Use of Simvastatin for the Prevention of Vasospasm in Aneurysmal Subarachnoid Hemorrhage

Study Overview
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Brief Summary
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The purpose of this study is to test whether treatment with a drug called Simvastatin prevents and improves outcome in patients who have Subarachnoid bleeding. Simvastatin is currently approved for the treatment of high cholesterol levels.

Detailed Description
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Aneurysmal Subarachnoid hemorrhage or SAH (bleeding on the surface of the brain) affects 10 per 100,000 population each year. For survivors of the initial hemorrhage, delayed narrowing of the blood vessels (vasospasm) and related delayed strokes are the most common serious complication. Narrowing of blood vessels affect 30% of patients with such bleeding. Despite maximum therapy, nearly 50% of patients with symptomatic vasospasm with develop stroke. Because cerebral vasospasm remains the leading cause of morbidity and mortality after aSAH, this critically important issue needs further studies. One hundred and fifty patients will be randomized, 50 to each arm of the study. Patients enrolled in the study will be receive the drug (either Simvastatin 40 mg or Simvastatin 80 mg per mouth daily), while the control group will receive a sugar tablet. The treatment will be continued for a total of 21 days. The neurological abilities (Stroke Outcome measures, these are included with the application for your review) at day 21 post aSAH will be reviewed at time of discharge as well at 6 months of follow up.

Official Title
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Randomized Double Blind Study Using Simvastatin for the PRevention Aof Vasospasm in Aneurysmal Subarachnoid Hemorrhage

Conditions
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Aneurysmal Subarachnoid Hemorrhage, Cerebral Vasospasm

Intervention / Treatment
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* Drug: Simvastatin 40 mg
* Drug: Placebo
* Drug: Simvastatin 80 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-85 years old inclusive Subarachnoid hemorrhage diagnosed by CT on admission Randomizable within 732 hours of subarachnoid hemorrhage Saccular intracranial aneurysm proven by cerebral angiography or computed tomographic angiography (CTA) Surgical or endovascular obliteration Able to obtain written informed consent from patient or surrogate Exclusion Criteria: Pregnancy, as confirmed by routine urine test on admission Elevated liver function test at time of randomization, defined as more than three times the upper limit of normal On Statins, niacin, or fibrate therapy within 30 days of presentation Any vasospasm on the initial diagnostic angiogram Glasgow Coma Scale 5 or less at the time of randomization History of liver disease or active liver disease Hypersensitivity to statins Patient taking medication not recommended for concomitant use with Simvastatin (40 or 80 mg) as per the product label

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control Group<br>Placebo tablet | Drug: Placebo<br>* Placebo tablet<br>* Other names: dummy pill, sugar pill;|
| Experimental: Study Group #1<br>Simvastatin 40 mg | Drug: Simvastatin 40 mg<br>* Comparing two doses of Simvastatin to placebo<br>* Other names: Zocor;|
| Experimental: Study Group #2<br>Simvastatin 80 mg | Drug: Simvastatin 80 mg<br>* Comparing two doses of Simvastatin to placebo<br>* Other names: Zocor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Measure Outcome in Patients Diagnosed With Aneurysmal Subarachnoid Hemorrhage (aSAH) Treated With Simvastatin, by Assessing Neurological Outcome by Accessing Glasgow Outcome Score, Modified Rankin Scale, and Barthel Index Score at Day 21 Post aSAH |  | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Determine Efficiency of Simvastatin in Decreasing the Incidence of Clinical Vasospasm in aSAH, and Define the Optimal Dose of Simvastatin and to Measure Outcome at 6 Months Follow up | Study PI left before the efficacy of Simvastatin decreasing the incidence of clinical vasospasm in aSAH, and defining the optimal dose of Simvastatin and measuring the outcome at 6 months follow up data was collected for the study and therefore these outcomes will never be analyzed. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vasospasm, SAH