The effects of continuous prostacyclin infusion on regional blood flow and cerebral vasospasm following subarachnoid haemorrhage: study protocol for a randomised controlled trial

TY - JOUR

T1 - The effects of continuous prostacyclin infusion on regional blood flow and cerebral vasospasm following subarachnoid haemorrhage

T2 - study protocol for a randomised controlled trial

AU - Rasmussen, Rune

AU - Wetterslev, Jørn

AU - Stavngaard, Trine

AU - Skjøth-Rasmussen, Jane

AU - Grände, Per Olof

AU - Olsen, Niels Vidiendal

AU - Romner, Bertil

PY - 2012/7/2

Y1 - 2012/7/2

N2 - Background: One of the main causes of mortality and morbidity following subarachnoid haemorrhage (SAH) is the development of cerebral vasospasm, a frequent complication arising in the weeks after the initial bleeding. Despite extensive research, to date no effective treatment of vasospasm exists. 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 randomised, clinical trials have been conducted, investigating the possible pharmacodynamic effects of prostacyclin on the human brain following SAH.Methods: This trial is a single-centre, randomised, placebo-controlled, parallel group, blinded, clinical, pilot trial. A total of 90 patients with SAH will be randomised to one of three intervention arms: epoprostenol 1 ng/kg/min, epoprostenol 2 ng/kg/min or placebo in addition to standard treatment. Trial medication will start day 5 after SAH and continue to day 10. The primary outcome measure is changes in regional cerebral blood flow from baseline in the arterial territories of the anterior cerebral artery, medial cerebral artery and the posterior cerebral artery, measured by CT perfusion scan. The secondary outcomes will be vasospasm measured by CT angiography, ischaemic parameters measured by brain microdialysis, flow velocities in the medial cerebral artery, clinical parameters and outcome (Glasgow Outcome Scale) at 3 months.Trial registration: Clinicaltrials.gov NCT01447095.

AB - Background: One of the main causes of mortality and morbidity following subarachnoid haemorrhage (SAH) is the development of cerebral vasospasm, a frequent complication arising in the weeks after the initial bleeding. Despite extensive research, to date no effective treatment of vasospasm exists. 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 randomised, clinical trials have been conducted, investigating the possible pharmacodynamic effects of prostacyclin on the human brain following SAH.Methods: This trial is a single-centre, randomised, placebo-controlled, parallel group, blinded, clinical, pilot trial. A total of 90 patients with SAH will be randomised to one of three intervention arms: epoprostenol 1 ng/kg/min, epoprostenol 2 ng/kg/min or placebo in addition to standard treatment. Trial medication will start day 5 after SAH and continue to day 10. The primary outcome measure is changes in regional cerebral blood flow from baseline in the arterial territories of the anterior cerebral artery, medial cerebral artery and the posterior cerebral artery, measured by CT perfusion scan. The secondary outcomes will be vasospasm measured by CT angiography, ischaemic parameters measured by brain microdialysis, flow velocities in the medial cerebral artery, clinical parameters and outcome (Glasgow Outcome Scale) at 3 months.Trial registration: Clinicaltrials.gov NCT01447095.

KW - Cerebral Angiography

KW - Cerebral Arteries

KW - Cerebrovascular Circulation

KW - Denmark

KW - Epoprostenol

KW - Glasgow Coma Scale

KW - Humans

KW - Infusions, Parenteral

KW - Microdialysis

KW - Perfusion Imaging

KW - Pilot Projects

KW - Regional Blood Flow

KW - Research Design

KW - Subarachnoid Hemorrhage

KW - Time Factors

KW - Tomography, X-Ray Computed

KW - Treatment Outcome

KW - Vasoconstriction

KW - Vasodilator Agents

KW - Vasospasm, Intracranial

U2 - 10.1186/1745-6215-13-102

DO - 10.1186/1745-6215-13-102

M3 - Journal article

C2 - 22747768

SN - 1745-6215

VL - 13

SP - 1

EP - 6

JO - Trials

JF - Trials

M1 - 102

ER -