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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: May 9, 2012
Last verified: May 2012
History of Changes
  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:

U.S. FDA Resources

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

Primary Outcome Measures:
  • The primary outcome for this study is 28-day mortality. [ Time Frame: 28 day mortality ] [ Designated as safety issue: No ]
    28-day mortality/status: at 28 days after randomization; 14 day mortality/status: at 14 days after randomization; Hospital mortality, % died in hospital, % discharged from hospital, % alive and still in hospital; Kaplan-Meier survival curves to 6 months; Subgroup analyses: two vs more than two organ failures on presentation, severity of illness, sepsis vs other admission diagnosis, age, comorbidity


Secondary Outcome Measures:
  • Intensive Care Unit (ICU) Outcomes [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    Duration of Mechanical ventilation (ventilator-free days), time from randomization to final mechanical ventilation discontinuation); ICU Length of stay; Survival (time from randomization to death)

  • ICU Acquired Infection [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    Adjudicated infection category and rate of positive culture.

  • Sequential Organ Failure Assessment (SOFA) [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    Daily SOFA score; maximal SOFA score; Delta SOFA

  • Hospital Outcomes [ Time Frame: 6 months (from ICU admission) ] [ Designated as safety issue: No ]
    Duration of mechanical ventilation (ventilator-free days, time from randomization to final mechanical ventilation discontinuation); Hospital length of stay; survival (time from randomization to death)

  • PODS: Composite end point [ Time Frame: Day 60 ] [ Designated as safety issue: No ]
    at day 28; at day 60

  • Health Related Quality of Life [ Time Frame: 6 months (from ICU admission) ] [ Designated as safety issue: No ]
    SF-36 at 3-months; SF-36 at 6-months

  • Shock [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    Duration of shock; shock-free days


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
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:
Click here for more information about this study: A Randomized Trial of Glutamine and Antioxidant Supplementation in Critically Ill Patients  This link exits the ClinicalTrials.gov site

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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
Last Updated: May 9, 2012
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
Sepsis
Disease Attributes
Pathologic Processes
Shock
Infection
 Systemic Inflammatory Response Syndrome
Inflammation
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 19, 2013