Simvastatin in Aneurysmal Subarachnoid Haemorrhage (STASH) a Multicentre Randomised Controlled Clinical Trial - Full Text View

Purpose

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	Intervention	Phase
Subarachnoid Haemorrhage	Drug: placebo Drug: simvastatin	Phase III

Drug Information available for:

Simvastatin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment

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

Further study details as provided by Cambridge University Hospitals NHS Foundation Trust:

Primary Outcome Measures:

Modified Rankin Disability Score (mRS) at 6 months [ Time Frame: at 6months post ictus ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Need and intensity of delayed ischaemic deficit rescue therapy [ Time Frame: during in-patient stay ] [ Designated as safety issue: No ]
Incidence and duration of delayed ischaemic deficits [ Time Frame: during in-patient stay ] [ Designated as safety issue: No ]
incidence and severity of sepsis [ Time Frame: during ip-patient stay ] [ Designated as safety issue: No ]
Length of intensive care and total acute hospital stay [ Time Frame: during ip-patient stay ] [ Designated as safety issue: No ]
discharge destination [ Time Frame: on discharge from hospital ] [ Designated as safety issue: No ]

Estimated Enrollment:	1600
Study Start Date:	January 2007
Estimated Primary Completion Date:	June 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Placebo Comparator placebo	Drug: placebo one tablet a day for up to 21 days
11: Active Comparator simvastatin	Drug: simvastatin simvastatin 40mg once a day for a maximum of 21 days

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00731627

Contacts


Contact: Peter J Kirkpatrick, FRCS	+44 1223 217214	pjk21@medschl.cam.ac.uk

Contact: Carole L Turner, MSc	+44 1223 217205	clt29@medschl.cam.ac.uk

Locations


United States, Florida
	Dept of Neurological Surgery, University of Florida	Recruiting
	Gainesville, Florida, United States, 32610
	Contact: Stephen Lewis, FRACS 352-273-9000 stephen.lewis@neurosurgery.ufl.edu
	Contact: Lynn Miralia 352 273 5680 miralia@neurosurgery.ufl.edu
	Principal Investigator: Stephen Lewis, FRACS

Sponsors and Collaborators

Cambridge University Hospitals NHS Foundation Trust

British Heart Foundation

More Information

Responsible Party:	R and D Director, Addenbrooke's Hospital ( Dr Bradley/Cambridge University Hospitals NHS Foundation Trust )
Study ID Numbers:	2006-000277-30, ISRCTN75948817
First Received:	August 7, 2008
Last Updated:	August 7, 2008
ClinicalTrials.gov Identifier:	NCT00731627
Health Authority:	United States: Food and Drug Administration

Keywords provided by Cambridge University Hospitals NHS Foundation Trust:

intracranial aneurysm

Study placed in the following topic categories:

Intracranial Aneurysm

Aneurysm

Simvastatin

Vascular Diseases

Subarachnoid Hemorrhage

Central Nervous System Diseases

Intracranial Hemorrhages

Brain Diseases

Hemorrhage

Cerebrovascular Disorders

Additional relevant MeSH terms:

Antimetabolites

Pathologic Processes

Molecular Mechanisms of Pharmacological Action

Therapeutic Uses

Antilipemic Agents

Nervous System Diseases

Enzyme Inhibitors

Cardiovascular Diseases

Anticholesteremic Agents

Hydroxymethylglutaryl-CoA Reductase Inhibitors

Pharmacologic Actions

ClinicalTrials.gov processed this record on October 31, 2008

Sponsors and Collaborators:	Cambridge University Hospitals NHS Foundation Trust British Heart Foundation
Information provided by:	Cambridge University Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier:	NCT00731627