The RE-ENERGIZE Study: RandomizEd Trial of ENtERal Glutamine to minimIZE Thermal Injury
The purpose of this study is to test the following hypotheses:
- Enteral glutamine administration decreases in-hospital mortality in adult subjects with severe thermal burn injuries.
- Enteral glutamine administration decreases infectious morbidity and shortens length of care in adult subjects with severe thermal burn injuries.
- 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:
- Number of patients enrolled per site per month and reasons for non-enrollment.
- Rate of consent for eligible patients.
- Rate of adherence to study interventions and reasons for non-adherence
Dietary Supplement: Enteral Glutamine
Dietary Supplement: Placebo
|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|
- Hospital mortality [ Time Frame: 7 days after last grafting procedure ] [ Designated as safety issue: Yes ]
- 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 ]
|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)|
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
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).
Please refer to this study by its ClinicalTrials.gov identifier: NCT00985205
|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|
|Firefighters' Burn Treatment Unit Plastic Surgery Wound Healing Research Laboratory|
|Edmonton, Alberta, Canada, T6G 2B7|
|Ross Tilley Burn Centre, Sunnybrook Health Sciences Centre|
|Toronto, Ontario, Canada, M4N 3M5|
|Study Chair:||Dominique Garrel, MD||Université de Montréal|
|Study Chair:||Paul Wischmeyer, MD||University of Colorado, Denver|