Simvastatin in Aneurysmal Subarachnoid Haemorrhage (STASH) a Multicentre Randomised Controlled Clinical Trial
Study Details
Study Description
Brief Summary
Intracranial bleeding from ruptured blood vessels (called a subarachnoid haemorrhage -SAH) affects 7000 patients each year in the UK and is a source of considerable death and disability, even in young adults. Recent observations indicate that these bleeds can cause reduced cerebral blood flow which leads to a bad outcome. High rates of death and disability occur, and are particularly prevalent when low cerebral blood flow results in stroke. Prevention of cerebral artery spasm and improvement in blood vessel reflexes are the target of modern therapy. Candidate drugs include statins which have an impeccable safety record and multiple potential beneficial actions (improve cerebral blood flow, reduce inflammatory processes, reduce adverse blood coagulation) following SAH.
The investigators plan to use a statin, Simvastatin (40 mg) to improve cerebral blood flow and reduce inflammation. We have already completed a phase 11 study (n=80) which demonstrated potential benefits for acute statin therapy following SAH, and the investigators now wish to conduct a multi-centre phase 111 study to explore any potential clinical benefits in a larger population (n=1600). The purpose is to see whether the positive effects of statins seen in our phase II study translate into clinical benefits - both short term (e.g. reduced need for intensive care) and long term (outcome and wellbeing at 6 months).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: 1 placebo |
Drug: placebo
one tablet a day for up to 21 days
Other Names:
|
| Active Comparator: 11 simvastatin |
Drug: simvastatin
simvastatin 40mg once a day for a maximum of 21 days
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Modified Rankin Disability Score (mRS) at 6 months [6-12 months]
Secondary Outcome Measures
- Need and intensity of delayed ischaemic deficit rescue therapy [1-3 months]
- Incidence and duration of delayed ischaemic deficits [1-3 months]
- Incidence and severity of sepsis [1-3 months]
- Length of intensive care and total acute hospital stay [1-3 months]
- Discharge destination [1-3 months]
Eligibility Criteria
Criteria
Inclusion Criteria
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Patients (age 18 - 65 yr) in which the admitting neurosurgeon has confirmatory evidence of an aneurysm, either by CT angiography, MR angiography or DSA.
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Any clinical grade accepted provided a reasonable prospect of survival.
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Delay to randomisation and initiation of trial medication from the time of the presenting ictus does not exceed 96 hours.
Exclusion Criteria
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Unsalvageable patients:Fixed and dilated pupils after resuscitation, and/or a devastating scan, which precludes definitive therapy.
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Already taking statin therapy.
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Those taking Warfarin - type drugs.
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Pregnancy.
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Known renal or hepatic impairment
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Suspected or known additional disease process, which threatens life expectancy (e.g.malignancy).
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Known or strong suspicion of drug abuse, alcoholism, or those who are unlikely to be amenable to 6 month follow up.
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Those already taking amiodarone, verapamil or potent CYP3A4 inhibitors.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Dept of Neurological Surgery, University of Florida | Gainesville | Florida | United States | 32610 |
| 2 | Mayo Clinic | Jacksonville | Florida | United States | 32224 |
Sponsors and Collaborators
- Cambridge University Hospitals NHS Foundation Trust
- British Heart Foundation
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2006-000277-30
- ISRCTN75948817