Overview

This trial is active, not recruiting.

Conditions brain injuries, craniocerebral trauma, trauma, nervous system, traumatic brain injury
Treatments iv propranolol and per tube clonidine, placebo
Phase phase 2
Sponsor Vanderbilt University
Collaborator Vanderbilt Institute for Clinical and Translational Research (CTSA)
Start date August 2011
End date January 2015
Trial size 100 participants
Trial identifier NCT01322048, 110429

Summary

The investigators intend to determine the effect of adrenergic blockade on 1) short-term physiology, behavior, and cognition and 2) long-term neuropsychological outcomes after severe Traumatic Brain Injury (TBI).

The primary hypothesis is that adrenergic blockade after severe TBI will be associated with increased ventilator-free days.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Propranolol and Clonidine
iv propranolol and per tube clonidine
1 mg IV q6h Propranolol and 0.1 mg Per Tube Clonidine, both for 7 days
(Placebo Comparator)
Placebo
placebo
Placebo IV q6h and Per Tube q12, both for 7 days

Primary Outcomes

Measure
Ventilator-free days
time frame: Baseline to hospital discharge (average t = Day 30)

Secondary Outcomes

Measure
Plasma Catecholamine Levels
time frame: Baseline, Post-treatment (t=Day 8)
24h Urinary Catecholamine Levels
time frame: Baseline, Post-treatment (t=Day 8)
Daily percentage of low heart rate variability (HRV) intervals
time frame: Baseline to ICU Discharge (average t = Day 14)
Change in Low frequency to high frequency ratio from heart rate variability analysis
time frame: Post-treatment (t= Day 8 )
RASS score
time frame: Twice daily to hospital discharge (average t = Day 30)
Agitation Behavior Scale (ABS) score
time frame: Twice daily to hospital discharge (average t = Day 30)
Glasgow Coma Scale (GCS) score
time frame: Twice daily to hospital discharge (average t = Day 30)
Daily pulse pressure variability
time frame: Baseline to ICU discharge (average t = Day 14)
Coma-free days
time frame: Baseline to hospital discharge (average t = Day 30)
ICU Length of Stay
time frame: Baseline to ICU discharge (average t = Day 14)
Hospital length of stay
time frame: Baseline to hospital discharge (average t = Day 30)
Quality of Life after Brain Injury (QOLIBRI)
time frame: 3 months, 12 months
Extended Glasgow Outcome Scale (GOSE)
time frame: At 3 months, 12 months
Neuropsychological Assessment
time frame: At hospital discharge (average t = Day 30), 3 months, 12 months
Adjunct medication use
time frame: Baseline to hospital discharge (average t = Day 30)
Cardiac Complications
time frame: Baseline to ICU discharge (average t = Day 14)
Patient Health Questionnaire (PHQ-9)
time frame: 3 months, 12 months
Rancho Los Amigos Level of Cognitive Functioning
time frame: At hospital discharge (average t = Day 30)
Cerebral Blood Velocity
time frame: Baseline, Post-treatment (t=Day 8)

Eligibility Criteria

Male or female participants from 16 years up to 64 years old.

Inclusion Criteria: - Age: 16 years to 64 years - Glasgow Coma Scale score less than or equal to 8 (Severe TBI) with injury on CT - Screen within 24 hours of injury Exclusion Criteria: - Pre-existing heart disease (i.e. coronary heart disease) - Pre-existing cardiac dysrhythmia - Allergy to study drugs - Penetrating brain injury - Pre-existing brain dysfunction (i.e. prior severe TBI, debilitating stroke) - Impending brain herniation (i.e. loss of bilateral corneal reflexes) - Craniectomy or craniotomy - Spinal cord injury - Myocardial injury - Severe liver disease - Current use of beta-blockers and/or alpha-2-agonist - Withdrawal of care expected in 24 hours - Prisoners - Pregnant women - Unable to follow-up through final visit

Additional Information

Official title DASH After TBI Study: Decreasing Adrenergic or Sympathetic Hyperactivity After Severe Traumatic Brain Injury, A Pilot Randomized Clinical Trial Using Propranolol and Clonidine
Principal investigator Mayur B Patel, MD, MPH
Description Severe traumatic brain injury (TBI) is associated with sympathetic hyperactivity resulting in catecholamine excess, abnormal heart rate variability, agitation and sympathetic storms, deep white matter changes, and poor neuropsychological outcomes. Notably, persistent sympathetic hyperactivity after TBI results in higher days of mechanical ventilation and longer intensive care unit (ICU) length of stay (LOS). While there are data describing limited portions of this response, the full spectrum of sympathetic hyperactivity after severe TBI has not been systemically described or methodically intervened upon. We will perform a double-blinded, randomized, placebo-controlled pilot trial in a 100 patient cohort in which one group will receive centrally acting sympatholytic drugs, propranolol and clonidine, and the other group, placebo, within 48 hours of severe TBI. The length of therapy will be 7 days. The primary question studied is whether ventilator-free days will be increased after therapy. Secondary endpoints include plasma and urine catecholamine levels, heart rate and blood pressure variability, responses to autonomic cold pressor testing, assessments of coma, sedation, and agitation, sedative requirements, analgesic use, antipsychotic medication use, coma-free days, ventilator-free days, Intensive Care Unit (ICU) length of stay, and survival. Also, neuropsychological outcomes will be measured at ICU discharge, 3 months, and 12 months. Interim Analysis: At approximately 50% targeted accrual, n=46 randomized subjects, an interim analysis will be performed with A Priori (planned) futility and efficacy rules, which are DSMB and IRB approved.
Trial information was received from ClinicalTrials.gov and was last updated in September 2015.
Information provided to ClinicalTrials.gov by Vanderbilt University.