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

NCT00731627 | Completed Phase 3 DMC

• 2 other identifiers: 2006-000277-30ISRCTN75948817
• Study Type: interventional
• Target: 803
• Locations: 1 country
• Sites: 2

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).

Conditions

Subarachnoid Haemorrhage

Keywords

intracranial aneurysm

Outcome Measures

Primary Outcomes (1)

• Modified Rankin Disability Score (mRS) at 6 months

  6-12 months

Secondary Outcomes (5)

• 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

Study Arms (2)

1

PLACEBO COMPARATOR

placebo

Drug: placebo

11

ACTIVE COMPARATOR

simvastatin

Drug: simvastatin

Interventions

placebo DRUG

one tablet a day for up to 21 days

Also known as: placebo tablet

1

simvastatin DRUG

simvastatin 40mg once a day for a maximum of 21 days

Also known as: ritechol

11

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cambridge University Hospitals NHS Foundation Trust: lead
• British Heart Foundation: collaborator

Study Sites (2)

Dept of Neurological Surgery, University of Florida

Gainesville, Florida, 32610, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Related Publications (1)

• 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.

  PMID: 26181941 DERIVED

MeSH Terms

Conditions

Subarachnoid Hemorrhage; Intracranial Aneurysm

Interventions

Simvastatin

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Intracranial Arterial Diseases; Aneurysm

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant Neurosurgeon

Study Record Dates

• First Submitted: August 7, 2008
• First Posted: August 11, 2008
• Study Start: January 1, 2007
• Primary Completion: September 1, 2013
• Study Completion: February 1, 2014
• Last Updated: June 25, 2014

Record last verified: 2014-06

Locations

US (2)