Effects of Prostacyclin Infusion on Cerebral Vessels and Metabolism in Patients With Subarachnoid Haemorrhage

Effect of Prostacyclin Infusion on Cerebral Vessels, Cerebral Bloodflow and Cerebral Metabolism in Patients With Subarachnoid Haemorrhage

The purpose of this study is to determine whether prostacyclin is effective in prevention of cerebral vasospasm in patients with subarachnoidal hemorrhage (SAH).

Study Overview

• Status: Completed
• Conditions: Subarachnoid Hemorrhage
• Intervention / Treatment: Drug: Prostacyclin 1 ng/kg/min; Drug: Prostacyclin 2 ng/kg/min; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2200
    • Rigshospitalet, dep. of neurosurgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• SAH verified by CT
• Aneurysm identified and treated
• Fisher grade 3 + 4
• WFNS grade 1-4 (World Federation of Neurosurgical Societies )

Exclusion Criteria:

• Pregnancy/lactation
• Heard failure
• Kidney failure
• Liver failure
• Hemorrhagic diathesis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Continuous i.v. infusion with placebo day 5-10 after SAH
Active Comparator: Low dose prostacyclin	Drug: Prostacyclin 1 ng/kg/min; Continuous i.v. infusion of epoprostenol 1 ng/kg/min day 5-10 after SAH; Other Names: Flolan
Active Comparator: High dose prostacyclin	Drug: Prostacyclin 2 ng/kg/min; Continuous i.v. infusion of epoprostenol 2 ng/kg/min day 5-10 after SAH; Other Names: Flolan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiographic vasospasm measured by CT perfusion	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	Day 8 (+/- 1 day) after aneurysm treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cerebral metabolism measured by microdialysis	Cerebral metabolism measured by microdialysis. Lactate, pyruvate, glucose, glutamate and glycerol are measured.	every 2. hour day 3-10 after aneurysm treatment
Glasgow outcome scale (GOS) at 3 months	Glasgow outcome scale (GOS) at 3 months obtained by telephone interview.	3 months efter SAH
Clinical vasospasm	Clinical vasospasm defined as delayed neurological deficits (DIND).	day 5-10 after SAH
Brain tissue oxygen (PtiO2)	Brain tissue oxygen (PtiO2) measured by Licox catheter.	continuous measurement day 3-10 after SAH
Mean arterial pressure (MAP)	Mean arterial pressure (MAP) measured by arterial catheter.	Continuous day 1-10 after SAH
Radiographic vasospasm measured by CT angiography	Qualitative assessment (none, mild/moderate, severe) of vasospasm.	Measured day 8 +/- 1 day
Level of brain damage biomarker	Serum levels of S100b in peripheral blood	daily day 4-11 after SAH

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuropeptide Y	Neuropeptide Y will be measured in all patients Day 2-11. The concentration will be related to CBF, angiographic vasospasm and clinical outcome for all patients. The results will be reported in a separate puplication.	May 2014

Collaborators and Investigators

• Sponsor: Rune Rasmussen
• Investigators: Principal Investigator: Rune Rasmussen, MD, Rigshospitalet, Denmark

Publications and helpful links

General Publications

• Rasmussen R, Wetterslev J, Stavngaard T, Juhler M, Skjoth-Rasmussen J, Grande PO, Olsen NV. 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.
• Rasmussen R, Juhler M, Wetterslev J. Effects of continuous prostacyclin infusion on regional blood flow and cerebral vasospasm following subarachnoid haemorrhage: statistical analysis plan for a randomized controlled trial. Trials. 2014 Jun 14;15:228. doi: 10.1186/1745-6215-15-228.
• Rasmussen R, Wetterslev J, Stavngaard T, Skjoth-Rasmussen J, Grande PO, Olsen NV, Romner B. The effects of continuous prostacyclin infusion on regional blood flow and cerebral vasospasm following subarachnoid haemorrhage: study protocol for a randomised controlled trial. Trials. 2012 Jul 2;13:102. doi: 10.1186/1745-6215-13-102.

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: October 2, 2011
• First Submitted That Met QC Criteria: October 2, 2011
• First Posted (Estimate): October 5, 2011

Study Record Updates

• Last Update Posted (Estimate): July 21, 2014
• Last Update Submitted That Met QC Criteria: July 18, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: Subarachnoid hemorrhage; vasospasm; prostacyclin
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Hemorrhages; Hemorrhage; Subarachnoid Hemorrhage; Antihypertensive Agents; Vasodilator Agents; Platelet Aggregation Inhibitors; Epoprostenol; Tezosentan
• Other Study ID Numbers: 2011-002798-50