Simvastatin in aneurysmal subarachnoid haemorrhage: a multicentre, randomised controlled, clinical phase III study

ISRCTN ISRCTN75948817
DOI https://doi.org/10.1186/ISRCTN75948817
EudraCT/CTIS number 2006-000277-30
ClinicalTrials.gov number NCT00731627
Secondary identifying numbers STASH01
Submission date
15/02/2006
Registration date
04/04/2006
Last edited
12/08/2014
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Circulatory System
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Background and study aims.
A blood vessel abnormality called an aneurysm can cause a bleed within the head. We wish to study the potential benefits of giving a standard cholesterol lowering drug (called Simvastatin) after a bleed has occurred. This is a licensed medication used regularly in the treatment for other vascular conditions including heart attacks and strokes, but it is not licensed at this stage for the treatment of a bleed in the brain. In some instances we may also wish to find out whether the patient’s genetic makeup can influence the course of your disease, its clinical outcome, or response to the medicine that we are testing.

Who can participate?
Patients aged 18 – 65years in whom the admitting neurosurgeon has diagnosed a bleed onto the surface of the brain, called a subarachnoid haemorrhage (SAH). We propose to recruit approximately 800 people to the trial.

What does the study involve?
Patients will be allocated randomly (like a flip of the coin) to taking either Simvastatin 40mg or an inactive “dummy” drug called a placebo. The treatment will be administered as one tablet daily for up to 21 days. If the patient is discharged from the Neurosurgical Unit before 21 days, treatment will be stopped. Nobody (not even the doctors) will know which treatment is being given until the study is over. However, if necessary, the doctor will be able to find out which treatment has been given if any concern arises. Before they leave the hospital we will assess the patient’s level of recovery. Two short questionnaires will be sent to their home 6 months later asking about their current level of recovery and state of health.

What are the possible benefits and risks of participating?
In the event of taking Simvastatin we hope that this drug might help in recovery. However, this cannot be guaranteed. More likely, the information we obtain from this study may help us to improve on the treatment for future patients suffering from SAH.
Possible rare side effects of Simvastatin include muscle weakness or tenderness, headache, nausea or rash. However no regular side effects have been observed even in patients receiving this treatment for many years. However, in the event of any serious unforeseen reactions, or if any concerns arise, the drug will be stopped immediately.

Where is the study run from?
Department of Neurosurgery, Cambridge University Hospitals NHS Foundation Trust

When is the study starting and how long is it expected to run for?
The study started in May 2006 and is expected to end in January 2014.

Who is funding the study?
British Heart Foundation

Who is the main contact?
Mr Peter J Kirkpatrick
pjk21@medschl.cam.ac.uk

Study website

Contact information

Mr Peter Kirkpatrick
Scientific

Box 167
Addenbrooke's Hospital
Hills Road
Cambridge
CB2 2QQ
United Kingdom

Study information

Study designMulti-centre double-blind randomised controlled trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet http://www.stashtrial.com/downloads.html
Scientific title
Study acronymSTASH
Study objectivesCan acute statin therapy reduce the incidence and duration of delayed ischaemic deficits following a subarachnoid haemorrhage (SAH)?

On 04/12/2012 the anticipated end date was changed from 01/05/2009 to 31/01/2014.
Ethics approval(s)Thames Valley Research Ethics Committee, 06/07/2006, ref: 06/MRE12/26
Health condition(s) or problem(s) studiedSubarachnoid haemorrhage
InterventionSimvastatin versus placebo
Intervention typeDrug
Pharmaceutical study type(s)
PhasePhase III
Drug / device / biological / vaccine name(s)Simvastatin
Primary outcome measureClinical outcome at six months
Secondary outcome measures1. Short form questionnaire (SF-36) scores at six months
2. Incidence and duration of delayed ischaemic deficits
3. Need and intensity of delayed ischaemic deficits rescue therapy
4. Incidence of extracranial organ dysfunction and failure
5. Incidence and duration of extracranial organ support
6. Incidence and severity of sepsis
7. Length of intensive care and total acute hospital stay
8. Percentage of patients being discharged directly home
9. Reduction in intensive care requirements for those with sepsis
Overall study start date01/05/2006
Completion date31/01/2014

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
Upper age limit65 Years
SexBoth
Target number of participants800
Key inclusion criteria1. Patients aged 18-65 years
2. If the admitting neurosurgeon has a high index of suspicion of a spontaneous aneurysmal subarachnoid haemorrhage (good clinical history with convincing computerised tomography [CT] findings)
3. Any clinical grade accepted provided there is a reasonable prospect of survival
4. Delay to randomisation and initiation of trial medication, from the time of the presenting bleed, does not exceed 96 hours
5. Independent prior to the SAH
Key exclusion criteria1. Unsalvageable patients: fixed and dilated pupils after resuscitation, and/or a devastating scan, which precludes definitive therapy
2. Already taking statin therapy
3. Those taking warfarin-type drugs
4. Pregnancy
5. Known renal or hepatic impairment
6. Suspected or known additional disease process, which threatens life expectancy (e.g. malignancy)
7. Known or strong suspicion of drug abuse, alcoholism, or those who are unlikely to be amenable to six-month follow up
Date of first enrolment01/05/2006
Date of final enrolment31/01/2014

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

Box 167
Cambridge
CB2 2QQ
United Kingdom

Sponsor information

Cambridge University Hospitals NHS Foundation Trust (UK)
Hospital/treatment centre

Box 146
Addenbrooke's Hospital
Hills Road
Cambridge
CB2 2QQ
England
United Kingdom

ROR logo "ROR" https://ror.org/04v54gj93

Funders

Funder type

Charity

British Heart Foundaton (BHF) (UK)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 01/07/2014 Yes No