Contact information
Type
Scientific
Primary contact
Dr M.D.I. Vergouwen
ORCID ID
Contact details
Academisch Medisch Centrum
Afdeling Neurologie H2
Meibergdreef 9
Amsterdam
1105 AZ
Netherlands
+31 (0)20 5663842
m.d.vergouwen@amc.uva.nl
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
NTR668
Study information
Scientific title
Acronym
Study hypothesis
In patients with aneurysmal subarachnoid hemorrhage (SAH), simvastatin restores endothelial cell damage, activates fibrinolysis, and improves coagulation and inflammation after the hemorrhage.
Ethics approval
Received from local medical ethics committee
Study design
Randomised doube blind placebo controlled parallel group trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
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 names
Simvastatin
Primary outcome measures
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
Secondary outcome measures
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
Overall trial start date
01/05/2006
Overall trial end date
01/11/2007
Reason abandoned
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
30
Participant 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
Recruitment start date
01/05/2006
Recruitment end date
01/11/2007
Locations
Countries of recruitment
Netherlands
Trial participating centre
Academisch Medisch Centrum
Amsterdam
1105 AZ
Netherlands
Funders
Funder type
University/education
Funder name
Academic Medical Centre (AMC) (Netherlands) - Department of Neurology
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
2009 results in http://www.ncbi.nlm.nih.gov/pubmed/19458605
Publication citations
-
Results
Vergouwen MD, Meijers JC, Geskus RB, Coert BA, Horn J, Stroes ES, van der Poll T, Vermeulen M, Roos YB, Biologic effects of simvastatin in patients with aneurysmal subarachnoid hemorrhage: a double-blind, placebo-controlled randomized trial., J. Cereb. Blood Flow Metab., 2009, 29, 8, 1444-1453, doi: 10.1038/jcbfm.2009.59.