Trial of Glutamine and Antioxidant Supplementation in Critically Ill Patients

Study Overview
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Brief Summary
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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
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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).

Official Title
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REducing Deaths Due to OXidative Stress The REDOXS© Study

Conditions
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Critical Illness, Sepsis, Multiple Organ Failure

Intervention / Treatment
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* Other: Glutamine
* Other: Antioxidants
* Other: Glutamine + Antioxidants
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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randomized trial, antioxidants, glutamine, organ failure