Trial design
TBI
We conducted a phase II, single-center, randomized, double-blinded, placebo-controlled pilot trial to test whether sympathetic blockade with propranolol and clonidine within 48 h of severe TBI improves clinical outcomes. Our protocol was approved by our Institutional Review Board and registered (NCT01322048). Enrollment took place between August 2011 through January 2015. One group received centrally acting sympatholytic drugs, propranolol and clonidine, and the other group received double placebo with identical routes of administration. To maintain group balance for this small trial, patients were assigned to treatment groups using a Bayesian weighted 1:1 adaptive co-variate randomization scheme with a random element based on neuroradiologist-rated computed tomography (CT) Marshall Class and age (double-weighted). At 50% accrual, two-stage stopping rules were applied on efficacy with Type I error of 3% and futility with conditional power < 50%.