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

This study has been completed.
Sponsor:
Collaborator:
British Heart Foundation
Information provided by (Responsible Party):
Mr PJ Kirkpatrick, Cambridge University Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT00731627
First received: August 7, 2008
Last updated: June 24, 2014
Last verified: June 2014
  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 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Simvastatin in Aneurysmal Subarachnoid Haemorrhage (STASH) a Multicentre Randomised Controlled Clinical Trial

Resource links provided by NLM:


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: 6-12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Need and intensity of delayed ischaemic deficit rescue therapy [ Time Frame: 1-3 months ] [ Designated as safety issue: No ]
  • Incidence and duration of delayed ischaemic deficits [ Time Frame: 1-3 months ] [ Designated as safety issue: No ]
  • Incidence and severity of sepsis [ Time Frame: 1-3 months ] [ Designated as safety issue: No ]
  • Length of intensive care and total acute hospital stay [ Time Frame: 1-3 months ] [ Designated as safety issue: No ]
  • Discharge destination [ Time Frame: 1-3 months ] [ Designated as safety issue: No ]

Enrollment: 803
Study Start Date: January 2007
Study Completion Date: February 2014
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 1
placebo
Drug: placebo
one tablet a day for up to 21 days
Other Name: placebo tablet
Active Comparator: 11
simvastatin
Drug: simvastatin
simvastatin 40mg once a day for a maximum of 21 days
Other Name: ritechol

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, Florida
Dept of Neurological Surgery, University of Florida
Gainesville, Florida, United States, 32610
Mayo Clinic
Jacksonville, Florida, United States, 32224
Sponsors and Collaborators
Cambridge University Hospitals NHS Foundation Trust
British Heart Foundation
  More Information

No publications provided

Responsible Party: Mr PJ Kirkpatrick, Consultant Neurosurgeon, Cambridge University Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT00731627     History of Changes
Other Study ID Numbers: 2006-000277-30, ISRCTN75948817
Study First Received: August 7, 2008
Last Updated: June 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Cambridge University Hospitals NHS Foundation Trust:
intracranial aneurysm

Additional relevant MeSH terms:
Hemorrhage
Subarachnoid Hemorrhage
Intracranial Hemorrhages
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Pathologic Processes
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Simvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014