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

August 22, 2005
May 9, 2012
April 2005
December 2011   (final data collection date for primary outcome measure)
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
The primary outcome for this study is 28-day mortality.
Complete list of historical versions of study NCT00133978 on ClinicalTrials.gov Archive Site
  • 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
The secondary outcomes are duration of stay in ICU, adjudicated diagnosis of infection, multiple organ dysfunction, duration of mechanical ventilation, hospital length of stay, and health-related quality of life at 3 and 6 months.
Not Provided
Not Provided
 
Trial of Glutamine and Antioxidant Supplementation in Critically Ill Patients
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.

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).

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Critical Illness
  • Sepsis
  • Multiple Organ Failure
  • Other: Glutamine
    0.35 gm/kg/day parenterally and 30 gms/day enterally
  • 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
  • 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)
  • Other: Placebo
    Normal saline intravenously and EN placebo formula (from Fresenius Kabi, Germany)
  • Experimental: Glutamine
    Glutamine supplementation
    Intervention: Other: Glutamine
  • Experimental: Antioxidants
    Antioxidant supplementation
    Intervention: Other: Antioxidants
  • Experimental: Glutamine + Antioxidants
    Glutamine and antioxidant supplementation
    Intervention: Other: Glutamine + Antioxidants
  • Placebo Comparator: Placebo
    Non-isonitrogenic, iso-caloric placebo solution
    Intervention: Other: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1223
May 2012
December 2011   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Belgium,   Canada,   Germany,   Switzerland
 
NCT00133978
REDOXS, EudraCT-No: 2007-001831-73
Yes
Daren K. Heyland, Clinical Evaluation Research Unit at Kingston General Hospital
Daren K. Heyland
Fresenius Kabi
Study Chair: Daren Heyland, MD Clinical Evaluation Research Unit, Kingston General Hospital
Clinical Evaluation Research Unit at Kingston General Hospital
May 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP