The RE-ENERGIZE Study: RandomizEd Trial of ENtERal Glutamine to minimIZE Thermal Injury
- Conditions
- Burns
- Interventions
- Dietary Supplement: Enteral GlutamineDietary Supplement: Placebo
- Registration Number
- NCT00985205
- Lead Sponsor
- Daren K. Heyland
- Brief Summary
The purpose of this study is to test the following hypotheses:
1. Enteral glutamine administration decreases in-hospital mortality in adult patients with severe thermal burn injuries.
2. Enteral glutamine administration decreases hospital-acquired blood stream infections from Gram negative organisms and length of stay in ICU and hospital for adult patients with severe thermal burn injuries.
3. Enteral glutamine administration will improve the physical function of surviving burn injured patients and reduce their cost of care.
The objectives of this trial are to determine the overall treatment effect and safety of glutamine in burn patients. Specifically, the investigators want to assess the following outcomes in a sample of 1200 patients in 80 sites:
1. In patients with severe, life-threatening burn injury, what is the effect of enteral glutamine on time to discharge alive from hospital
2. In patients with severe, life-threatening burn injury, what is the effect of enteral glutamine on 6 month mortality, hospital-acquired blood stream infections from Gram negative organisms, hospital mortality, duration of stay in ICU and hospital, health-related quality of life, and health care resources?
- Detailed Description
Burn injuries represent a public health problem worldwide, ranked fourth in all injuries and are among the leading cause of disability adjusted life years in low and middle-income countries. More than in any other injury, the inflammation and catabolism associated with severe burns can exacerbate nutrient deficiencies, thereby predisposing patients to impaired immune function and increased risk of developing infectious complications, organ dysfunction, and death. Consequently, over the last few decades numerous trials have evaluated the impact of different nutrition/nutrient strategies in severe burns patients. Glutamine is of particular interest in this regard as it appears vital for a number of key stress-response pathways in serious illness. The existing randomized trials of glutamine supplementation in burns patients have suggested a significant reduction in mortality, infection, and hospital length of stay. However, in other critically ill patient populations, there is a signal of increased mortality associated with glutamine administration. Given this conflicting evidence, burn practitioners are either harming or saving lives with glutamine use. We hypothesize that the inexpensive therapeutic strategy tested in this multicenter randomized controlled clinical trial of supplemental enteral glutamine in 1200 severe burn injury patients will lead to lower morbidity and mortality and reduced health care costs in an otherwise very devastating and disabling injury worldwide.
In our pilot study (Critical Care Medicine, 2003, 31:2444) we found a protective effect of glutamine against blood infection in severely burned adult patients. In addition, a significant decrease in mortality was observed with glutamine. These results should be tested with a multi-center trial because our study was small and did not have mortality as an end point.
The specific aims of the study are to determine the overall treatment effect and safety of glutamine in burn patients. Clinical outcomes will be: mortality, time to discharge alive, incidence of acquired bacteremia due to Gram negative organisms, hospital mortality, duration of mechanical ventilation, ICU stay and hospital stay. The cost-effectiveness of glutamine administration will also be measured if the results show a decrease in length of care or a reduced incidence of acquired bacteremia due to Gram negative organisms with glutamine.
The study will be a large, multicenter, double-blind, pragmatic, randomized controlled trial of 1200 patients with severe burns randomly allocated to receive enteral glutamine or placebo. Randomization will be concealed and stratified by site allocating patients 1:1 to either glutamine or matching placebo by the method of permuted blocks of random undisclosed size within strata. Patients will be adults, a minimum of 18 years old, with deep 2nd and/or 3rd degree burns requiring grafting, and for patients age 18 - 39 years a (Total Body Surface Area) TBSA burn ≥ 20% or in the presence of an inhalation injury a minimum of 15% TBSA burn is required; for patients age 40 - 59 years a TBSA burn ≥ 15% is required; for patients aged 60 years or older a TBSA burn ≥ 10% is required. The study will include approximately 80 burn centers in Canada, the US, Europe and Latin America. Patients will receive glutamine or a placebo through their feeding tube, every 4 hours or TID or QID if taking things by mouth, for a total of 0.5 g/kg/day for patients with a BMI \<35. Patients with a BMI ≥35 will receive 0.5 g/kg/day based on an obesity-adjusted body weight. The study intervention will be administered until ≥7 days after the last successful grafting operation or until discharge from acute care unit or 3 months from admission, whichever comes first. Resuscitation, nutritional support, pain management, infection control and surgical care will be done according to standardized procedures.
The Data will be collected and managed by a professional and centralized organization for multi centres clinical research (Clinical Evaluation Research Unit, Kingston, Ontario, Canada).
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 1201
-
Deep 2nd and/or 3rd degree burns requiring grafting
-
Patient meets one of the following 4 criteria:
- Patients 18 - 39 years of age with ≥ 20% TBSA* burn
- Patients 18 - 39 years of age with ≥ 15% TBSA* burn and with inhalation injury
- Patients 40 - 59 years of age with ≥ 15% TBSA* burn
- Patients ≥ 60 years of age ≥ 10% TBSA* *TBSA - Total Body Surface Area
-
> 72 hrs from admission to ICU to time of consent.
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Patients younger than 18 years of age.
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a) Patients without known renal disease and renal dysfunction defined as a serum creatinine >171 µmol/L or a urine output of less than 500 mL/last 24 hours (or 80 mL/last 4 hours if a 24 hour period of observation is not available).
b) Patients with acute on chronic renal failure (pre-dialysis) with an absolute increase of >80 µmol/L from baseline or pre-admission creatinine or a urine output of <500 mL/last 24 hours (or 80 mL/last 4 hours).
c) Patients with chronic renal failure on dialysis will be excluded.
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Liver cirrhosis - Child-Pugh class C liver disease
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Pregnant or lactating females.
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Contra-indication for EN: intestinal occlusion or perforation, intra-abdominal injury.
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Patients with injuries from high voltage electrical contact.
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Patients who are moribund (not expected to survive the next 72 hours).
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Patients with extreme body sizes: BMI < 18 or > 50
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Enrollment in another industry sponsored ICU intervention study.
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Received glutamine supplement for > 24 hrs prior to randomization
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Known allergy to maltodextrin, corn starch, corn, corn products or glutamine.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Enteral Glutamine Enteral Glutamine 0.5 g/kg/day mixed in water and given via nasogastric or feeding tube as boluses q 4 hrs or TID or QID if po Placebo Placebo Mixed in with water and given via nasogastric or feeding tube as boluses q 4hrs or TID or QID if po
- Primary Outcome Measures
Name Time Method Time to Discharge Alive 3 months
- Secondary Outcome Measures
Name Time Method 6 Month Mortality 6 Months
Trial Locations
- Locations (53)
The Western Pennsylvania Hospital Burn Center
🇺🇸Pittsburgh, Pennsylvania, United States
Ross Tilley Burn Centre, Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
Centro Nacional de Quemaduras y Cirugia Reconstructiva
🇵🇾Asunción, Paraguay
Memorial Hermann/UTHSC
🇺🇸Houston, Texas, United States
CHUM/Centre des Grands Brules
🇨🇦Montreal, Quebec, Canada
RWTH Aachen University
🇩🇪Aachen, North Rhine-Westphalia, Germany
University Hospitals Birmingham NHS Foundation Trust
🇬🇧Birmingham, Edgbaston, United Kingdom
Columbia-St. Mary's, Milwaukee, Wi
🇺🇸Milwaukee, Wisconsin, United States
Department of Anesthesiology, University of Colorado
🇺🇸Aurora, Colorado, United States
University of South Florida/Tampa Gen. Hosp. Reg. Burn Center, FL
🇺🇸Tampa, Florida, United States
University of South Alabama Medical Center
🇺🇸Mobile, Alabama, United States
Southern California Regional Burn Ctr at LAC & USC Med. Ctr.
🇺🇸Los Angeles, California, United States
Arizona Burn Center at Maricopa Medical Center
🇺🇸Phoenix, Arizona, United States
Shriners Hospitals for Children Northern California
🇺🇸Sacramento, California, United States
Connecticut Burn Center
🇺🇸Bridgeport, Connecticut, United States
North Colorado Medical Center - Banner Health
🇺🇸Greeley, Colorado, United States
Joseph M Still Burn Center
🇺🇸Augusta, Georgia, United States
Shands Burn Center at the University of Florida
🇺🇸Gainesville, Florida, United States
Department of Surgery University of Iowa Hospitals & Clinics
🇺🇸Iowa City, Iowa, United States
The Burn Center at Washington Hospital Center
🇺🇸Washington, District of Columbia, United States
Mercy Hospital St. Louis
🇺🇸Saint Louis, Missouri, United States
CHI St.Elizabeth Regional Burn Center
🇺🇸Lincoln, Nebraska, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
The Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Akron's Children's Hospital, Paul & Carol David Foundation
🇺🇸Akron, Ohio, United States
The Ohio State University Wexnar Medical Center
🇺🇸Columbus, Ohio, United States
Legacy Emmanuel Hospital & Health Center
🇺🇸Portland, Oregon, United States
Firefighters' Regional Burn Center TN, University of Tennesse Health & Sciences Center
🇺🇸Memphis, Tennessee, United States
University of Texas Southwestern
🇺🇸Dallas, Texas, United States
JBSA Fort Sam Houston
🇺🇸Fort Sam Houston, Texas, United States
University of Texas Medical Branch
🇺🇸Galveston, Texas, United States
Harbourview Medical Center
🇺🇸Seattle, Washington, United States
Ghent University Hospital
🇧🇪Ghent, Belgium
Medical University of Graz
🇦🇹Graz, Styria, Austria
The Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
🇧🇷São Paulo, Brazil
University Hospital of Liège
🇧🇪Liège, Belgium
HHS/Hamilton Firefighters Burn Unit
🇨🇦Hamilton, Ontario, Canada
Foothills Medical Centre
🇨🇦Calgary, Alberta, Canada
Siriraj Hospital, Divison of Trauma Surgery, Mahidol University
🇹🇭Bangkok, NOI, Thailand
Berufsgenossenschaftliche Unfallklinik Ludwigshafen
🇩🇪Ludwigshafen, Rhein, Germany
A.O.U. Citta della Salute e della Scienza di Torino
🇮🇹Torino, TO, Italy
HEJ/Centre des Grands Brules
🇨🇦Quebec, Canada
Instituto Tecnologico de Santo Domingo
🇩🇴Santo Domingo, Dominican Republic
Hospital Universitario La Fe
🇪🇸Valencia, Spain
St Helens & Knowsley Teaching Hospitals
🇬🇧Liverpool, England, United Kingdom
King Chulalongkorn Memorial Hospital Chulalongkorn University
🇹🇭Bangkok, Pathumwan, Thailand
Khon Kaen University
🇹🇭Mueang Nonthaburi, Thailand
Uppsala University Hospital
🇸🇪Uppsala, Sweden
Newcastle upon Tyne Hospitals
🇬🇧Newcastle Upon Tyne, England, United Kingdom
Chelsea and Westminster Hospital
🇬🇧London, England, United Kingdom
Manchester University NHSFT
🇬🇧Manchester, London, United Kingdom
Pinderfields Hospital, Mid Yorkshire NHS Trust
🇬🇧London, West Yorkshire, United Kingdom
Singapore General Hospital
🇸🇬Singapore, Singapore