The RE-ENERGIZE Study: RandomizEd Trial of ENtERal Glutamine to minimIZE Thermal Injury

Burns Clinical Trial

— RE-ENERGIZE  

Official title:

Effects of Enteral Glutamine Supplementation on Mortality and Infectious Morbidity in Severely Burned Patients: a Multi-center Pilot Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00985205
• Other study ID #: RE-ENERGIZE
• Secondary ID: CIHR # 190808
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 2010
• Est. completion date: December 2021

Study information

• Verified date: December 2021
• Source: Clinical Evaluation Research Unit at Kingston General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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?

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 1201
• Est. completion date: December 2021
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Deep 2nd and/or 3rd degree burns requiring grafting

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:

1. > 72 hrs from admission to ICU to time of consent.

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.

Related Conditions & MeSH terms

• Burns

Intervention

Dietary Supplement:
• 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.

Locations

Country	Name	City	State
Austria	Medical University of Graz	Graz	Styria
Belgium	Ghent University Hospital	Ghent
Belgium	University Hospital of Liège	Liège
Brazil	The Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo	São Paulo
Canada	Foothills Medical Centre	Calgary	Alberta
Canada	HHS/Hamilton Firefighters Burn Unit	Hamilton	Ontario
Canada	CHUM/Centre des Grands Brules	Montreal	Quebec
Canada	HEJ/Centre des Grands Brules	Quebec
Canada	Ross Tilley Burn Centre, Sunnybrook Health Sciences Centre	Toronto	Ontario
Dominican Republic	Instituto Tecnologico de Santo Domingo	Santo Domingo
Germany	RWTH Aachen University	Aachen	North Rhine-Westphalia
Germany	Berufsgenossenschaftliche Unfallklinik Ludwigshafen	Ludwigshafen	Rhein
Italy	A.O.U. Citta della Salute e della Scienza di Torino	Torino	TO
Paraguay	Centro Nacional de Quemaduras y Cirugia Reconstructiva	Asunción
Singapore	Singapore General Hospital	Singapore
Spain	Hospital Universitario La Fe	Valencia
Sweden	Uppsala University Hospital	Uppsala
Thailand	King Chulalongkorn Memorial Hospital Chulalongkorn University	Bangkok	Pathumwan
Thailand	Siriraj Hospital, Divison of Trauma Surgery, Mahidol University	Bangkok	NOI
Thailand	Khon Kaen University	Mueang Nonthaburi
United Kingdom	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	Pinderfields Hospital, Mid Yorkshire NHS Trust	London	West Yorkshire
United Kingdom	Manchester University NHSFT	Manchester	London
United Kingdom	Newcastle upon Tyne Hospitals	Newcastle Upon Tyne	England
United States	Akron's Children's Hospital, Paul & Carol David Foundation	Akron	Ohio
United States	Joseph M Still Burn Center	Augusta	Georgia
United States	Department of Anesthesiology, University of Colorado	Aurora	Colorado
United States	Connecticut Burn Center	Bridgeport	Connecticut
United States	The Ohio State University Wexnar Medical Center	Columbus	Ohio
United States	University of Texas Southwestern	Dallas	Texas
United States	JBSA Fort Sam Houston	Fort Sam Houston	Texas
United States	Shands Burn Center at the University of Florida	Gainesville	Florida
United States	University of Texas Medical Branch	Galveston	Texas
United States	North Colorado Medical Center - Banner Health	Greeley	Colorado
United States	Memorial Hermann/UTHSC	Houston	Texas
United States	Department of Surgery University of Iowa Hospitals & Clinics	Iowa City	Iowa
United States	CHI St.Elizabeth Regional Burn Center	Lincoln	Nebraska
United States	Southern California Regional Burn Ctr at LAC & USC Med. Ctr.	Los Angeles	California
United States	Firefighters' Regional Burn Center TN, University of Tennesse Health & Sciences Center	Memphis	Tennessee
United States	Columbia-St. Mary's, Milwaukee, Wi	Milwaukee	Wisconsin
United States	University of South Alabama Medical Center	Mobile	Alabama
United States	The Nebraska Medical Center	Omaha	Nebraska
United States	Arizona Burn Center at Maricopa Medical Center	Phoenix	Arizona
United States	The Western Pennsylvania Hospital Burn Center	Pittsburgh	Pennsylvania
United States	Legacy Emmanuel Hospital & Health Center	Portland	Oregon
United States	Shriners Hospitals for Children Northern California	Sacramento	California
United States	Mercy Hospital St. Louis	Saint Louis	Missouri
United States	Harbourview Medical Center	Seattle	Washington
United States	University of South Florida/Tampa Gen. Hosp. Reg. Burn Center, FL	Tampa	Florida
United States	The Burn Center at Washington Hospital Center	Washington	District of Columbia
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Daren K. Heyland	Canadian Institutes of Health Research (CIHR)

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Brazil,  Canada,  Dominican Republic,  Germany,  Italy,  Paraguay,  Singapore,  Spain,  Sweden,  Thailand,  United Kingdom, 

References & Publications (3)

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Health-Related Quality of Life - in particular the physical function domain of the SF-36, ADL, and IADL questionnaires.		6 Month
Other	Incidence of acquired bacteremia due to Gram negative organisms		3 Months
Other	Hospital Mortality		3 Months
Other	Duration of Mechanical Ventilation		3 months
Other	ICU Stay		3 Months
Other	Hospital Stay		3 Months
Primary	Time to Discharge Alive		3 months
Secondary	6 Month Mortality		6 Months

External Links

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