Effects of prostacyclin on cerebral blood flow and vasospasm after subarachnoid hemorrhage: randomized, pilot trial

Stroke. 2015 Jan;46(1):37-41. doi: 10.1161/STROKEAHA.114.007470. Epub 2014 Nov 20.

Abstract

Background and purpose: Delayed ischemic neurological deficits (DINDs) are a major contributing factor for poor outcome in patients with subarachnoid hemorrhage. In this trial, we investigated the therapeutic potential of prostacyclin, an endogen substance with known effect on vascular tone and blood flow regulation, on factors related to DIND.

Methods: This trial is a single-center, randomized, blinded, clinical, pilot trial with 3 arms. Ninety patients were randomized to continuous infusion of prostacyclin 1 ng/kg per minute, prostacyclin 2 ng/kg per minute, or placebo. The intervention was initiated day 5 after subarachnoid hemorrhage and discontinued day 10. Primary outcome was the difference in change from baseline in global cerebral blood flow. Secondary outcome measures were occurrence of DIND, angiographic vasospasm, and clinical outcome at 3 months.

Results: No statistically significant difference in change of global cerebral blood flow was found between the intervention groups. The observed incidence of DIND and angiographic vasospasm was markedly higher in the placebo group, although this difference was not statistically significant. No statistically significant differences in safety parameters or clinical outcome were found between the 3 groups.

Conclusions: Administration of prostacyclin to patients with subarachnoid hemorrhage may be safe and feasible. Global cerebral blood flow after subarachnoid hemorrhage is not markedly affected by administration of prostacyclin in the tested dose range. It may be possible that the observed reduction in the point estimates of DIND and vasospasm in the prostacyclin groups represents an effect of prostacyclin as this trial was not powered to investigate the effect of prostacyclin on these outcomes.

Clinical trial registration url: http://www.clinicaltrials.gov. Unique identifier: NCT01447095.

Keywords: epoprostenol; subarachnoid hemorrhage; vasospasm, intracranial.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antihypertensive Agents / pharmacology
  • Antihypertensive Agents / therapeutic use*
  • Brain Ischemia / diagnostic imaging
  • Brain Ischemia / prevention & control*
  • Cerebral Angiography
  • Cerebrovascular Circulation / drug effects*
  • Epoprostenol / pharmacology
  • Epoprostenol / therapeutic use*
  • Female
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Perfusion Imaging
  • Pilot Projects
  • Subarachnoid Hemorrhage / diagnostic imaging
  • Subarachnoid Hemorrhage / drug therapy*
  • Tomography, X-Ray Computed
  • Treatment Outcome
  • Vasospasm, Intracranial / diagnostic imaging
  • Vasospasm, Intracranial / prevention & control*
  • Young Adult

Substances

  • Antihypertensive Agents
  • Epoprostenol

Associated data

  • ClinicalTrials.gov/NCT01447095