Simvastatin in Aneurysmal Subarachnoid Haemorrhage (STASH) a Multicentre Randomised Controlled Clinical Trial

Study Overview
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Brief Summary
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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).

Official Title
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Simvastatin in Aneurysmal Subarachnoid Haemorrhage (STASH) a Multicentre Randomised Controlled Clinical Trial

Conditions
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Subarachnoid Haemorrhage

Intervention / Treatment
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* Drug: placebo
* Drug: simvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Patients (age 18 - 65 yr) in which the admitting neurosurgeon has confirmatory evidence of an aneurysm, either by CT angiography, MR angiography or DSA. Any clinical grade accepted provided a reasonable prospect of survival. Delay to randomisation and initiation of trial medication from the time of the presenting ictus does not exceed 96 hours. Exclusion Criteria Unsalvageable patients:Fixed and dilated pupils after resuscitation, and/or a devastating scan, which precludes definitive therapy. Already taking statin therapy. Those taking Warfarin - type drugs. Pregnancy. Known renal or hepatic impairment Suspected or known additional disease process, which threatens life expectancy (e.g.malignancy). Known or strong suspicion of drug abuse, alcoholism, or those who are unlikely to be amenable to 6 month follow up. Those already taking amiodarone, verapamil or potent CYP3A4 inhibitors.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br>placebo | Drug: placebo<br>* one tablet a day for up to 21 days<br>* Other names: placebo tablet;|
| Active Comparator: 11<br>simvastatin | Drug: simvastatin<br>* simvastatin 40mg once a day for a maximum of 21 days<br>* Other names: ritechol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Rankin Disability Score (mRS) at 6 months |  | 6-12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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intracranial aneurysm