Condition category
Signs and Symptoms
Date applied
Date assigned
Last edited
Prospectively registered
Overall trial status
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information



Primary contact

Dr Daren Keith Heyland


Contact details

Clinical Evaluation Research Unit
Angada 4
Kingston General Hospital
K7L 2V7
+1 (0)613 549 6666 ext 3339



Additional contact

Dr Rupinder Dhaliwal


Contact details

Clinical Evaluation Research Unit (CERU)
Angada 4
Kingston General Hospital
K7L 2V7
+1 (0)613 549 6666 ext 3830

Additional identifiers

EudraCT number number


Protocol/serial number


Study information

Scientific title

REducing Deaths due to OXidative Stress: a randomised trial of glutamine and anti-oxidant supplementation in critically ill patients



Study hypothesis

Primary hypothesis:
Glutamine and antioxidant supplementation improves the survival of critically ill patients or reduces 28 day mortality.

Secondary hypothesis:
Glutamine and antioxidant supplementation will have a favourable effect on duration of mechanical ventilation, stay in Intensive Care Unit (ICU) and hospital, development of infectious complications, multiple organ dysfunction, antibiotic use, mitochondrial function and quality of life.

Ethics approval

Research Ethics Board of Queen's University Health Sciences and Affilated Teaching Hospitals (Canada), 22/03/2006

Study design

Multicentre non-pharmaceutical randomised factorial 2x2 design, placebo trial with study participants, investigator, caregiver, study nurses gathering data, outcome assessor, and data analyst blinded.

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet

Can be found at


Severe organ dysfunction/critical illness


1. Glutamine: 0.35 g/kg/day glutamine parenterally and 30 g/day enterally for a maximum of 28 days
2. Antioxidants: 500 µg of selenium/day parenterally and selenium 300 µg, zinc 20 mg, beta carotene 10 mg, vitamin E 500 mg, and vitamin C 1500 mg per day enterally for a maximum of 28 days
3. Glutamine and Antioxidants: Combination of glutamine and antioxidant treatments once daily for a maximum of 28 days
4. Placebo: normal saline parenterally and matching enteral placebo for a maximum of 28 days

Intervention type



Not Specified

Drug names

Glutamine and antioxidant supplementation

Primary outcome measures

Mortality at 28th day

Secondary outcome measures

1. Duration of mechanical ventilation, end of ICU stay
2. Stay in ICU and hospital, end of ICU and hospital stay
3. Development of infectious complications, throughout ICU stay
4. Multiple organ dysfunction, throughout ICU stay
5. Antibiotic use, throughout ICU stay
6. Mitochondrial function, throughout ICU stay
7. 36-item Short Form health survey (SF-36), quality of life survey, at three months and six months from ICU admission

Overall trial start date


Overall trial end date


Reason abandoned


Participant inclusion criteria

1. Mechanically ventilated adult patients (more than or equal to 18 years old, either sex) admitted to ICU
2. Two or more of the following organ failures related to their acute illness:
2.1. A Partial Pressure of Oxygen in Arterial Blood (PaO2)/Fraction of Inspired Oxygen (FiO2) ratio of less than or equal to 300
2.2. Clinical evidence of hypoperfusion defined as the need for vasopressor agents (norepinephrine, epinephrine, vasopressin, more than or equal to 5 µg/kg/min of dopamine, or more than or equal to 50 µg/min phenylephrine) for greater than or equal to two hours
2.3. In patients without known renal disease, renal dysfunction defined as a serum creatinine more than or equal to 171 µmol/L or a urine output of less than 500 ml/last 24 hours (or 80 ml/last four hours if a 24 hour period of observation not available). In patients with acute on chronic renal failure (pre-dialysis), an absolute increase of more than or equal to 80 µmol/L from baseline or pre-admission creatinine or a urine output of less than 500 ml/last 24 hours (or 80 ml/last four hours) will be required
2.4. A platelet count of less than 50 x 10^9/L

Participant type


Age group




Target number of participants


Participant exclusion criteria

1. More than 24 hours from admission to ICU
2. Patients who are moribund (not expected to be in ICU for more than 48 hours due to imminent death)
3. A lack of commitment to full aggressive care (anticipated withholding or withdrawing treatments in the first week)
4. Absolute contraindication to enteral nutrients (e.g., Gastro-Intestinal (GI) perforation, obstruction or no GI tract access for any reason)
5. Patients with severe acquired brain injury:
5.1. Significant head trauma (defined as an injury, in the opinion of the investigator, that represents a severe, disabling, or fatal brain injury)
5.2. Grade four or five subarachnoid haemorrhage
5.3. Stroke resulting in coma and intubation
5.4. Post-cardiac arrest with suspected significant anoxic brain injury
6. Seizure disorder requiring anticonvulsant medication
7. Cirrhosis - Child's class C liver disease
8. Metastatic cancer or Stage IV Lymphoma with life expectancy less than six months
9. Routine elective cardiac surgery (patients with complicated peri-operative course requiring pressors, Intra-Aortic Balloon Pump (IABP), ventricular assist devices can be included)
10. Patients with primary admission diagnosis of burns (more than or equal to 30% Body Surface Area [BSA])
11. Weight less than 50 kg or greater than 200 kg
12. Pregnant patients or lactating with the intent to breastfeed
13. Previous randomisation in this study
14. Enrolment in a related ICU interventional study

Recruitment start date


Recruitment end date



Countries of recruitment


Trial participating centre

Kingston General Hospital
K7L 2V7

Sponsor information


Queen's University (Canada)

Sponsor details

Rideau Building
K7L 3N6
+1 (0)613 533 2050

Sponsor type




Funder type

Research organisation

Funder name

Canadian Institutes of Health Research (ref: MCT-82214)

Alternative name(s)

Instituts de Recherche en Santé du Canada, CIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government



Funder name

Fresenius-Kabi (Germany)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Funder name

Clinical Teachers Association of Queen’s University (Canada)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting


Publication summary

2006 rationale and study design in:
2013 results in:

Publication citations

  1. Rationale and study design

    Heyland DK, Dhaliwal R, Day AG, Muscedere J, Drover J, Suchner U, Cook D, , REducing Deaths due to OXidative Stress (The REDOXS Study): Rationale and study design for a randomized trial of glutamine and antioxidant supplementation in critically-ill patients., Proc Nutr Soc, 2006, 65, 3, 250-263.

  2. Results

    Heyland D1, 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, 368, 16, 1489-1497, doi: 10.1056/NEJMoa1212722.

Additional files

Editorial Notes

22/03/2016: added link to results - basic reporting.