Brain Injuries, Traumatic
Conditions
Brief summary
The purpose of this study is test the effect of beta-adrenergic blockade on mortality in patients with traumatic brain injury with the hypothesis being that the addition of beta blockade to the treatment regime of this patient population will lower mortality and supress the catecholamine surge that accompanies traumatic brain injury as compared to those who do not receive beta blockade. Half the patients will be randomized to receive propranolol and half will be randomized to receive no beta blocker.
Detailed description
The use of Beta-adrenergic blockade is not currently the standard of care of patients with traumatic brain injury. Traumatic brain injury is a common problem in our society with greater than 1.5 million cases occurring annually and over 50,000 deaths per year in the civilian population in the United States. Medical therapy has long consisted of monitoring intracranial pressure and supportive measures designed to limit intracranial pressure. Two retrospective observational studies completed at the University of Tennessee demonstrate that the addition of beta-adrenergic blockage to the treatment of the traumatic brain injury lessens mortality. The basis for conducting this study was established by retrospective data showing no harm to patients receiving Inderal and potential benefit. Available data, including data from the University of Tennessee, are retrospective and are limited to simple exposure to the drug. The proposed study will attempt to further quantify the effect by dosing with the drug to actual beta-blockade instead of simple exposure to the drug. The effect of propranolol at the dosing levels used in this research will be determined by measurement of urinary catecholamines in both study arms and comparison of the actual effect of the drug on the catecholamine surge that occurs following traumatic brain injury will be determined. Additionally, the effect of healthcare disparities on outcomes in patients with traumatic brain injury will be measured. Outcomes will be stratified by payer status and ethnicity to determine the effect each of these variables has on outcomes.
Interventions
DRUGPropranolol
Sponsors
University of Tennessee
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
* Subjects ages 18 and older with isolated traumatic brain injury as defined by Glasgow Coma Scale score 12 or less with documented injury on head CT and limited injury to the rest of the body. (Abbreviated Injury Scale (AIS) must be \< or = 3 from other body areas.)
Exclusion criteria
* Subjects \<18 years of age, prisoners, those on beta-blockers as home medication, those who are pregnant, those with severe liver disease, those taking vasopressors, those with acute coronary syndrome, and those with severe injury to another body region (AIS \>3). * Subjects who cannot be enrolled within 48 hours of admission following acute resuscitation will not be enrolled into this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mortality | 30 day | Mortality will be assessed at day 30 or at hospital discharge |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Urine Catecholamine Levels | Collected at baseline, Day 2, Day 5, Day 10 and Day 14. | Urine catecholamine levels will be measured in the hospital laboratory |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Propranolol Arm One half of qualifying and consenting subjects will be randomized to receive propranolol. This group will receive study drug 3 times daily (every 8 hours) starting at 20 mg. The dosage may be increased by up to 60 mg/day divided over three daily doses (or an additional 20 mg/dose) as necessary until the heart rate is less than 100. Study drug will be held for hypotension (systolic \<100) or bradycardia (heart rate \<60 beats per minute). The maximum daily dose for the treatment of hypertension of 640 mg will not be exceeded in this study.
Propranolol | 13 |
| Non Propranolol Arm Non beta blockade arm will receive standard of care treatment and will not receive beta blockade. If a subject randomized to no Inderal develops hypertension and increased heart rate, he/she will be treated according to standard of care by the trauma team caring for the patient. | 12 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | Non Propranolol Arm | Total | Propranolol Arm |
|---|---|---|---|
| Age, Continuous | 53.0 years STANDARD_DEVIATION 21.9 | 51.3 years STANDARD_DEVIATION 20.1 | 49.7 years STANDARD_DEVIATION 19 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Sex: Female, Male Female | 5 Participants | 9 Participants | 4 Participants |
| Sex: Female, Male Male | 7 Participants | 16 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 13 | 4 / 12 |
| other Total, other adverse events | 1 / 13 | 0 / 12 |
| serious Total, serious adverse events | 0 / 13 | 0 / 12 |
Outcome results
Primary
Mortality
Mortality will be assessed at day 30 or at hospital discharge
Time frame: 30 day
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Propranolol Arm | Mortality | 7.7 percentage of participants |
| Non Propranolol Arm | Mortality | 33.3 percentage of participants |
Secondary
Urine Catecholamine Levels
Urine catecholamine levels will be measured in the hospital laboratory
Time frame: Collected at baseline, Day 2, Day 5, Day 10 and Day 14.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Propranolol Arm | Urine Catecholamine Levels | Baseline | 236.4 microgram/L | Standard Error 56.3 |
| Propranolol Arm | Urine Catecholamine Levels | Day 5 | 308.5 microgram/L | Standard Error 51.29 |
| Propranolol Arm | Urine Catecholamine Levels | Day 2 | 263.6 microgram/L | Standard Error 51.56 |
| Propranolol Arm | Urine Catecholamine Levels | Day 14 | 375.3 microgram/L | Standard Error 56.06 |
| Propranolol Arm | Urine Catecholamine Levels | Day 10 | 324.4 microgram/L | Standard Error 51.67 |
| Non Propranolol Arm | Urine Catecholamine Levels | Day 14 | 275.7 microgram/L | Standard Error 44.06 |
| Non Propranolol Arm | Urine Catecholamine Levels | Day 10 | 216.7 microgram/L | Standard Error 50.52 |
| Non Propranolol Arm | Urine Catecholamine Levels | Baseline | 278.0 microgram/L | Standard Error 52.1 |
| Non Propranolol Arm | Urine Catecholamine Levels | Day 2 | 181.9 microgram/L | Standard Error 59.28 |
| Non Propranolol Arm | Urine Catecholamine Levels | Day 5 | 200.1 microgram/L | Standard Error 48.19 |