Traumatic Brain Injury
Conditions
Keywords
Traumatic Brain Injury, Hypothermia
Brief summary
Induction of hypothermia to \< 35˚C by \< 2.5 hours after severe traumatic brain injury, reaching 33˚C by 4 hours after injury and maintained for 48 hours in patients aged 16-45 will result in an increased number of patients with good outcomes at six months after injury compared to patients randomized to normothermia.
Detailed description
NABIS:HIIR was a randomized clinical trial conducted in patients with severe brain injury, age 16-45. Patients were randomized to standard treatment at normothermia or to standard treatment with moderate hypothermia (32.5-34C for 48 hours). An intent to treat analysis was used with the primary outcome measure as the Glasgow Outcome Scale at six months after injury. GOS is dichotomized into good outcome (Good Recovery/Moderate Disability) and poor outcome (Severe Disability, Vegetative, Dead).
Interventions
DEVICEHypothermia
Induction of moderate hypothermia to 33 degrees celsius, within 2.5 hours from time of injury and maintained for 48 hours
Sponsors
National Institute of Neurological Disorders and Stroke (NINDS)
The University of Texas Health Science Center, Houston
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
1. Non-penetrating brain injury with post-resuscitation Glasgow Coma Score (GCS) \< 8 (motor 1-5) 2. Estimated or known age \> 16 and \< 45 years old 3. Time of Injury within 2.5hrs of arrival at hospital
Exclusion criteria
1. GCS = 7 or 8 with a normal head Cat Scan (CT) scan or showing only mild Subarachnoid hemorrhage (SAH)or skull fracture or GCS \> 9 post- randomization 2. GCS = 3 AND bilaterally non-reactive pupils 3. Abbreviated Injury Score (AIS) \> 4 for any body area except head 4. Positive abdominal ultrasound or CT scan 5. Persistent hypotension (systolic blood pressure \< 110mmHGg) 6. Persistent hypoxia (O2 Saturation \< 94%) 7. Positive pregnancy test 8. Injured greater than 2.5 hours from hospital arrival 9. Pre-existing medical conditions, if known
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Dichotomized Glasgow Outcome Scale | 6 months with a window of plus or minus one month | The primary outcome measure was the Glasgow Outcome Scale measured in person six months after injury by examiners who were blinded to the patient's treatment group. Good recovery and moderate disability were designated as favorable outcomes; severe disability, a vegetative state, and death as poor outcomes. |
Other
| Measure | Time frame |
|---|---|
| Disability Rating Scale | assessed 0-12 months |
| Neurobehavioral Rating Scale - Revised | 0-12 months |
| Neurological Outcome Scale for Traumatic Brain Injury | 0-12 months |
| Symbol Digit Modalities Test | 0-12 months |
| Glasgow Outcome Scale - Extended | 0-12 months |
| Verbal Selective Reminding Test Trails B | 0-12 months |
| Grooved Pegboard | 0-12 months |
| Controlled Oral Word Association Test | 0-12 months |
| Rey Osterrieth Complex Figure | 0-12 months |
Countries
Canada, United States
Participant flow
Recruitment details
Patients were enrolled in hospitals of University of Texas Health Science Center at Houston, University of Calgary, University of Pittsburgh, St. Louis University, Charleston Area Medical Center, and University of New Mexico.Enrollment occurred from December 2005 to June 2009 with follow-up from June 2006 through December 2009
Pre-assignment details
Enrollment criteria at the first eligibility assessment were ages 16-45, non-penetrating brain injury, and not responsive to instructions. 232 participants met these criteria and also had none of a first set of exclusion criteria. At the second eligibility assessment, 97 patients had none of a second set of exclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| Hypothermia Induction and maintenance of moderate hypothermia to 33 degrees celsius achieved within 4 hours of injury and maintained for 48 hours.
Hypothermia: Induction of moderate hypothermia to 33 degrees celsius, within 4 hours from time of injury and maintained for 48 hours | 52 |
| Control Treated at normothermia | 45 |
| Total | 97 |
Baseline characteristics
| Characteristic | Hypothermia | Control | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 7 Participants | 6 Participants | 13 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 45 Participants | 38 Participants | 83 Participants |
| Age, Continuous | 26 years STANDARD_DEVIATION 9 | 31 years STANDARD_DEVIATION 11 | 28 years STANDARD_DEVIATION 10 |
| Sex: Female, Male Female | 12 Participants | 4 Participants | 16 Participants |
| Sex: Female, Male Male | 40 Participants | 41 Participants | 81 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 42 / 52 | 38 / 45 | 22 / 67 | 30 / 68 |
| serious Total, serious adverse events | 30 / 52 | 20 / 45 | 11 / 67 | 5 / 68 |
Outcome results
Primary
The Dichotomized Glasgow Outcome Scale
The primary outcome measure was the Glasgow Outcome Scale measured in person six months after injury by examiners who were blinded to the patient's treatment group. Good recovery and moderate disability were designated as favorable outcomes; severe disability, a vegetative state, and death as poor outcomes.
Time frame: 6 months with a window of plus or minus one month
Population: Intention to Treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hypothermia | The Dichotomized Glasgow Outcome Scale | 31 participants with a poor outcome |
| Control | The Dichotomized Glasgow Outcome Scale | 25 participants with a poor outcome |
Comparison: The primary hypothesis was a two-sided test assessing whether the induction of hypothermia modified the percentage of subjects with poor outcomes at 6 months after injury. Percentages in each group were compared using a generalized linear model with a binomial distribution and log link function, logistic regression model with admission age and baseline GCS as covariates.p-value: =0.6795% CI: [0.76, 1.53]Regression, Logistic
Other Pre-specified
Controlled Oral Word Association Test
Time frame: 0-12 months
Other Pre-specified
Disability Rating Scale
Time frame: assessed 0-12 months
Other Pre-specified
Glasgow Outcome Scale - Extended
Time frame: 0-12 months
Other Pre-specified
Grooved Pegboard
Time frame: 0-12 months
Other Pre-specified
Neurobehavioral Rating Scale - Revised
Time frame: 0-12 months
Other Pre-specified
Neurological Outcome Scale for Traumatic Brain Injury
Time frame: 0-12 months
Other Pre-specified
Rey Osterrieth Complex Figure
Time frame: 0-12 months
Other Pre-specified
Symbol Digit Modalities Test
Time frame: 0-12 months
Other Pre-specified
Verbal Selective Reminding Test Trails B
Time frame: 0-12 months