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

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

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.

Study Overview

• Status: Terminated
• Conditions: Aneurysmal Subarachnoid Hemorrhage; Cerebral Vasospasm
• Intervention / Treatment: Drug: Placebo; Drug: Simvastatin 40 mg; Drug: Simvastatin 80 mg

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Univeristy of Illinois at Chicago, Dept of Neurosurgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: University of Illinois at Chicago
• Investigators: Principal Investigator: Ben Z. Roitberg, MD, Assnt Prof. Univ. of Illinois at Chicago, Dept of Neurosurgery; Principal Investigator: Ali Alaraj, MD, Clinical Fellow Department of Neurosurgery

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Actual): February 1, 2009
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: June 15, 2007
• First Submitted That Met QC Criteria: June 15, 2007
• First Posted (Estimate): June 18, 2007

Study Record Updates

• Last Update Posted (Estimate): November 25, 2015
• Last Update Submitted That Met QC Criteria: October 22, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: SAH; Vasospasm
• 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; Vasospasm, Intracranial; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin
• Other Study ID Numbers: 2005-0857