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

This study has been completed.
Sponsor:
Collaborator:
Fresenius Kabi
Information provided by (Responsible Party):
Daren K. Heyland, Clinical Evaluation Research Unit at Kingston General Hospital
ClinicalTrials.gov Identifier:
NCT00133978
First received: August 22, 2005
Last updated: August 26, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Critical Illness
Sepsis
Multiple Organ Failure
Other: Glutamine
Other: Antioxidants
Other: Glutamine + Antioxidants
Other: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: REducing Deaths Due to OXidative Stress The REDOXS© Study

Resource links provided by NLM:


Further study details as provided by Clinical Evaluation Research Unit at Kingston General Hospital:

Primary Outcome Measures:
  • 28-day Mortality [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    28-day mortality/status: at 28 days after randomization;


Secondary Outcome Measures:
  • ICU Length of Stay [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    Measure of the duration of participant stay in the ICU

  • ICU Acquired Infection [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months (from ICU admission) ] [ Designated as safety issue: No ]
    Measure of the duration of the participant's hospital stay


Enrollment: 1223
Study Start Date: April 2005
Study Completion Date: May 2012
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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)

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00133978

  Show 34 Study Locations
Sponsors and Collaborators
Daren K. Heyland
Fresenius Kabi
Investigators
Study Chair: Daren Heyland, MD Clinical Evaluation Research Unit, Kingston General Hospital
  More Information

Additional Information:
Publications:
Responsible Party: Daren K. Heyland, Director, Clinical Evaluation Research Unit at Kingston General Hospital
ClinicalTrials.gov Identifier: NCT00133978     History of Changes
Other Study ID Numbers: REDOXS, EudraCT-No: 2007-001831-73
Study First Received: August 22, 2005
Results First Received: April 29, 2013
Last Updated: August 26, 2014
Health Authority: Canada: Health Canada
Canada: Canadian Institutes of Health Research
Switzerland: Swissmedic
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Clinical Evaluation Research Unit at Kingston General Hospital:
randomized trial
antioxidants
glutamine
organ failure

Additional relevant MeSH terms:
Critical Illness
Multiple Organ Failure
Disease Attributes
Pathologic Processes
Shock
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents

ClinicalTrials.gov processed this record on November 25, 2014