Subarachnoid Haemorrhage
Conditions
Keywords
intracranial aneurysm
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).
Interventions
DRUGplacebo
one tablet a day for up to 21 days
DRUGsimvastatin
simvastatin 40mg once a day for a maximum of 21 days
Sponsors
British Heart Foundation
Cambridge University Hospitals NHS Foundation Trust
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Modified Rankin Disability Score (mRS) at 6 months | 6-12 months |
Secondary
| Measure | 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 |
Countries
United States
Outcome results
None listed