Clinical trial NCT00731627: Simvastatin in Aneurysmal Subarachnoid Haemorrhage (STASH) a Multicentre Randomised Controlled Clinical Trial
Official title: Simvastatin in Aneurysmal Subarachnoid Haemorrhage (STASH) a Multicentre Randomised Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Subarachnoid Haemorrhage
Keywords: intracranial aneurysm
Lead sponsor: Cambridge University Hospitals NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: British Heart Foundation
First posted: 2008-08-11
Enrollment: 803
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Modified Rankin Disability Score (mRS) at 6 months
timeFrame: 6-12 months
Secondary outcomes:
measure: Need and intensity of delayed ischaemic deficit rescue therapy
timeFrame: 1-3 months
measure: Incidence and duration of delayed ischaemic deficits
timeFrame: 1-3 months
measure: Incidence and severity of sepsis
timeFrame: 1-3 months
measure: Length of intensive care and total acute hospital stay
timeFrame: 1-3 months
measure: Discharge destination
timeFrame: 1-3 months
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: Dept of Neurological Surgery, University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
Study officials:
References:
citation: Budohoski KP, Czosnyka M, Kirkpatrick PJ. The Role of Monitoring Cerebral Autoregulation After Subarachnoid Hemorrhage. Neurosurgery. 2015 Aug;62 Suppl 1:180-4. doi: 10.1227/NEU.0000000000000808. No abstract available.