK, Elke G, Cook D, Berger MM, Wischmeyer PE, Albert M, Muscedere J, Jones G, Day AG; Canadian Critical Care Trials Group. Glutamine and antioxidants in the critically ill patient: a post hoc analysis of a large-scale randomized trial. JPEN J Parenter Enteral Nutr. 2015 May;39(4):401-9. doi: 10.1177/0148607114529994. Epub 2014 May 5.