A Phase 2 interventional study of IV Propranolol and Per Tube Clonidine and Placebo in Brain Injuries, Craniocerebral Trauma and Trauma, Nervous System, sponsored by Vanderbilt University. Completed at 1 site in United States. Open to participants aged 16 Years to 64 Years. Per ClinicalTrials.gov, last updated 2017-08-17.
Sponsored by Vanderbilt University · Phase 2, Interventional, and Treatment
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.
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.
2,114 studies on the registry are indexed under Brain Injuries; 386 are open to participants now.
This study's enrollment of 48 is close to the median of 48 across 1,332 interventional studies indexed under Brain Injuries.
Browse Brain Injuries studies →Vanderbilt University is the lead sponsor of 508 studies on the registry; 19 are open to participants now.
Of its 7 completed or terminated interventional studies of FDA-regulated products, 5 (71%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Propranolol and Clonidine
Drug: IV Propranolol and Per Tube Clonidine
Placebo
Drug: Placebo
1 mg IV q6h Propranolol and 0.1 mg Per Tube Clonidine, both for 7 days
Placebo IV q6h and Per Tube q12, both for 7 days
Ventilator-free Days
Time frame: Baseline to day 28
Plasma Norepinephrine Levels
Time frame: Post-treatment (t=Day 8)
| Milestone | Adrenergic Blockade | Placebo |
|---|---|---|
| Started | 21 | 26 |
| Completed | 21 | 26 |
| Not completed | 0 | 0 |
| days | Adrenergic Blockade | Placebo |
|---|---|---|
| Ventilator-free Days | 16.2 (5.5 to 20.1) | 18.05 (0.075 to 20.45) |
| pg/mL | Adrenergic Blockade | Placebo |
|---|---|---|
| Plasma Norepinephrine Levels | 962 (508 to 1471) | 714 (391 to 1257) |
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Adrenergic Blockade | 5/21 (23.8%) | 0/21 (0%) | 0/21 (0%) |
| Placebo | 8/26 (30.8%) | 0/26 (0%) | 0/26 (0%) |
| Age, Continuous(years) | Adrenergic Blockade | Placebo | Total |
|---|---|---|---|
| Median | 24 (21 to 34) | 27.5 (18.5 to 36) | 25 (19 to 34) |
| Sex: Female, Male(Participants) | Adrenergic Blockade | Placebo | Total |
|---|---|---|---|
| Female | 5 | 1 | 6 |
| Male | 16 | 25 | 41 |
| Ethnicity (NIH/OMB)(Participants) | Adrenergic Blockade | Placebo | Total |
|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 |
| Not Hispanic or Latino | 21 | 26 | 47 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Adrenergic Blockade | Placebo | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 2 | 2 | 4 |
| White | 19 | 24 | 43 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(Participants) | Adrenergic Blockade | Placebo | Total |
|---|---|---|---|
| United States | 21 | 26 | 47 |
This study is completed, as verified in Jul 2017. You cannot join it, but the record below documents what was studied.
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