Glutamine Supplementation in Critically Ill Patients With Severe Sepsis

Study Overview
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Brief Summary
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Severe sepsis is a common condition with high mortality and morbidity. A previous meta-analysis has demonstrated the safety of glutamine supplementation with suggestion of mortality and morbidity benefits in critically ill patients. But there is lack of evidence to recommend the use of intravenous glutamine supplementation in this population group. A randomized controlled trial which is adequately powered will resolve this issue and can be included in future international nutrition guidelines for the critically ill. This pilot study is done prior to a proposed local multi-center study to investigate the effects of glutamine supplementation.

Detailed Description
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Objective To determine the effect of intravenous glutamine supplementation compared with placebo in critically ill patients with severe sepsis Primary outcome : 28 day mortality , Development of infectious complications Secondary outcomes Duration of mechanical ventilation Length of stay in ICU Length of stay in hospital 3 month survival status and resumption of baseline activities 6 month survival status and resumption of baseline activities Study Design Single center, prospective, double blind, randomised controlled trial critically ill patients with severe sepsis Randomisation A centralised randomisation system at SCRI (Singapore Clinical Research institute) Allocation will be random and concealed, and will be blinded to everyone except the pharmacist at each site, who will be responsible for preparing and delivering them to the ICU in a blinded fashion. Intervention Patients randomised to receive glutamine supplementation will receive IV glutamine (0.5g/kg body weight/day) continuously over 24 hours. IV glutamine will be administered for 5 days or less if death ensues prior to 5 days or transferred to another hospital prior to 5 days. IV glutamine will be continued even if the patient is transferred outside the ICU but within the hospital. An intravenous saline solution that is identical in volume, color and consistency will be administered to the placebo group with the same dosing regimen and duration. Cointerventions Nutritional support will be continued as per managing ICU team discretion. Management of severe sepsis will be continued as per managing ICU team discretion. Weaning patients from mechanical ventilation will be done as per managing ICU team discretion. To minimise differences between centers, active dissemination of practice guidelines for nutritional support, sepsis management and weaning will be carried out. Execution of study protocol The managing ICU team will be responsible in identifying patients that meet the inclusion and exclusion criteria and will inform the site research coordination The site research coordinator will be responsible for the following Obtaining consent from relatives of the patients Informing the site pharmacist about the recruited patients Follow study patients prospectively while in the ICU, hospital and post discharge at 3 and 6 months. Completing the case report from for each study participant Submitting case report forms, completed and interim reports, to coordinating statistical team Pharmacist Site pharmacist to liase with SCRI on randomised patients status (treatment vs. placebo) Prepare the intervention treatment and placebo Deliver the treatment and placebo to the respective patients. Nurses Responsible for administering the delivered medications Ensure and documenting compliance with administration, reasons for interruptions and documenting adverse reactions. Liasing with the site research coordinator daily regarding the above. Liasing with the site research coordinator on transfer, discharge or death of study participants

Official Title
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A Randomized Controlled Trial of Glutamine Supplementation in Critically Ill Adults With Severe Sepsis: A Pilot Study

Conditions
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Severe Sepsis

Intervention / Treatment
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* Dietary Supplement: Glutamine
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria All adult patients (>18 years old) admitted to ICU plus Severe sepsis defined as 2 or more or the following Temperature >38oC or < 36oC Heart rate > 90 beats per min Respiratory rate >20 breaths per min or PaCO2 <32 mmHg White cell count > 12,000/microL or < 4,000/microL PLUS presence or presumed presence of infection PLUS evidence of organ dysfunction as defined by either of the following Hemodynamic: Hypotension = systolic blood pressure (SBP) 40 mm Hg or mean arterial pressure (MAP) < 65 mm Hg; or on vasopressors Hyperlactatemia: Serum lactate >/= 2 mmol/L (18 mg/dL) Renal: Acute increase in serum creatinine to > 176.8 mmol/L (2.0 mg/dL) or urine output < 0.5 mL/kg/hour for > 2 hours Lung: Acute lung injury with PaO2/FiO2 </=300mmHg Liver: Acute increase in bilirubin to >/= 34.2 umol/L (2 mg/dL) Thrombocytopenia: Acute decrease in platelet count to < 100,000 cells/mm3 Coagulopathy: International normalized ratio (INR) > 1.5 or a partial thromboplastin time (aPTT) > 60 secs which is not due to anticoagulant therapy Exclusion criteria >48hr from admission to ICU Patients who are not expected to survive >48hrs by the managing team Refusal to consent to study Allergic to glutamine or its constituents Absolute contraindication to enteral nutrition or the need to initiate parenteral nutrition Patients with a primary admission diagnosis of burns (>30% body surface area) Patients whose weight <40kg or >200kg Previous randomization to this study Enrolled in a related ICU interventional nutrition study Pregnant patients or lactating mothers with the intent to breastfeed

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo | Dietary Supplement: Placebo<br>* Nutritional support will be continued as per managing ICU team discretion. Management of severe sepsis will be continued as per managing ICU team discretion. Weaning patients from mechanical ventilation will be done as per managing ICU team discretion. To minimise differences between centers, active dissemination of practice guidelines for nutritional support, sepsis management and weaning will be carried out.<br>|
| Active Comparator: Glutamine<br>Glutamine | Dietary Supplement: Glutamine<br>* Patients randomised to receive glutamine supplementation will receive IV glutamine (0.5g/kg body weight/day) continuously over 24 hours. IV glutamine will be administered for 5 days or less if death ensues prior to 5 days or transferred to another hospital prior to 5 days. IV glutamine will be continued even if the patient is transferred outside the ICU but within the hospital. An intravenous saline solution that is identical in volume, color and consistency will be administered to the placebo group with the same dosing regimen and duration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality |  | 28 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of new infections |  | Initial hospital admission, assessed up to 130 days. | 
| ICU length of stay (LOS) |  | From date of ICU admission to date of transferred to General Ward or date of death from any cause, whichever came first, assessed up to 21 days. | 
| Hospital LOS |  | From date of recruitment to date of discharged from hospital or date of transferred to other hospitals or date of death from any cause, whichever came first, assessed up to 130 days. | 
| Duration of mechanical ventilation |  | During period of ICU stay, assessed up to 14 days. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glutamine, Severe sepsis