REducing Deaths due to OXidative Stress: the REDOXS© Study

ISRCTN	ISRCTN48486094
DOI	https://doi.org/10.1186/ISRCTN48486094
ClinicalTrials.gov number	NCT00133978
Secondary identifying numbers	MCT-82214

Submission date: 27/12/2006
Registration date: 27/12/2006
Last edited: 22/03/2016

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Signs and Symptoms

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Study website

Contact information

Dr Daren Keith Heyland
Scientific

Clinical Evaluation Research Unit
Angada 4
Kingston General Hospital
Kingston
K7L 2V7
Canada

Phone	+1 (0)613 549 6666 ext 3339
Email	dkh2@queensu.ca

Dr Rupinder Dhaliwal
Public

Clinical Evaluation Research Unit (CERU)
Angada 4
Kingston General Hospital
Kingston
K7L 2V7
Canada

Phone	+1 (0)613 549 6666 ext 3830
Email	dhaliwar@KGH.KARI.NET

Study information

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
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Can be found at http://www.criticalcarenutrition.com/index.php?option=com_content&task=view&id=19&Itemid=42
Scientific title	REducing Deaths due to OXidative Stress: a randomised trial of glutamine and anti-oxidant supplementation in critically ill patients
Study acronym	REDOXS©
Study objectives	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(s)	Research Ethics Board of Queen's University Health Sciences and Affilated Teaching Hospitals (Canada), 22/03/2006
Health condition(s) or problem(s) studied	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
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 study start date	01/01/2007
Completion date	31/01/2010

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	1200
Key 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
Key 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
Date of first enrolment	01/01/2007
Date of final enrolment	31/01/2010

Locations

Countries of recruitment

Canada

Study participating centre

Kingston General Hospital

Kingston
K7L 2V7
Canada

Sponsor information

Queen's University (Canada)
University/education

Rideau Building
Kingston
Ontario
K7L 3N6
Canada

Phone	+1 (0)613 533 2050
Email	gerrondg@post.queensu.ca
Website	http://www.queensu.ca/
"ROR"	https://ror.org/02y72wh86

Funders

Funder type

Research organisation

Canadian Institutes of Health Research (ref: MCT-82214)
Government organisation / National government

Alternative name(s): Instituts de Recherche en Santé du Canada, Canadian Institutes of Health Research (CIHR), CIHR_IRSC, Canadian Institutes of Health Research | Ottawa ON, CIHR, IRSC
Location: Canada

Fresenius-Kabi (Germany)

No information available

Clinical Teachers Association of Queens University (Canada)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Peer reviewed?	Patient-facing?
Basic results			No	No
Other publications	rationale and study design	01/08/2006	Yes	No
Results article	results	18/04/2013	Yes	No

Editorial Notes

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