Trial of Glutamine and Antioxidant Supplementation in Critically Ill Patients

Sepsis Clinical Trial

— REDOXS  

Official title:

REducing Deaths Due to OXidative Stress The REDOXS© Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00133978
• Other study ID #: REDOXS
• Secondary ID: EudraCT-No: 2007
• Status: Completed
• Phase: N/A
• Start date: April 2005
• Est. completion date: May 2012

Study information

• Verified date: December 2020
• Source: Clinical Evaluation Research Unit at Kingston General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 1223
• Est. completion date: May 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Critical Illness
• Multiple Organ Failure
• Sepsis

Intervention

Other:
• Glutamine
0.35 gm/kg/day parenterally and 30 gms/day enterally
• Antioxidants
500 micrograms of selenium/day parenterally and selenium 300 microgram, zinc 20 mg, beta carotene 10 mg, vitamine E 500 mg and vitamin C 1500 mg per day enterally
• Glutamine + Antioxidants
0.35 g/kg/day glutamine parenterally and 30 g/day of glutamine enterally. 500 mcg selenium parenterally plus the following administered enterally: selenium 300 mcg, zing 20 mg, beta-carotene 10 mg, vitamin E 500 mg and vitamin C 1500mg
• Placebo
Normal saline intravenously and EN placebo formula (from Fresenius Kabi, Germany)

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Daren K. Heyland	Fresenius Kabi

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Germany,  Switzerland, 

References & Publications (4)

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: — View 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. — View 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. Epub 2004 Dec 17. Review. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	28-day Mortality	28-day mortality/status: at 28 days after randomization;	Day 28
Secondary	ICU Length of Stay	Measure of the duration of participant stay in the ICU	Day 28
Secondary	ICU Acquired Infection	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.	Day 28
Secondary	Hospital Length of Stay	Measure of the duration of the participant's hospital stay	6 months (from ICU admission)

External Links

•   Click here for more information about this study: A Randomized Trial of Glutamine and Antioxidant Supplementation in Critically Ill Patients