Statins and Cerebral Blood Flow in Subarachnoid Hemorrhage (SAH)

Study Overview
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Brief Summary
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The primary objective of this project is to investigate the effect of statin therapy on cerebral blood flow in patients with aneurysmal SAH who are randomized to receive or not receive statins in a blinded design.

Detailed Description
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We will determine if statin therapy improves CBF in patients with aneurysmal subarachnoid hemorrhage. This improvement, if present, may be due to improved basal CBF, improved autoregulatory function, or a mitigation of large arterial narrowing. The information gain from this study will help us to better understand the mechanism of action of statins. This knowledge may be useful in the design of future studies with statins and in the development of other therapies aimed at similar mechanisms.

Official Title
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Effect of Statins on Cerebral Blood Flow After Subarachnoid Hemorrhage

Conditions
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Subarachnoid Hemorrhage

Intervention / Treatment
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* Drug: Simvastatin, 80 mg/day for 21 days
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 SAH from ruptured cerebral aneurysm within 48 hours of admission. Modified Fisher grade 2,3,or 4 Planned surgical or endovascular aneurysm repair Exclusion Criteria: Pregnancy SAH secondary to traumatic or mycotic aneurysms Pre-ictal statin therapy Contraindication to stain therapy WFNS grade 5 Contraindications to MAP elevation on day 7-10

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Simvastatin, 80 mg/day<br>Simvastatin, 80 mg/day for 21 days | Drug: Simvastatin, 80 mg/day for 21 days<br>* Active treatment group<br>* Other names: Simvastatin;|
| Placebo Comparator: Placebo<br>Placebo | Drug: placebo<br>* Control group<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resting Cerebral Blood Flow During Peak Period of Vasospasm Risk | Resting cerebral blood flow during peak period of vasospasm risk measured by PET | 7-10 days after hemorrhage | 
| Cerebral Autoregulation During Peak Period of Vasospasm Risk | Fraction of patients with impaired static autoregulation (% change in MAP/% change in CVR) * 100 A value of <60 is considered abnormal. | 7-10 days after hemorrhage | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of Statin on Oxygen Extraction Fraction and Cerebral Metabolism During Peak Period of Vasospasm Risk | Oxygen extraction fraction (OEF) is the ratio of Oxygen delivery (ml/100 g/min) and oxygen utilization (ml/100 g/min). It describes the fraction of the oxygen that reaches the brain that it actually uses for energy production. | 7-10 days after hemorrhage | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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subarachnoid hemorrhage, vasospasm, cerebral blood flow, cerebral metabolism, autoregulation, statin, Vasospasm associated with Subarachnoid hemorrhage