The RE-ENERGIZE Study: RandomizEd Trial of ENtERal Glutamine to minimIZE Thermal Injury
NCT ID: NCT00985205
Last Updated: 2021-12-30
Study Results
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Basic Information
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UNKNOWN
PHASE3
1201 participants
INTERVENTIONAL
2010-12-31
2021-12-31
Brief Summary
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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
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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).
Conditions
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Keywords
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Study Design
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RANDOMIZED
SINGLE_GROUP
TREATMENT
QUADRUPLE
Study Groups
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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
Enteral Glutamine
0.5g/kg/day powdered glutamine to be mixed in with water and given via nasogastric or feeding tube q4 hrs or TID or QID if po.
Placebo
Mixed in with water and given via nasogastric or feeding tube as boluses q 4hrs or TID or QID if po
Placebo
Maltodextrin mixed with water given via NG or feeding tube Q 4 hours or TID or QID if po.
Interventions
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Enteral Glutamine
0.5g/kg/day powdered glutamine to be mixed in with water and given via nasogastric or feeding tube q4 hrs or TID or QID if po.
Placebo
Maltodextrin mixed with water given via NG or feeding tube Q 4 hours or TID or QID if po.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Patient meets one of the following 4 criteria:
1. Patients 18 - 39 years of age with ≥ 20% TBSA\* burn
2. Patients 18 - 39 years of age with ≥ 15% TBSA\* burn and with inhalation injury
3. Patients 40 - 59 years of age with ≥ 15% TBSA\* burn
4. Patients ≥ 60 years of age ≥ 10% TBSA\* \*TBSA - Total Body Surface Area
Exclusion Criteria
2. Patients younger than 18 years of age.
3. 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.
4. Liver cirrhosis - Child-Pugh class C liver disease
5. Pregnant or lactating females.
6. Contra-indication for EN: intestinal occlusion or perforation, intra-abdominal injury.
7. Patients with injuries from high voltage electrical contact.
8. Patients who are moribund (not expected to survive the next 72 hours).
9. Patients with extreme body sizes: BMI \< 18 or \> 50
10. Enrollment in another industry sponsored ICU intervention study.
11. Received glutamine supplement for \> 24 hrs prior to randomization
12. Known allergy to maltodextrin, corn starch, corn, corn products or glutamine.
18 Years
ALL
No
Sponsors
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Canadian Institutes of Health Research (CIHR)
OTHER_GOV
Daren K. Heyland
OTHER
Responsible Party
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Daren K. Heyland
Professor of Medicine
Principal Investigators
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Daren Heyland, MD
Role: PRINCIPAL_INVESTIGATOR
Queen's University
Locations
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University of South Alabama Medical Center
Mobile, Alabama, United States
Arizona Burn Center at Maricopa Medical Center
Phoenix, Arizona, United States
Southern California Regional Burn Ctr at LAC & USC Med. Ctr.
Los Angeles, California, United States
Shriners Hospitals for Children Northern California
Sacramento, California, United States
Department of Anesthesiology, University of Colorado
Aurora, Colorado, United States
North Colorado Medical Center - Banner Health
Greeley, Colorado, United States
Connecticut Burn Center
Bridgeport, Connecticut, United States
The Burn Center at Washington Hospital Center
Washington D.C., District of Columbia, United States
Shands Burn Center at the University of Florida
Gainesville, Florida, United States
University of South Florida/Tampa Gen. Hosp. Reg. Burn Center, FL
Tampa, Florida, United States
Joseph M Still Burn Center
Augusta, Georgia, United States
Department of Surgery University of Iowa Hospitals & Clinics
Iowa City, Iowa, United States
Mercy Hospital St. Louis
St Louis, Missouri, United States
CHI St.Elizabeth Regional Burn Center
Lincoln, Nebraska, United States
The Nebraska Medical Center
Omaha, Nebraska, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 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
The Western Pennsylvania Hospital Burn Center
Pittsburgh, Pennsylvania, 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
Memorial Hermann/UTHSC
Houston, Texas, United States
Harbourview Medical Center
Seattle, Washington, United States
Columbia-St. Mary's, Milwaukee, Wi
Milwaukee, Wisconsin, United States
Medical University of Graz
Graz, Styria, Austria
Ghent University Hospital
Ghent, , Belgium
University Hospital of Liège
Liège, , Belgium
The Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
São Paulo, , Brazil
Foothills Medical Centre
Calgary, Alberta, Canada
HHS/Hamilton Firefighters Burn Unit
Hamilton, Ontario, Canada
Ross Tilley Burn Centre, Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada
CHUM/Centre des Grands Brules
Montreal, Quebec, Canada
HEJ/Centre des Grands Brules
Québec, , Canada
Instituto Tecnologico de Santo Domingo
Santo Domingo, , Dominican Republic
RWTH Aachen University
Aachen, North Rhine-Westphalia, Germany
Berufsgenossenschaftliche Unfallklinik Ludwigshafen
Ludwigshafen, Rhein, Germany
A.O.U. Citta della Salute e della Scienza di Torino
Torino, TO, Italy
Centro Nacional de Quemaduras y Cirugia Reconstructiva
Asunción, , Paraguay
Singapore General Hospital
Singapore, , Singapore
Hospital Universitario La Fe
Valencia, , Spain
Uppsala University Hospital
Uppsala, , Sweden
Siriraj Hospital, Divison of Trauma Surgery, Mahidol University
Bangkok, NOI, Thailand
King Chulalongkorn Memorial Hospital Chulalongkorn University
Bangkok, Pathumwan, Thailand
Khon Kaen University
Nonthaburi, , Thailand
University Hospitals Birmingham NHS Foundation Trust
Birmingham, Edgbaston, United Kingdom
St Helens & Knowsley Teaching Hospitals
Liverpool, England, United Kingdom
Chelsea and Westminster Hospital
London, England, United Kingdom
Newcastle upon Tyne Hospitals
Newcastle upon Tyne, England, United Kingdom
Manchester University NHSFT
Manchester, London, United Kingdom
Pinderfields Hospital, Mid Yorkshire NHS Trust
London, West Yorkshire, United Kingdom
Countries
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References
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Garrel D, Patenaude J, Nedelec B, Samson L, Dorais J, Champoux J, D'Elia M, Bernier J. Decreased mortality and infectious morbidity in adult burn patients given enteral glutamine supplements: a prospective, controlled, randomized clinical trial. Crit Care Med. 2003 Oct;31(10):2444-9. doi: 10.1097/01.CCM.0000084848.63691.1E.
Zhou YP, Jiang ZM, Sun YH, Wang XR, Ma EL, Wilmore D. The effect of supplemental enteral glutamine on plasma levels, gut function, and outcome in severe burns: a randomized, double-blind, controlled clinical trial. JPEN J Parenter Enteral Nutr. 2003 Jul-Aug;27(4):241-5. doi: 10.1177/0148607103027004241.
Peng X, Yan H, You Z, Wang P, Wang S. Effects of enteral supplementation with glutamine granules on intestinal mucosal barrier function in severe burned patients. Burns. 2004 Mar;30(2):135-9. doi: 10.1016/j.burns.2003.09.032.
Heyland DK, Wibbenmeyer L, Pollack J, Friedman B, Turgeon AF, Eshraghi N, Jeschke MG, Belisle S, Grau D, Mandell S, Velamuri SR, Hundeshagen G, Moiemen N, Shokrollahi K, Foster K, Huss F, Collins D, Savetamal A, Gurney JM, Depetris N, Stoppe C, Ortiz-Reyes L, Garrel D, Day AG; RE-ENERGIZE Trial Team. A Randomized Trial of Enteral Glutamine for Treatment of Burn Injuries. N Engl J Med. 2022 Sep 15;387(11):1001-1010. doi: 10.1056/NEJMoa2203364. Epub 2022 Sep 9.
Heyland DK, Wischmeyer P, Jeschke MG, Wibbenmeyer L, Turgeon AF, Stelfox HT, Day AG, Garrel D. A RandomizEd trial of ENtERal Glutamine to minimIZE thermal injury (The RE-ENERGIZE Trial): a clinical trial protocol. Scars Burn Heal. 2017 Dec 12;3:2059513117745241. doi: 10.1177/2059513117745241. eCollection 2017 Jan-Dec.
Provided Documents
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Document Type: Statistical Analysis Plan
Related Links
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Related Info
Other Identifiers
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CIHR # 190808
Identifier Type: OTHER_GRANT
Identifier Source: secondary_id
RE-ENERGIZE
Identifier Type: -
Identifier Source: org_study_id