Critical IllnessREDOXSNCT00133978
Trial of Glutamine and Antioxidant Supplementation in Critically Ill Patients
A study testing Glutamine, Antioxidants and Glutamine + Antioxidants in people with Critical Illness and Sepsis, run by Daren K. Heyland at 34 sites in 5 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Critical Illness, Sepsis, Multiple Organ Failure
- What is being tested?
- Glutamine, Antioxidants and Glutamine + Antioxidants
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,223 participants
- Where
- 34 sitesin 5 countries
- Study dates
- Apr 2005to May 2012
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Mechanically ventilated patients > or = 18 years old
- 2 or more organ failures related to acute illness
Who cannot join
- > 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
Show all 14Show fewer
- 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
Trial locations and contacts
34 sites in 5 countries.
34 sites in 5 countries
Canada21 sites
Royal Alexandra Hospital
Edmonton, Alberta, T5H 3V9
Grey Nun's Hospital, Edmonton
Edmonton, Alberta, T6L 5X8
Capital Health Queen Elizabeth II HSC
Halifax, Nova Scotia, B3H 2Y9
St Joseph's Healthcare
Hamilton, Ontario, L8N 4A6
Kingston General Hospital
Kingston, Ontario, K7L 2V7
London HSC Victoria Campus, ON
London, Ontario, N6A 5W9
Hopital Maisonneuve-Rosemount
Montreal, Quebec, H1T 2M4
Royal Victoria Hospital
Montreal, Quebec, H3A 1A1
Montreal General
Montreal, Quebec, H3G 1A4
Hopital de Sacre-Coeur
Montreal, Quebec, H4J 1C5
Ottawa Hospital
Ottawa, Ontario, K1H 8H6
Ottawa Hospital Civic Hospital
Ottawa, Ontario, K1Y 4E9
Enfant-Jesus
Québec, G1J 1Z4
Sunnybrook & Women's College, Toronto
Toronto, Ontario, M4N 3M5
Mt Sinai Hospital
Toronto, Ontario, M5G 1X5
Vancouver Hospital
Vancouver, British Columbia, V5Z 1C6
St Paul's Hospital
Vancouver, British Columbia, V6Z 1Y6
Royal Jubilee Hospital
Victoria, British Columbia, V8R 1J8
Victoria General Hospital
Victoria, British Columbia, V8Z 6R5
St. Boniface General Hospital
Winnipeg, Manitoba, R2H 2A6
Health Science Centre
Winnipeg, Manitoba, R3A 1R9
United States5 sites
Univ. of Colorado at Denver and Health Sciences Center
Aurora, Colorado, 80045
Fletcher Allan Centre
Burlington, Vermont, 05401
Miami Valley Hospital
Dayton, Ohio, 45409
University of Texas
Houston, Texas, 6431
University of Louisville
Louisville, Kentucky, 40202
Germany4 sites
Universitatsklinikum der Ernst-Moritz-Arndt-Universitat
Greifswald
Asklepios Kliniken Hamburg Altona
Hamburg
University Medical Center Schleswig-Holstein
Kiel, 24105
Universitatsklinikum Schleswig-Holstein Campus Luebeck
Lübeck
About this study
Official title: REducing Deaths Due to OXidative Stress The REDOXS© Study
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.
Read the detailed 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).
- Conditions
- Critical Illness, Sepsis, Multiple Organ Failure
- Being tested
- Glutamine, Antioxidants, Glutamine + Antioxidants, Placebo
- Keywords
- randomized trial, antioxidants, glutamine, organ failure
- Medical subject headings
- Critical Illness, Sepsis, Multiple Organ Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GlutamineOther
0.35 gm/kg/day parenterally and 30 gms/day enterally
AntioxidantsOther
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 + AntioxidantsOther
Also called Dipeptiven, Microselenium/Selenium injection/selenase, EN REDOX formula (from Fresenius Kabi, Germany)
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
PlaceboOther
Normal saline intravenously and EN placebo formula (from Fresenius Kabi, Germany)
| Study group | Role | What they receive |
|---|---|---|
| Glutamine | Experimental | Glutamine supplementation Receives: Other: Glutamine |
| Antioxidants | Experimental | Antioxidant supplementation Receives: Other: Antioxidants |
| Glutamine + Antioxidants | Experimental | Glutamine and antioxidant supplementation Receives: Other: Glutamine + Antioxidants |
| Placebo | Placebo comparator | Non-isonitrogenic, iso-caloric placebo solution Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
28-day Mortality
28-day mortality/status: at 28 days after randomization;
Measured: Day 28
Secondary outcomes (3)
ICU Length of Stay
Measure of the duration of participant stay in the ICU
Measured: Day 28
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.
Measured: Day 28
Hospital Length of Stay
Measure of the duration of the participant's hospital stay
Measured: 6 months (from ICU admission)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2005 (estimated)
- Study startApr 2005
- Primary completionDec 2011
- Study completionMay 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Critical IllnessStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,223 participants (actual)
Sponsor and investigators
- Lead sponsor
- Daren K. Heyland
- Sponsor type
- University, hospital or other
- Collaborators
- Fresenius Kabi
- Responsible party
- Sponsor-investigator, Daren K. Heyland, Clinical Evaluation Research Unit at Kingston General Hospital
- Investigators
- Daren Heyland, MD, Study chair, Clinical Evaluation Research Unit, Kingston General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00133978
- Sponsor's protocol ID
- REDOXS
- Other IDs
- EudraCT-No: 2007-001831-73
- Acronym
- REDOXS
- Status last verified
- Dec 2020
- First submitted
- 22 Aug 2005
- Last updated
- 7 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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. doi: 10.1177/0148607103027005355.
PubMed 12971736Heyland 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. doi: 10.1007/s00134-004-2522-z. Epub 2004 Dec 17.
PubMed 15605227Novak 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. doi: 10.1097/00003246-200209000-00011.
PubMed 12352035Heyland 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: 10.1056/NEJMoa1212722.
PubMed 23594003Heyland DK, Elke G, Cook D, Berger MM, Wischmeyer PE, Albert M, Muscedere J, Jones G, Day AG; Canadian Critical Care Trials Group. Glutamine and antioxidants in the critically ill patient: a post hoc analysis of a large-scale randomized trial. JPEN J Parenter Enteral Nutr. 2015 May;39(4):401-9. doi: 10.1177/0148607114529994. Epub 2014 May 5.
PubMed 24803474
Study at a glance
From the registry record, last updated by the sponsor on 7 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- REducing Deaths Due to OXidative Stress The REDOXS© Study
- ClinicalTrials.gov ID
- NCT00133978
- Acronym / sponsor ID
- REDOXS / REDOXS
- Conditions
- Critical Illness, Sepsis, Multiple Organ Failure
- Keywords
- randomized trial, antioxidants, glutamine, organ failure
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,223 participants (actual)
- Lead sponsor
- Daren K. HeylandUniversity, hospital or other
- Collaborators
- Fresenius Kabi
- Study start
- Apr 2005
- Primary completion
- Dec 2011 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 24 Aug 2005 (estimated)
- Results
- Posted 9 Sep 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Glutamine | Experimental | Other: GlutamineGlutamine supplementation |
| Antioxidants | Experimental | Other: AntioxidantsAntioxidant supplementation |
| Glutamine + Antioxidants | Experimental | Other: Glutamine + AntioxidantsGlutamine and antioxidant supplementation |
| Placebo | Placebo comparator | Other: PlaceboNon-isonitrogenic, iso-caloric placebo solution |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Mechanically ventilated patients > or = 18 years old
- 2 or more organ failures related to acute illness
Key exclusion criteria (14 listed)
- > 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Glutamine0.35 gm/kg/day parenterally and 30 gms/day enterally | Other | Glutamine |
| Antioxidants500 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 | Other | Antioxidants |
| Glutamine + AntioxidantsAlso: Dipeptiven, Microselenium/Selenium injection/selenase, EN REDOX formula (from Fresenius Kabi, Germany)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 | Other | Glutamine + Antioxidants |
| PlaceboNormal saline intravenously and EN placebo formula (from Fresenius Kabi, Germany) | Other | Placebo |
Primary outcome
28-day Mortality
Time frame: Day 28
28-day mortality/status: at 28 days after randomization;
3 secondary outcomes
ICU Length of Stay
Time frame: Day 28
ICU Acquired Infection
Time frame: Day 28
Hospital Length of Stay
Time frame: 6 months (from ICU admission)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 12971736Heyland 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. doi: 10.1177/0148607103027005355.
- Background: PubMed 15605227Heyland 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. doi: 10.1007/s00134-004-2522-z. Epub 2004 Dec 17.
- Background: PubMed 12352035Novak 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. doi: 10.1097/00003246-200209000-00011.
- Results publication: PubMed 23594003Heyland 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: 10.1056/NEJMoa1212722.
- Derived from this study: PubMed 24803474Heyland DK, Elke G, Cook D, Berger MM, Wischmeyer PE, Albert M, Muscedere J, Jones G, Day AG; Canadian Critical Care Trials Group. Glutamine and antioxidants in the critically ill patient: a post hoc analysis of a large-scale randomized trial. JPEN J Parenter Enteral Nutr. 2015 May;39(4):401-9. doi: 10.1177/0148607114529994. Epub 2014 May 5.
- Click here for more information about this study: A Randomized Trial of Glutamine and Antioxidant Supplementation in Critically Ill PatientsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daren Heyland, MD study chair
Clinical Evaluation Research Unit, Kingston General Hospital
34 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Glutamine, Antioxidants and Glutamine + Antioxidants in people with Critical Illness and Sepsis, run by Daren K. Heyland at 34 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 34 sites in Canada, United States, Germany, Belgium, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Sep 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
28-day Mortality (time frame: Day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00133978, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jan 2021.