Traumatic Brain Injury
Conditions
Keywords
Traumatic, Brain, Injury
Brief summary
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.
Interventions
DEVICEArctic Sun
Core Body Temperature will be lowered using an Arctic Sun device to 34C. Bladder probe will monitor core temperature.
DRUGMagnesium 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.
Sponsors
United States Department of Defense
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| GOS (Glasgow Outcome Score) | Discharge from Hospital - Within 2 months from Injury | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| GOS | 12 months after injury | GOS score |
| Vasospasm | up to 3 months | as measured by TCD (Transcranial Doppler) |
Countries
United States
Participant flow
Recruitment details
Recruitment dates from 11/3/2011 to 3/10/2014 in Level one trauma center setting. Study was closed because of low accrual.
Participants by arm
| Arm | Count |
|---|---|
| Conventional Therapy Standard of care therapy for severe traumatic brain injury. | 2 |
| Hypothermia Subjects will have their core body temperatures lowered to 34C.
Arctic Sun: Core Body Temperature will be lowered using an Arctic Sun device to 34C. Bladder probe will monitor core temperature. | 1 |
| Hypothermia Plus Supplemental Magnesium Sulfate Infusion Arctic Sun: Core Body Temperature will be lowered using an Arctic Sun device to 34C. Bladder probe will monitor core temperature.
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. | 3 |
| Total | 6 |
Baseline characteristics
| Characteristic | Hypothermia | Hypothermia Plus Supplemental Magnesium Sulfate Infusion | Conventional Therapy | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 3 Participants | 2 Participants | 6 Participants |
| Age, Continuous | 43 years | 25.6 years | 35.5 years | 32 years |
| Region of Enrollment United States | 1 participants | 3 participants | 2 participants | 6 participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 1 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 1 / 2 | 0 / 1 | 2 / 3 |
Outcome results
Primary
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)
Time frame: Discharge from Hospital - Within 2 months from Injury
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Conventional Therapy | GOS (Glasgow Outcome Score) | 3 units on a scale |
| Hypothermia | GOS (Glasgow Outcome Score) | 3 units on a scale |
| Hypothermia Plus Supplemental Magnesium Sulfate Infusion | GOS (Glasgow Outcome Score) | 3 units on a scale |
Secondary
GOS
GOS score
Time frame: 12 months after injury
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Conventional Therapy | GOS | 5 GOS score |
| Hypothermia | GOS | 5 GOS score |
| Hypothermia Plus Supplemental Magnesium Sulfate Infusion | GOS | 4 GOS score |
Secondary
Vasospasm
as measured by TCD (Transcranial Doppler)
Time frame: up to 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Conventional Therapy | Vasospasm | 100 Percentage of participants |
| Hypothermia | Vasospasm | 0 Percentage of participants |
| Hypothermia Plus Supplemental Magnesium Sulfate Infusion | Vasospasm | 66.6 Percentage of participants |