statistical analysis plan for a randomized controlled trial
BACKGROUND: One of the main causes of mortality and morbidity following subarachnoid hemorrhage (SAH) is the development of cerebral vasospasm, a frequent complication arising in the weeks after the initial bleeding. Despite extensive research, no effective treatment of vasospasm exists to date. Prostacyclin is a potent vasodilator and inhibitor of platelet aggregation. In vitro models have shown a relaxing effect of prostacyclin after induced contraction in cerebral arteries, and a recent pilot trial showed a positive effect on cerebral vasospasm in a clinical setting. No randomized clinical trials have investigated the possible pharmacodynamic effects of prostacyclin on the human brain following SAH. METHODS: This trial is a single centre, randomized, placebo-controlled, parallel group, double blinded, clinical pilot trial. A total of 90 patients with SAH will be randomized to one of three intervention arms: epoprostenol at 1 ng/kg/min, epoprostenol at 2 ng/kg/min, or placebo in addition to the standard treatment. Trial medication will start on Day 5 after SAH and continue to Day 10. The primary outcome measure is changes in cerebral blood flow measured by a computed tomography (CT) perfusion scan. The secondary outcomes are vasospasm measured by a CT angiography, regional blood flow, clinical symptoms of cerebral ischemia, and outcome at three months (Glasgow Outcome Scale). DISCUSSION: The primary outcome has been altered slightly since the publication of our study protocol. Global cerebral blood flow is now primary outcome, whereas regional blood flow is a secondary outcome.Trial registration: Clinicaltrials.gov NCT01447095. Registration date: 11 October 2011.
Trials, 2014, Vol 15, Issue 1
Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't