Effects of continuous prostacyclin infusion on regional blood flow and cerebral vasospasm following subarachnoid haemorrhage: 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/DESIGN 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.