Decreasing adrenergic or sympathetic hyperactivity after severe traumatic brain injury using propranolol and clonidine (DASH After TBI Study): study protocol for a randomized controlled trial

• DOI: 10.1186/1745-6215-13-177
• Publication Date: 2012-09-27T14:32:11Z
• Authors: Mayur B Patel; John W McKenna; JoAnn M Alvarez; Ayaka Sugiura; Judith M Jenkins; Oscar D Guillamon...; Pratik P Pandhari...
• Keywords: Psychomotor agitation; Clinical endpoint

Severe TBI, defined as a Glasgow Coma Scale ≤ 8, increases intracranial pressure and activates the sympathetic nervous system. Sympathetic hyperactivity after TBI manifests catecholamine excess, hypertension, abnormal heart rate variability, agitation, is associated with poor neuropsychological outcome. Propranolol clonidine are centrally acting drugs that may decrease outflow, brain edema, agitation. However, there no prospective randomized evidence available demonstrating feasibility, outcome benefits, safety for adrenergic blockade TBI. The DASH study an actively accruing, single-center, randomized, double-blinded, placebo-controlled, two-arm trial, where one group receives sympatholytic drugs, propranolol (1 mg intravenously every 6 h 7 days) (0.1 per tube 12 days), other group, double placebo, within 48 of severe uses weighted adaptive minimization randomization categories age Marshall head CT classification. Feasibility will be assessed by ability to provide neuroradiology read randomization, treatment contamination, compliance. primary endpoint reduction in plasma norepinephrine level measured on day 8. Secondary endpoints include comprehensive urine levels, arrhythmia occurrence, infections, agitation measures using Richmond Agitation-Sedation Agitated Behavior scale, medication use (anti-hypertensive, sedative, analgesic, antipsychotic), coma-free days, ventilator-free length stay, mortality. Neuropsychological outcomes at hospital discharge 3 months. domains tested global executive function, memory, processing speed, visual-spatial, behavior. Other assessments Extended Outcome Quality Life Brain Injury scale. Safety parameters evaluated cardiac complications. After Study first placebo-controlled trial powered determine feasibility investigate patients If results positive trends, this could pilot larger multicenter clinical trial. effect therapy, would still robust description ClinicalTrials.gov NCT01322048