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

December 11, 2020 updated by: Daren K. Heyland

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

1223

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Brussels, Belgium
        • UZ Brussels
      • Liege, Belgium, B-4000
        • University Hospital
  • Canada
      • Quebec, Canada, G1J 1Z4
        • Enfant-Jesus
    • Alberta
      • Edmonton, Alberta, Canada, T5H 3V9
        • Royal Alexandra Hospital
      • Edmonton, Alberta, Canada, T6L 5X8
        • Grey Nun's Hospital, Edmonton
    • British Columbia
      • Vancouver, British Columbia, Canada, V6Z 1Y6
        • St Paul's Hospital
      • Vancouver, British Columbia, Canada, V5Z 1C6
        • Vancouver Hospital
      • Victoria, British Columbia, Canada, V8R 1J8
        • Royal Jubilee Hospital
      • Victoria, British Columbia, Canada, V8Z 6R5
        • Victoria General Hospital
    • Manitoba
      • Winnipeg, Manitoba, Canada, R2H 2A6
        • St. Boniface General Hospital
      • Winnipeg, Manitoba, Canada, R3A 1R9
        • Health Science Centre
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H 2Y9
        • Capital Health Queen Elizabeth II HSC
    • Ontario
      • Hamilton, Ontario, Canada, L8N 4A6
        • St Joseph's Healthcare
      • Kingston, Ontario, Canada, K7L 2V7
        • Kingston General Hospital
      • London, Ontario, Canada, N6A 5W9
        • London HSC Victoria Campus, ON
      • Ottawa, Ontario, Canada, K1H 8H6
        • Ottawa Hospital
      • Ottawa, Ontario, Canada, K1Y 4E9
        • Ottawa Hospital Civic Hospital
      • Toronto, Ontario, Canada, M4N 3M5
        • Sunnybrook & Women's College, Toronto
      • Toronto, Ontario, Canada, M5G 1X5
        • Mt Sinai Hospital
    • Quebec
      • Montreal, Quebec, Canada, H3A 1A1
        • Royal Victoria Hospital
      • Montreal, Quebec, Canada, H1T 2M4
        • Hopital Maisonneuve-Rosemount
      • Montreal, Quebec, Canada, H3G 1A4
        • Montreal General
      • Montreal, Quebec, Canada, H4J 1C5
        • Hopital de Sacre-Coeur
  • Germany
      • Greifswald, Germany
        • Universitatsklinikum der Ernst-Moritz-Arndt-Universitat
      • Hamburg, Germany
        • Asklepios Kliniken Hamburg Altona
      • Kiel, Germany, 24105
        • University Medical Center Schleswig-Holstein
      • Lubeck, Germany
        • Universitätsklinikum Schleswig-Holstein Campus Luebeck
  • Switzerland
      • Lausanne, Switzerland, Ch-1011
        • CHUV
      • Zurich, Switzerland
        • University of Zurich
  • United States
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Univ. of Colorado at Denver and Health Sciences Center
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • University of Louisville
    • Ohio
      • Dayton, Ohio, United States, 45409
        • Miami Valley Hospital
    • Texas
      • Houston, Texas, United States, 6431
        • University of Texas
    • Vermont
      • Burlington, Vermont, United States, 05401
        • Fletcher Allan Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Glutamine
Glutamine supplementation
Other: Glutamine
0.35 gm/kg/day parenterally and 30 gms/day enterally
Experimental: Antioxidants
Antioxidant supplementation
Other: Antioxidants
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
Experimental: Glutamine + Antioxidants
Glutamine and antioxidant supplementation
Other: Glutamine + Antioxidants
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 Names:
  • Dipeptiven, Microselenium/Selenium injection/selenase, EN REDOX formula (from Fresenius Kabi, Germany)
Placebo Comparator: Placebo
Non-isonitrogenic, iso-caloric placebo solution
Other: Placebo
Normal saline intravenously and EN placebo formula (from Fresenius Kabi, Germany)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
28-day Mortality
Time Frame: Day 28
28-day mortality/status: at 28 days after randomization;
Day 28

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ICU Length of Stay
Time Frame: Day 28
Measure of the duration of participant stay in the ICU
Day 28
ICU Acquired Infection
Time Frame: Day 28
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.
Day 28
Hospital Length of Stay
Time Frame: 6 months (from ICU admission)
Measure of the duration of the participant's hospital stay
6 months (from ICU admission)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Daren K. Heyland

Collaborators

Fresenius Kabi

Investigators

  • Study Chair: Daren Heyland, MD, Clinical Evaluation Research Unit, Kingston General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2005

Primary Completion (Actual)

December 1, 2011

Study Completion (Actual)

May 1, 2012

Study Registration Dates

First Submitted

August 22, 2005

First Submitted That Met QC Criteria

August 22, 2005

First Posted (Estimate)

August 24, 2005

Study Record Updates

Last Update Posted (Actual)

January 7, 2021

Last Update Submitted That Met QC Criteria

December 11, 2020

Last Verified

December 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • REDOXS
  • EudraCT-No: 2007-001831-73

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe