Condition category
Circulatory System
Date applied
24/04/2013
Date assigned
25/04/2013
Last edited
07/05/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
Recruiting

Plain English Summary

Background and study aims
More than one third of the adults with a stroke due to bleeding into the brain - known as brain haemorrhage - are taking drugs to prevent clotting when they have a brain haemorrhage. These patients had previously suffered illnesses like angina, heart attack, or stroke due to blood vessel blockage, which is why they are treated with drugs to prevent further clots occurring. These drugs are usually stopped when the brain haemorrhage occurs. But when patients recover from brain haemorrhage, they and their doctors are often uncertain about whether to restart these drugs to prevent further clots occurring, or whether to avoid them in case they increase the risk of brain haemorrhage happening again. We will study the potentially beneficial effects of three antiplatelet drugs (aspirin, clopidogrel, or dipyridamole) on the risks of heart attack, stroke and other clotting problems as well as their effect on the risk of a brain haemorrhage happening again. This information will help us to decide whether antiplatelet drugs are a promising treatment. If they are, we will recruit a much larger number of patients so that we can determine really reliably whether the beneficial effects of antiplatelet drugs on the risk of clotting outweigh any risks of a repeat brain haemorrhage for such people.

Who can participate?
We aim to recruit 720 men and women in the UK aged 18 years or more who survive a brain haemorrhage. If participants are unable to provide fully informed consent a relative or other legal representative may be approached for their consent.

What does the study involve?
Research staff will collect baseline information about each participant. Some participants may also have an additional MRI scan. Participants will be randomly allocated to either start or avoid antiplatelet medication. Over a period of at least two years we will collect information about participants’ progress, any medical problems and their adherence to the randomised treatment allocation (start or avoid antiplatelet medication). This follow up information will be obtained from participants, relatives and General Practitioners.

What are the possible benefits and risks of participating?
We do not know whether taking or avoiding antiplatelet medication is best, but participants have a chance to be exposed to the benefit of one or other strategy by participating. Some people find it beneficial to be part of a research study and to be under regular follow-up. The results of this study will help us to treat patients better in future. Participants may find the time spent completing one questionnaire each year inconvenient. Participants, who have agreed to have an MRI scan, may become claustrophobic in the MRI scanner - if this happens the scan would be stopped. Because MRI scans are so detailed, there is also a 1 in 37 chance of finding an abnormality on your MRI scan that is completely incidental to your brain haemorrhage.

Where is the study run from and how long will it last?
RESTART is run by a team at the Division of Clinical Neurosciences at the University of Edinburgh, UK and it will last for at least five years.

When is the study starting and how long is it expected to run for?
It is anticipated that recruitment will begin in April 2013. Recruitment of participants to the trial will last for at least two years. Follow-up of these participants will continue for at least two years.

Who is funding the study?
RESTART is funded by the British Heart Foundation

Who is the main contact?
The UK Chief Investigator is Rustam Al-Shahi Salman and the Trial Manager is Karen Innes, and they can be contacted via RESTART.trial@ed.ac.uk.

Trial website

http://www.restarttrial.org

Contact information

Type

Scientific

Primary contact

Mrs Karen Innes

ORCID ID

Contact details

Bramwell Dott Building
Department of Clinical Neurosciences
Crewe Road South
Edinburgh
EH4 2XU
United Kingdom
-
karen.innes@ed.ac.uk

Additional identifiers

EudraCT number

2012-003190-26

ClinicalTrials.gov number

Protocol/serial number

14297

Study information

Scientific title

REstart or STop Antithrombotics Randomised Trial

Acronym

RESTART

Study hypothesis

For adults surviving spontaneous (non-traumatic) intracerebral haemorrhage (ICH) who had taken an antithrombotic (i.e. anticoagulant or antiplatelet) drug for the prevention of vaso-occlusive disease before the ICH, does a policy of starting antiplatelet drugs result in a beneficial net reduction of all serious vascular events over at least two years compared with a policy of avoiding antiplatelet drugs?

More details can be found at: http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=14297

Ethics approval

Scotland A Research Ethics Committee, 02/11/2012, ref: 12/SS/0138

Study design

Interventional multicentre parallel group prospective randomised open blinded end-point (PROBE) clinical trial, Design type: Treatment

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Intracerebral haemorrhage

Intervention

1. Patients will be randomised to either 'start antiplatelet medication' (restricted to the use of one or more of aspirin, dipyridamole or clopidogrel at the investigator's discretion) or 'avoid antiplatelet medication'.
2. Additional pre-randomisation brain MRI (for patients participating in the MRI sub-study)

Intervention type

Drug

Phase

Not Applicable

Drug names

Aspirin, dipyridamole, clopidogrel

Primary outcome measures

1. Recurrent symptomatic ICH
2. Fatal or non-fatal radiographically- or pathologically-proven recurrent symptomatic

Measured over 2 years after baseline, detected using annual general practitioner and participant follow-up, with independent, blinded adjudication of the clinical information and investigations relating to every reported outcome

Secondary outcome measures

1. Possible recurrent ICH
2. Symptomatic non-fatal extracerebral haemorrhage, extracranial haemorrhage, and vaso-occlusive events
3. Death
4. Modified Rankin Scale score
5. Adherence to antiplatelet drug(s)

1. Fatal events (i.e. followed by death within 30 days): complication of qualifying ICH; symptomatic extradural/subdural/subarachnoid/intraventricular haemorrhage; symptomatic major extracranial haemorrhage; symptomatic vaso-occlusive events; cardiac death with symptoms suggestive of myocardial ischaemia (type 3) or evidence of arrhythmia; deaths from any other known cause; rapidly fatal stroke, consistent with the clinical manifestations of ICH, but without radiographic or pathological confirmation; unwitnessed deaths without a clear cause and without further investigation.
2. Non-fatal events (i.e. not followed by death within 30 days): symptomatic extradural/subdural/subarachnoid/intraventricular haemorrhage; symptomatic major extracranial haemorrhage; symptomatic vaso-occlusive events; non-fatal stroke, with brain imaging performed too late to distinguish ICH from cerebral infarction.
Timepoint: over 2 years after baseline, detected using annual general practitioner and participant follow-up, with independent, blinded adjudication of the clinical information and investigations relating to every reported outcome

Annual ratings of participant function:
Simplified modified Rankin Scale postal questionnaire or Structured telephone interview with non-responders to the postal questionnaire, completed by the participant or their carer.

Overall trial start date

01/04/2013

Overall trial end date

01/04/2015

Reason abandoned

Eligibility

Participant inclusion criteria

1. Patient age 18 years or over, either sex
2. Spontaneous intracerebral haemorrhage (ICH) not attributable to preceding traumatic brain injury, on the basis of:
2.1. A history from the patient/witness of spontaneous symptom onset without preceding head trauma (head trauma occurring subsequent to ICH symptom onset is permissible)
2.2. brain imaging appearances consistent with spontaneous ICH (which may be accompanied by the brain/bone/soft tissue appearances of trauma occurring subsequently)
2.3. Either 'secondary' to an underlying structural cause (e.g. aneurysm, tumour, arteriovenous malformation, or intracranial venous thrombosis), or 'primary' (if the investigator either does not suspect an underlying structural cause, or it is not detected by further radiographic investigation)
3. Patient had taken an antithrombotic (i.e. anticoagulant or antiplatelet) drug for the prevention of vaso-occlusive disease for any length of time before the onset of the qualifying ICH.
4. Patient is at least 24 hours after ICH symptom onset (randomisation is expected to usually occur when they are approaching the end of their hospital admission/assessment for the qualifying ICH).
5. Patient and their doctor are both uncertain about whether to start or avoid antiplatelet drugs.
6. Patient is registered with a general practitioner (GP).
7. Brain imaging study that first diagnosed the qualifying ICH is available.
8. Consent to randomisation from the patient (or personal / legal / professional representative if the patient does not have mental capacity).
9. If eligible for the brain MRI sub-study, the MRI must be performed after the ICH but before randomisation.

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 720; UK Sample Size: 720

Participant exclusion criteria

1. ICH due to traumatic brain injury, in the opinion of the investigator
2. ICH due to haemorrhagic transformation of an ischaemic stroke, in the opinion of the investigator
3. Patient is taking an anticoagulant drug following ICH
4. Patient is pregnant, breastfeeding, or of childbearing age and not taking contraception
5. Patient is being treated or followed up in another Clinical Trial of an Investigational Medicinal Product (CTIMP)
6. Patient and carer unable to understand spoken or written English (local translator is not available)
7. Patients are ineligible for the brain MRI sub-study if they are claustrophobic or they have a contraindication to MRI

Recruitment start date

01/04/2013

Recruitment end date

31/01/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Bramwell Dott Building
Edinburgh
EH4 2XU
United Kingdom

Sponsor information

Organisation

University of Edinburgh (UK)

Sponsor details

Medical Statistics Unit
Department of Public Health Sciences
Teviot Place
Edinburgh
EH8 9AG
United Kingdom

Sponsor type

University/education

Website

http://www.ed.ac.uk

Funders

Funder type

Charity

Funder name

British Heart Foundation (BHF) (UK)

Alternative name(s)

BHF

Funding Body Type

private sector organisation

Funding Body Subtype

foundation

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes