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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Canadian Institutes of Health Research (CIHR)
American Burn Association
Information provided by (Responsible Party):
Daren K. Heyland, Clinical Evaluation Research Unit at Kingston General Hospital
ClinicalTrials.gov Identifier:
NCT00985205
First received: September 25, 2009
Last updated: March 3, 2015
Last verified: March 2015
  Purpose

The purpose of this study is to test the following hypotheses:

  1. Enteral glutamine administration decreases in-hospital mortality in adult subjects with severe thermal burn injuries.
  2. Enteral glutamine administration decreases infectious morbidity and shortens length of care in adult subjects with severe thermal burn injuries.
  3. Enteral glutamine administration decreases the cost of care of adult subjects with severe thermal burn injuries.

The objectives of this proposed pilot trial relate to evaluating the feasibility of the study protocol. Specifically, the investigators want to assess the following outcomes in a sample of 200 patients in 8 sites:

  1. Number of patients enrolled per site per month and reasons for non-enrollment.
  2. Rate of consent for eligible patients.
  3. Rate of adherence to study interventions and reasons for non-adherence

Condition Intervention Phase
Burns
Dietary Supplement: Enteral Glutamine
Dietary Supplement: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of Enteral Glutamine Supplementation on Mortality and Infectious Morbidity in Severely Burned Patients: a Multi-center Pilot Trial

Resource links provided by NLM:


Further study details as provided by Clinical Evaluation Research Unit at Kingston General Hospital:

Primary Outcome Measures:
  • Hospital mortality [ Time Frame: 7 days after last grafting procedure ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 6 month mortality [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Incidence of infections [ Time Frame: 10 days after last grafting procedure ] [ Designated as safety issue: Yes ]
  • Length of Care [ Time Frame: 7 days after last grafting procedure ] [ Designated as safety issue: Yes ]
  • Length of mechanical ventilation [ Time Frame: Number of days on ventilator up to 6 months ] [ Designated as safety issue: Yes ]
  • Length of ICU stay [ Time Frame: All days with assisted ventilation up to 6 months ] [ Designated as safety issue: Yes ]
  • SOFA Score [ Time Frame: Daily while mechanically ventilated up to 6 months ] [ Designated as safety issue: Yes ]
  • APACHE II Score [ Time Frame: Once - calculated per data from the first 24 hours of ICU admission ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 200
Study Start Date: December 2010
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Enteral Glutamine
0.5 gm/kg/day mixed in water and given via nasogastric tube as boluses q 4 hrs or TID if po
Dietary Supplement: Enteral Glutamine
0.5g/kg/day powdered glutamine to be mixed in with water and given via nasogastric tube q4 hrs or TID if po.
Other Name: Glutamine
Placebo Comparator: Placebo
Mixed in with water and given via nasogastric tube as boluses q 4hrs or TID if po
Dietary Supplement: Placebo
Maltodextrin mixed with water given via NG tube Q 4 hours or TID if po.
Other Name: Maltodextrin

Detailed Description:

Enteral glutamine has been found to decrease mortality in critically ill patients and blood infection in trauma patients. In our pilot study (Critical Care Medicine, 2003, 31:2444) we found the same 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. Since such a large multi center study has never been conducted in burn patients, a pilot study that will test its feasibility seems warranted.

The mechanism of action of glutamine is controversial. Improvement in T cell immune functions, anti-oxidant properties and a newly discovered action on heat shock proteins could all be involved. If our clinical hypothesis is supported by the results of this trial, additional grant proposals will be made to test several mechanistic hypotheses, using blood samples obtained from a randomly determined sub-group of patients stratified for severity of the injury.

The specific aims of the pilot study will be to determine recruitment rates, compliance with nutritional burn management protocol and with study intervention. Clinical outcomes will be: mortality, incidence of infectious episodes, clinical status during the ICU stay and length of care in adult with severe burns.

The study will be a multi-center, prospective, double blinded, and controlled randomised clinical trial. Randomization will be concealed and stratified for burn severity. Patients will be adults, a minimum of 18 years old, admitted within 48h post burn, with deep 2nd and/or 3rd degree burns requiring grafting, and for patients age 18 - 59 years a (Total Burn Surface Area) TBSA ≥ 20% or in the presence of an inhalation injury a minimum of 15% TBSA is required; for patients aged 60 years or older a TBSA ≥ 10% is required. The pilot study will include approximately 8 burn centers, 2 in Canada and 6 in the US and enrol 200 patients over four years. These patients will be included in the final analysis of the complete trial. Compliance with study protocols and with study intervention will be assessed through regular on site visits, regular phone contacts and teleconferences.

Glutamine or a placebo will be given every 6 hours at 0.5 gm/kg/day as boluses or orally, until 7 days post last successful graft, discharge from the burn unit, or 6 months from ICU admission, whatever comes first. Resuscitation, nutritional support, pain management, infection control and surgical care will be done according to standardized procedures.

Participating sites that choose to collect labs for the mechanistic studies will collect approximately 30 mls (2 Tablespoons) of blood on days 4, 7, 14 and 21 to test the effect of glutamine on inflammatory response and the time-course of inflammation, immunosuppression and the production of heat shock proteins Samples will be drawn on CPT tubes for white blood cells isolation.

The end points of the study are: Primary: Recruitment rates, Compliance with study protocols and compliance with study intervention. Secondary: mortality, incidence of infectious episodes, ICU length of care, length of care, and multiple organ functions. 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 infections with glutamine. These outcomes will be measured but not analysed during this pilot trial.

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Deep 2nd and/or 3rd degree burns requiring grafting
  2. a.) Patients 18 - 59 years of age without inhalation injury TBSA* ≥ 20% b.) Patients 18 - 59 years of age with inhalation injury TBSA* ≥ 15% c.) Patients ≥ 60 years of age (with or without inhalation injury) TBSA* ≥ 10%

    • TBSA - Total Burn Surface Area

Exclusion Criteria:

  1. > 72 hrs from admission to ICU to time of consent.
  2. Patients younger than 18 years of age
  3. Liver cirrhosis - Child's class C liver disease
  4. Pregnancy
  5. Absolute contra-indication for EN: intestinal occlusion or perforation, abdominal injury
  6. Patients admitted more than 48h post burn
  7. Patients with injuries from high voltage electrical shock
  8. Patients who are moribund
  9. Patients with extreme body sizes: BMI < 18 or > 50
  10. Enrolment 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, or corn products
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00985205

Locations
United States, Colorado
Department of Anesthesiology, University of Colorado
Aurora, Colorado, United States, 80045
United States, Georgia
Joseph M Still Burn Center
Augusta, Georgia, United States, 30909
United States, Iowa
Department of Surgery University of Iowa Hospitals & Clinics
Iowa City, Iowa, United States, 52242
United States, Missouri
Mercy Hospital St. Louis
St. Louis, Missouri, United States, 63141
United States, Oregon
Legacy Emmanuel Hospital & Health Center
Portland, Oregon, United States, 97232
United States, Tennessee
The University of Tennessee Health Science Center
Memphis, Tennessee, United States, TG032
United States, Wisconsin
Columbia St. Mary's
Milwaukee, Wisconsin, United States, 53211
Canada, Alberta
Firefighters' Burn Treatment Unit Plastic Surgery Wound Healing Research Laboratory
Edmonton, Alberta, Canada, T6G 2B7
Canada, Ontario
Ross Tilley Burn Centre, Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada, M4N 3M5
Sponsors and Collaborators
Daren K. Heyland
Canadian Institutes of Health Research (CIHR)
American Burn Association
Investigators
Study Chair: Dominique Garrel, MD Université de Montréal
Study Chair: Paul Wischmeyer, MD University of Colorado, Denver
  More Information

Additional Information:
Publications:
Responsible Party: Daren K. Heyland, Professor of Medicine, Clinical Evaluation Research Unit at Kingston General Hospital
ClinicalTrials.gov Identifier: NCT00985205     History of Changes
Other Study ID Numbers: RE-ENERGIZE, CIHR # 190808
Study First Received: September 25, 2009
Last Updated: March 3, 2015
Health Authority: Canada: Health Canada

Keywords provided by Clinical Evaluation Research Unit at Kingston General Hospital:
Randomized Clinical Trial
Glutamine
Themal Burn Injuries
Nutrition
Outcome Assessment
Critical Care
Total Burn Surface Area

ClinicalTrials.gov processed this record on March 03, 2015