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

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.

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.

Study Overview

• Status: Terminated
• Conditions: Traumatic Brain Injury
• Intervention / Treatment: Device: Arctic Sun; Drug: Magnesium Sulfate

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Hollywood, Florida, United States, 33021
      • Memorial Regional Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adult males or females ≥ 18 years of age
2. Subjects with Traumatic Brain Injury and a post-resuscitation Glasgow Coma Score (GCS) ≤ 8
3. In-hospital and screened within 7 hours of injury.
4. Able to obtain legally effective written consent from authorized representative
5. Patients who are intubated and on mechanical ventilation
6. Admitted to ICU

Exclusion Criteria:

1. Bladder or rectal core temperature below 32C (89.6F) upon admission
2. Clinical brain death
3. Patients with open abdomens.
4. Multiple orthopedic injuries (> 2 long bone fractures)
5. Persistent hypotension (systolic blood pressure < 90mmHg)
6. Persistent hypoxia (O2 Saturation < 94%)
7. Persistent metabolic acidosis (Lactic acid > 5 mmol/L, arterial pH < 7.25)
8. Positive serum pregnancy test
9. Cardiac arrhythmia with deleterious hemodynamic effects; heart block or myocardial damage (as shown on ECG)
10. History of abnormal renal function
11. Significant Co-morbidity (i.e. CAD;COPD; severe coagulopathy)
12. Pediatric patients (< 18 years old)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: Conventional Therapy
EXPERIMENTAL: Hypothermia; Subjects will have their core body temperatures lowered to 34C.	Device: Arctic Sun; Core Body Temperature will be lowered using an Arctic Sun device to 34C. Bladder probe will monitor core temperature.
EXPERIMENTAL: Hypothermia plus supplemental magnesium sulfate infusion	Device: Arctic Sun; Core Body Temperature will be lowered using an Arctic Sun device to 34C. Bladder probe will monitor core temperature.; Drug: Magnesium Sulfate; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: United States Department of Defense
• Investigators: Principal Investigator: Greg Zorman, MD, Memorial Healthcare System

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (ACTUAL): March 1, 2014
• Study Completion (ACTUAL): June 1, 2014

Study Registration Dates

• First Submitted: April 8, 2011
• First Submitted That Met QC Criteria: April 11, 2011
• First Posted (ESTIMATE): April 12, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): October 28, 2015
• Last Update Submitted That Met QC Criteria: October 27, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Brain; Traumatic; Injury
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Body Temperature Changes; Brain Injuries; Wounds and Injuries; Brain Injuries, Traumatic; Hypothermia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics; Membrane Transport Modulators; Anticonvulsants; Calcium-Regulating Hormones and Agents; Reproductive Control Agents; Calcium Channel Blockers; Tocolytic Agents; Magnesium Sulfate
• Other Study ID Numbers: MHS TBI Study