Condition category
Signs and Symptoms
Date applied
27/12/2006
Date assigned
27/12/2006
Last edited
22/03/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

http://www.criticalcarenutrition.com/redoxs

Contact information

Type

Scientific

Primary contact

Dr Daren Keith Heyland

ORCID ID

Contact details

Clinical Evaluation Research Unit
Angada 4
Kingston General Hospital
Kingston
K7L 2V7
Canada
+1 (0)613 549 6666 ext 3339
dkh2@queensu.ca

Type

Public

Additional contact

Dr Rupinder Dhaliwal

ORCID ID

Contact details

Clinical Evaluation Research Unit (CERU)
Angada 4
Kingston General Hospital
Kingston
K7L 2V7
Canada
+1 (0)613 549 6666 ext 3830
dhaliwar@KGH.KARI.NET

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT00133978

Protocol/serial number

MCT-82214

Study information

Scientific title

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

Acronym

REDOXS©

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

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Can be found at http://www.criticalcarenutrition.com/index.php?option=com_content&task=view&id=19&Itemid=42

Condition

Severe organ dysfunction/critical illness

Intervention

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

Supplement

Phase

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

01/01/2007

Overall trial end date

31/01/2010

Reason abandoned

Eligibility

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

Patient

Age group

Adult

Gender

Both

Target number of participants

1200

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

01/01/2007

Recruitment end date

31/01/2010

Locations

Countries of recruitment

Canada

Trial participating centre

Kingston General Hospital
Kingston
K7L 2V7
Canada

Sponsor information

Organisation

Queen's University (Canada)

Sponsor details

Rideau Building
Kingston
Ontario
K7L 3N6
Canada
+1 (0)613 533 2050
gerrondg@post.queensu.ca

Sponsor type

University/education

Website

http://www.queensu.ca/

Funders

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

Location

Canada

Funder name

Fresenius-Kabi (Germany)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Clinical Teachers Association of Queen’s University (Canada)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

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

See https://clinicaltrials.gov/ct2/show/results/NCT00133978

Publication summary

2006 rationale and study design in: http://www.ncbi.nlm.nih.gov/pubmed/16923310
2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/23594003

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.