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Trial of Glutamine and Antioxidant Supplementation in Critically Ill Patients (REDOXS)

Primary Purpose

Critical Illness, Sepsis, Multiple Organ Failure

Status
Completed
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Glutamine
Antioxidants
Glutamine + Antioxidants
Placebo
Sponsored by
Daren K. Heyland
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Critical Illness focused on measuring randomized trial, antioxidants, glutamine, organ failure

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Mechanically ventilated patients > or = 18 years old 2 or more organ failures related to acute illness Exclusion Criteria: > 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 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

Sites / Locations

  • Univ. of Colorado at Denver and Health Sciences Center
  • University of Louisville
  • Miami Valley Hospital
  • University of Texas
  • Fletcher Allan Centre
  • UZ Brussels
  • University Hospital
  • Royal Alexandra Hospital
  • Grey Nun's Hospital, Edmonton
  • Vancouver Hospital
  • St Paul's Hospital
  • Royal Jubilee Hospital
  • Victoria General Hospital
  • St. Boniface General Hospital
  • Health Science Centre
  • Capital Health Queen Elizabeth II HSC
  • St Joseph's Healthcare
  • Kingston General Hospital
  • London HSC Victoria Campus, ON
  • Ottawa Hospital
  • Ottawa Hospital Civic Hospital
  • Sunnybrook & Women's College, Toronto
  • Mt Sinai Hospital
  • Hopital Maisonneuve-Rosemount
  • Royal Victoria Hospital
  • Montreal General
  • Hopital de Sacre-Coeur
  • Enfant-Jesus
  • Universitatsklinikum der Ernst-Moritz-Arndt-Universitat
  • Asklepios Kliniken Hamburg Altona
  • University Medical Center Schleswig-Holstein
  • Universitatsklinikum Schleswig-Holstein Campus Luebeck
  • CHUV
  • University of Zurich

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

Glutamine

Antioxidants

Glutamine + Antioxidants

Placebo

Arm Description

Glutamine supplementation

Antioxidant supplementation

Glutamine and antioxidant supplementation

Non-isonitrogenic, iso-caloric placebo solution

Outcomes

Primary Outcome Measures

28-day Mortality
28-day mortality/status: at 28 days after randomization;

Secondary Outcome Measures

ICU Length of Stay
Measure of the duration of participant stay in the ICU
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.
Hospital Length of Stay
Measure of the duration of the participant's hospital stay

Full Information

First Posted
August 22, 2005
Last Updated
December 11, 2020
Sponsor
Daren K. Heyland
Collaborators
Fresenius Kabi
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1. Study Identification

Unique Protocol Identification Number
NCT00133978
Brief Title
Trial of Glutamine and Antioxidant Supplementation in Critically Ill Patients
Acronym
REDOXS
Official Title
REducing Deaths Due to OXidative Stress The REDOXS© Study
Study Type
Interventional

2. Study Status

Record Verification Date
December 2020
Overall Recruitment Status
Completed
Study Start Date
April 2005 (undefined)
Primary Completion Date
December 2011 (Actual)
Study Completion Date
May 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Daren K. Heyland
Collaborators
Fresenius Kabi

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Critical Illness, Sepsis, Multiple Organ Failure
Keywords
randomized trial, antioxidants, glutamine, organ failure

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Factorial Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
1223 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Glutamine
Arm Type
Experimental
Arm Description
Glutamine supplementation
Arm Title
Antioxidants
Arm Type
Experimental
Arm Description
Antioxidant supplementation
Arm Title
Glutamine + Antioxidants
Arm Type
Experimental
Arm Description
Glutamine and antioxidant supplementation
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Non-isonitrogenic, iso-caloric placebo solution
Intervention Type
Other
Intervention Name(s)
Glutamine
Intervention Description
0.35 gm/kg/day parenterally and 30 gms/day enterally
Intervention Type
Other
Intervention Name(s)
Antioxidants
Intervention Description
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
Intervention Type
Other
Intervention Name(s)
Glutamine + Antioxidants
Other Intervention Name(s)
Dipeptiven, Microselenium/Selenium injection/selenase, EN REDOX formula (from Fresenius Kabi, Germany)
Intervention Description
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
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Normal saline intravenously and EN placebo formula (from Fresenius Kabi, Germany)
Primary Outcome Measure Information:
Title
28-day Mortality
Description
28-day mortality/status: at 28 days after randomization;
Time Frame
Day 28
Secondary Outcome Measure Information:
Title
ICU Length of Stay
Description
Measure of the duration of participant stay in the ICU
Time Frame
Day 28
Title
ICU Acquired Infection
Description
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.
Time Frame
Day 28
Title
Hospital Length of Stay
Description
Measure of the duration of the participant's hospital stay
Time Frame
6 months (from ICU admission)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Mechanically ventilated patients > or = 18 years old 2 or more organ failures related to acute illness Exclusion Criteria: > 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daren Heyland, MD
Organizational Affiliation
Clinical Evaluation Research Unit, Kingston General Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Univ. of Colorado at Denver and Health Sciences Center
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
University of Louisville
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Miami Valley Hospital
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45409
Country
United States
Facility Name
University of Texas
City
Houston
State/Province
Texas
ZIP/Postal Code
6431
Country
United States
Facility Name
Fletcher Allan Centre
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05401
Country
United States
Facility Name
UZ Brussels
City
Brussels
Country
Belgium
Facility Name
University Hospital
City
Liege
ZIP/Postal Code
B-4000
Country
Belgium
Facility Name
Royal Alexandra Hospital
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T5H 3V9
Country
Canada
Facility Name
Grey Nun's Hospital, Edmonton
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6L 5X8
Country
Canada
Facility Name
Vancouver Hospital
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 1C6
Country
Canada
Facility Name
St Paul's Hospital
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6Z 1Y6
Country
Canada
Facility Name
Royal Jubilee Hospital
City
Victoria
State/Province
British Columbia
ZIP/Postal Code
V8R 1J8
Country
Canada
Facility Name
Victoria General Hospital
City
Victoria
State/Province
British Columbia
ZIP/Postal Code
V8Z 6R5
Country
Canada
Facility Name
St. Boniface General Hospital
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R2H 2A6
Country
Canada
Facility Name
Health Science Centre
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R3A 1R9
Country
Canada
Facility Name
Capital Health Queen Elizabeth II HSC
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3H 2Y9
Country
Canada
Facility Name
St Joseph's Healthcare
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 4A6
Country
Canada
Facility Name
Kingston General Hospital
City
Kingston
State/Province
Ontario
ZIP/Postal Code
K7L 2V7
Country
Canada
Facility Name
London HSC Victoria Campus, ON
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5W9
Country
Canada
Facility Name
Ottawa Hospital
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8H6
Country
Canada
Facility Name
Ottawa Hospital Civic Hospital
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1Y 4E9
Country
Canada
Facility Name
Sunnybrook & Women's College, Toronto
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Facility Name
Mt Sinai Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X5
Country
Canada
Facility Name
Hopital Maisonneuve-Rosemount
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 2M4
Country
Canada
Facility Name
Royal Victoria Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3A 1A1
Country
Canada
Facility Name
Montreal General
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3G 1A4
Country
Canada
Facility Name
Hopital de Sacre-Coeur
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4J 1C5
Country
Canada
Facility Name
Enfant-Jesus
City
Quebec
ZIP/Postal Code
G1J 1Z4
Country
Canada
Facility Name
Universitatsklinikum der Ernst-Moritz-Arndt-Universitat
City
Greifswald
Country
Germany
Facility Name
Asklepios Kliniken Hamburg Altona
City
Hamburg
Country
Germany
Facility Name
University Medical Center Schleswig-Holstein
City
Kiel
ZIP/Postal Code
24105
Country
Germany
Facility Name
Universitatsklinikum Schleswig-Holstein Campus Luebeck
City
Lubeck
Country
Germany
Facility Name
CHUV
City
Lausanne
ZIP/Postal Code
Ch-1011
Country
Switzerland
Facility Name
University of Zurich
City
Zurich
Country
Switzerland

12. IPD Sharing Statement

Citations:
PubMed Identifier
12971736
Citation
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.
Results Reference
background
PubMed Identifier
15605227
Citation
Heyland 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.
Results Reference
background
PubMed Identifier
12352035
Citation
Novak 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 Reference
background
PubMed Identifier
23594003
Citation
Heyland 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. Erratum In: N Engl J Med. 2013 May 9;368(19):1853. Dosage error in article text.
Results Reference
result
PubMed Identifier
24803474
Citation
Heyland 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.
Results Reference
derived
Links:
URL
http://www.criticalcarenutrition.com/index.php?option=com_content&task=view&id=19&Itemid=42
Description
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Trial of Glutamine and Antioxidant Supplementation in Critically Ill Patients

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