Mild Hypothermia and Supplemental Magnesium Sulfate Infusion in Severe Traumatic Brain Injury (TBI) Subjects

Study Overview
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Brief Summary
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The investigators hypothesize that hypothermia (body cooling) and additional magnesium sulfate will improve the outcome of severe Traumatic Brain Injury (TBI) patients. This is a study to compare the outcomes of patients with severe traumatic brain injury who have been allocated to one of the following three groups: Group 1 - Conventional therapy following traumatic brain injury Group 2 - Subjects will have their core body temperature lowered to 34C Group 3 - Subjects will have their core body temperature lowered to 34C and will receive a supplemental intravenous infusion of magnesium sulfate.

Official Title
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A Phase 2, Randomized, Controlled 2x3 Trial Comparing Clinical Outcomes in Patients With Severe Traumatic Brain Injury Using Mild Hypothermia and Concurrent and Supplemental Infusion of Magnesium Sulfate.

Conditions
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Traumatic Brain Injury

Intervention / Treatment
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* Device: Arctic Sun
* Drug: Magnesium Sulfate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult males or females ≥ 18 years of age Subjects with Traumatic Brain Injury and a post-resuscitation Glasgow Coma Score (GCS) ≤ 8 In-hospital and screened within 7 hours of injury. Able to obtain legally effective written consent from authorized representative Patients who are intubated and on mechanical ventilation Admitted to ICU Exclusion Criteria: Bladder or rectal core temperature below 32C (89.6F) upon admission Clinical brain death Patients with open abdomens. Multiple orthopedic injuries (> 2 long bone fractures) Persistent hypotension (systolic blood pressure < 90mmHg) Persistent hypoxia (O2 Saturation < 94%) Persistent metabolic acidosis (Lactic acid > 5 mmol/L, arterial pH < 7.25) Positive serum pregnancy test Cardiac arrhythmia with deleterious hemodynamic effects; heart block or myocardial damage (as shown on ECG) History of abnormal renal function Significant Co-morbidity (i.e. CAD;COPD; severe coagulopathy) Pediatric patients (< 18 years old)

Ages Eligible for Study
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Minimum Age: 18 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Conventional Therapy<br> | |
| Experimental: Hypothermia<br>Subjects will have their core body temperatures lowered to 34C. | Device: Arctic Sun<br>* Core Body Temperature will be lowered using an Arctic Sun device to 34C. Bladder probe will monitor core temperature.<br>|
| Experimental: Hypothermia plus supplemental magnesium sulfate infusion<br> | Device: Arctic Sun<br>* Core Body Temperature will be lowered using an Arctic Sun device to 34C. Bladder probe will monitor core temperature.<br>Drug: Magnesium Sulfate<br>* IVI drug levels of Magnesium Sulfate targeted to plasma levels of magnesium of 2.5-3.5 mEq/Liter.(1.25-1.75mmol/L; or 3.04 - 4.26mg/dL)for 72 hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GOS (Glasgow Outcome Score) | GOS=5 (Good Recovery) - Capacity to resume normal occupational and social activities, although some there may be some minor physical or mental deficits or symptoms. GOS=4 (Moderate Disability) - Independent and can resume almost all activities of daily living. GOS=3 (Severe Disability) - No longer capable of engaging in most previous personal, social or work activities. Typically are partially or totally dependent on assistance from others in daily living. GOS=2 ( Persistent Vegetative State ) GOS=1 (Dead) | Discharge from Hospital - Within 2 months from Injury | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GOS | GOS score | 12 months after injury | 
| Vasospasm | as measured by TCD (Transcranial Doppler) | up to 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Traumatic, Brain, Injury