Beta Blockade in in Traumatic Brain Injury

Study Overview
=================
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.

Official Title
-----------------
Beta-Adrenergic Blockade for Suppression of Catecholamine Surge Following Traumatic Brain Injury: A Randomized Trial

Conditions
-----------------
Brain Injuries, Traumatic

Intervention / Treatment
-----------------
* Drug: Propranolol


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Propranolol arm<br>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. | Drug: Propranolol<br> <br> * Other names: Inderal;|
| No Intervention: Non propranolol arm<br>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. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | Mortality will be assessed at day 30 or at hospital discharge | 30 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urine Catecholamine Levels | Urine catecholamine levels will be measured in the hospital laboratory | Collected at baseline, Day 2, Day 5, Day 10 and Day 14. |