Effect of simvastatin on endothelial dysfunction, fibrinolysis, coagulation and inflammation after aneurysmal subarachnoid hemorrhage

ISRCTN	ISRCTN45662651
DOI	https://doi.org/10.1186/ISRCTN45662651
Protocol serial number	NTR668
Sponsor	Academic Medical Centre (AMC) (The Netherlands)
Funder	Academic Medical Centre (AMC) (Netherlands) - Department of Neurology

Submission date: 29/06/2006
Registration date: 29/06/2006
Last edited: 02/09/2009

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nervous System Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr M.D.I. Vergouwen
Scientific

Academisch Medisch Centrum
Afdeling Neurologie H2
Meibergdreef 9
Amsterdam
1105 AZ
Netherlands

Phone	+31 (0)20 5663842
Email	m.d.vergouwen@amc.uva.nl

Study information

Primary study design	Interventional
Study design	Randomised doube blind placebo controlled parallel group trial
Secondary study design	Randomised controlled trial
Scientific title
Study objectives	In patients with aneurysmal subarachnoid hemorrhage (SAH), simvastatin restores endothelial cell damage, activates fibrinolysis, and improves coagulation and inflammation after the hemorrhage.
Ethics approval(s)	Received from local medical ethics committee
Health condition(s) or problem(s) studied	Aneurysmal subarachnoid hemorrhage
Intervention	Patients will receive simvastatin 80 mg a day or placebo until day 14 after aneurysmal subarachnoid hemorrhage.
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Simvastatin
Primary outcome measure(s)	1. The effects of simvastatin on the parameters of fibrinolysis, coagulation, inflammation and endothelial function after SAH 2. The relation between changes in fibrinolytic activity and endothelial cell damage and activation
Key secondary outcome measure(s)	1. The occurrence of cerebral ischemia after SAH 2. Outcome on the Glasgow Outcome Scale and Academic Medical Center Linear Disability Scale (ALDS) three and six months after subarachnoid hemorrhage 3. The relation between vasospasm as observed on transcranial Doppler examination and parameters of fibrinolysis, coagulation, endothelium dysfunction and inflammation 4. The relationship between cerebral ischemia as observed on perfusion CT-scans and parameters of fibrinolysis, coagulation, endothelium dysfunction and inflammation 5. The relationship between plasminogen activator inhibitor type-1(PAI-1) polymorphism and fibrinolysis in patients treated with simvastatin and placebo 6. The relationship of polymorphisms in the endothelin system on endothelial cell damage 7. Differences in cerebral microcirculation between patients treated with placebo and simvastatin
Completion date	01/11/2007

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	30
Key inclusion criteria	1. Patients with clinical symptoms and signs of SAH with an aneurysmal bleeding pattern on the initial computerised tomography (CT) scan. CT scan has to be performed within 48 hours after SAH onset 2. Patients with a perimesencephalic hemorrhage pattern on the initial CT scan while computed tomographic angiography (CTA) or conventional angiography has shown an appropriate aneurysm. CTA or angiography has to be performed within 48 hours after SAH onset 3. If CT scan is negative while there is evidence of bleeding in the cerebrospinal fluid (xanthochromia) and the CT-angiography has shown an aneurysm
Key exclusion criteria	1. Under 18 years of age 2. A time lapse of more than 48 hours after SAH onset 3. Patients using aspirin or warfarin 4. Patients already using statins 5. Contra-indication for simvastatin (active liver disease, liver transaminase more than three times the normal upper limit, myopathy) 6. Kidney insufficiency 7. If death appears imminent 8. Pregnancy or lactation
Date of first enrolment	01/05/2006
Date of final enrolment	01/11/2007

Locations

Countries of recruitment

Netherlands

Study participating centre

Academisch Medisch Centrum

Amsterdam
1105 AZ
Netherlands

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/08/2009		Yes	No