Plain English Summary
Not provided at time of registration
Trial website
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 measure
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 (if study stopped)
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
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, IRSC
Funding Body Type
government organisation
Funding Body Subtype
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 Queens 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
Basic results (scientific)
See https://clinicaltrials.gov/ct2/show/results/NCT00133978
Publication list
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
-
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.
-
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.