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

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).

Study Overview

• Status: Completed
• Conditions: Subarachnoid Haemorrhage
• Intervention / Treatment: Drug: placebo; Drug: simvastatin

• Study Type: Interventional
• Enrollment (Actual): 803
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • Dept of Neurological Surgery, University of Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Cambridge University Hospitals NHS Foundation Trust
• Collaborators: British Heart Foundation

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): September 1, 2013
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: August 7, 2008
• First Submitted That Met QC Criteria: August 7, 2008
• First Posted (Estimate): August 11, 2008

Study Record Updates

• Last Update Posted (Estimate): June 25, 2014
• Last Update Submitted That Met QC Criteria: June 24, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: intracranial aneurysm
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Hemorrhages; Hemorrhage; Subarachnoid Hemorrhage; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin
• Other Study ID Numbers: 2006-000277-30; ISRCTN75948817