Condition category
Circulatory System
Date applied
02/10/2017
Date assigned
09/10/2017
Last edited
18/11/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Current plain English summary as of 14/02/2020:
Background and study aims
About 35,000 people each year in the UK have a type of stroke, called ‘lacunar’ or ‘small vessel’ stroke, which is different to other common types of stroke and for which there is no proven treatment. Small vessel stroke may be caused by damage to the lining of the tiny blood vessels deep inside the brain that stops them functioning normally. This not only causes stroke but, perhaps more importantly, causes problems with thinking and walking, possibly causing up to 45% of all dementias either on its own, or mixed with Alzheimer’s disease (about 350,000 patients in the UK). Some drugs that are commonly used in other blood vessel diseases may help improve small vessel function and prevent worsening of brain damage. One drug (cilostazol) has been tested in patients with stroke in the Asia Pacific countries but not on dementia; the other drug (isosorbide mononitrate) is widely used in the UK for heart disease but not stroke. The aim of this study is to test if the study methods are practical so that patients and trial centres can follow the procedures, and to confirm how many patients have more stroke-like symptoms or experience worsening of their thinking skills. This information is needed to be sure that a very large clinical trial to find out if these drugs can prevent worsening of small vessel disease will be possible.

Who can participate?
Adults aged 30 and older who have had a small vessel stroke.

What does the study involve?
Participants are randomly allocated to one of four groups. Those in the first group receive cilostazol by mouth twice a day. Those in the second group receive the isosorbide mononitrate by mouth 20 mg twice a day or 50 mg once a day if the extended release formulation used. Those in the third group receive both medications in the same doses and ways above. Those in the last group do not receive any treatment. The treatment lasts one year. Participants are followed up around one to two weeks and three to four weeks by phone as well as six and 12 months by a phone or face to face meeting to assess the tolerability and safety of the medication. The last follow up visit includes a brain scan.

What are the possible benefits and risks of participating?
There are no direct benefits with participation, although some patients find the regular check-ups reassuring and the MRI Brain scan may give more details to your doctors about their stroke. There are no foreseeable risks however there is a chance that you may experience side effects from the Trial drugs. Both drugs have been used for many years to treat other conditions so the side effects are well known. If any of these occur, they are usually noticed when first starting the tablets.

Where is the study run from?
1. Royal Infirmary of Edinburgh (UK)
2. Nottingham City Hospital (UK)
3. NHS Fife, Victoria Hospital (UK)
4. Queen Elizabeth University Hospital Glasgow (UK)
5. Bradford Royal Infirmary (UK)
6. Aberdeen Royal Infirmary (UK)
7. Leeds General Infirmary (UK)
8. Royal Derby Hospital Centre (UK)
9. Raigmore Hospital Inverness (UK)
10. St George's Hospital London (UK)
11. King's College Hospital London (UK)
12. Broomfield Hospital Essex (UK)
13. University Hospital of North Tees (UK)
14. Royal Hallamshire Hospital (UK)
15. Sandwell General Hospital (UK)
16. Royal Hampshire County Hospital (UK)
17. University College London (UK)
18. Northwick Park Hospital (UK)
19. Luton and Dunstable NHSFT University Hospital (UK)
20. Doncaster Royal Infirmary (UK)
21. New Cross Hospital Wolverhampton (UK)
22. Calderdale Royal Hospital (UK)
23. Musgrove Park Hospital (UK)
24. Southampton General Hospital (UK)
25. Homerton University Hospital (UK)
26. Royal Devon and Exeter Hospital (UK)

When is the study starting and how long is it expected to run for?
May 2017 to August 2022 (updated 18/11/2020, previously: December 2022)

Who is funding the study?
British Heart Foundation (BHF) (UK)

Who is the main contact?
1. LACI-2 Trial Manager
laci-2@ed.ac.uk
2. Professor Joanna Wardlaw
Joanna.Wardlaw@ed.ac.uk
(updated 18/11/2020, previously: Dr Anna Heye
anna.heye@ed.ac.uk)


Previous plain English summary as of 11/09/2019:
Background and study aims
About 35,000 people each year in the UK have a type of stroke, called ‘lacunar’ or ‘small vessel’ stroke, which is different to other common types of stroke and for which there is no proven treatment. Small vessel stroke may be caused by damage to the lining of the tiny blood vessels deep inside the brain that stops them functioning normally. This not only causes stroke but, perhaps more importantly, causes problems with thinking and walking, possibly causing up to 45% of all dementias either on its own, or mixed with Alzheimer’s disease (about 350,000 patients in the UK). Some drugs that are commonly used in other blood vessel diseases may help improve small vessel function and prevent worsening of brain damage. One drug (cilostazol) has been tested in patients with stroke in the Asia Pacific countries but not on dementia; the other drug (isosorbide mononitrate) is widely used in the UK for heart disease but not stroke. The aim of this study is to test if the study methods are practical so that patients and trial centres can follow the procedures, and to confirm how many patients have more stroke-like symptoms or experience worsening of their thinking skills. This information is needed to be sure that a very large clinical trial to find out if these drugs can prevent worsening of small vessel disease will be possible.

Who can participate?
Adults aged 30 and older who have had a small vessel stroke.

What does the study involve?
Participants are randomly allocated to one of four groups. Those in the first group receive cilostazol by mouth twice a day. Those in the second group receive the isosorbide mononitrate by mouth 20 mg twice a day or 50 mg once a day if the extended release formulation used. Those in the third group receive both medications in the same doses and ways above. Those in the last group do not receive any treatment. The treatment lasts one year. Participants are followed up around one to two weeks and three to four weeks by phone as well as six and 12 months by a phone or face to face meeting to assess the tolerability and safety of the medication. The last follow up visit includes a brain scan.

What are the possible benefits and risks of participating?
There are no direct benefits with participation, although some patients find the regular check-ups reassuring and the MRI Brain scan may give more details to your doctors about their stroke. There are no foreseeable risks however there is a chance that you may experience side effects from the Trial drugs. Both drugs have been used for many years to treat other conditions so the side effects are well known. If any of these occur, they are usually noticed when first starting the tablets.

Where is the study run from?
1. Royal Infirmary of Edinburgh (UK)
2. Nottingham City Hospital (UK)

When is the study starting and how long is it expected to run for?
May 2017 to November 2020

Who is funding the study?
British Heart Foundation (BHF) (UK)

Who is the main contact?
1. Dr Anna Heye
anna.heye@ed.ac.uk
2. Professor Joanna Wardlaw
Joanna.Wardlaw@ed.ac.uk


Previous plain English summary:
Background and study aims
About 35,000 people each year in the UK have a type of stroke, called ‘lacunar’ or ‘small vessel’ stroke, which is different to other common types of stroke and for which there is no proven treatment. Small vessel stroke may be caused by damage to the lining of the tiny blood vessels deep inside the brain that stops them functioning normally. This not only causes stroke but, perhaps more importantly, causes problems with thinking and walking, possibly causing up to 45% of all dementias either on its own, or mixed with Alzheimer’s disease (about 350,000 patients in the UK). Some drugs that are commonly used in other blood vessel diseases may help improve small vessel function and prevent worsening of brain damage. One drug (cilostazol) has been tested in patients with stroke in the Asia Pacific countries but not on dementia; the other drug (isosorbide mononitrate) is widely used in the UK for heart disease but not stroke. The aim of this study is to test if the study methods are practical so that patients and trial centres can follow the procedures, and to confirm how many patients have more stroke-like symptoms or experience worsening of their thinking skills. This information is needed to be sure that a very large clinical trial to find out if these drugs can prevent worsening of small vessel disease will be possible.

Who can participate?
Adults aged 30 and older who have had a small vessel stroke.

What does the study involve?
Participants are randomly allocated to one of four groups. Those in the first group receive cilostazol by mouth twice a day. Those in the second group receive the isosorbide mononitrate by mouth 20 mg twice a day or 50 mg once a day if the extended release formulation used. Those in the third group receive both medications in the same doses and ways above. Those in the last group do not receive any treatment. The treatment lasts one year. Participants are followed up around one to two weeks and three to four weeks by phone as well as six and 12 months by a phone or face to face meeting to assess the tolerability and safety of the medication. The last follow up visit includes a brain scan.

What are the possible benefits and risks of participating?
There are no direct benefits with participation, although some patients find the regular check-ups reassuring and the MRI Brain scan may give more details to your doctors about their stroke. There are no foreseeable risks however there is a chance that you may experience side effects from the Trial drugs. Both drugs have been used for many years to treat other conditions so the side effects are well known. If any of these occur, they are usually noticed when first starting the tablets.

Where is the study run from?
1. Royal Infirmary of Edinburgh (UK)
2. Nottingham City Hospital (UK)

When is the study starting and how long is it expected to run for?
May 2017 to November 2020

Who is funding the study?
British Heart Foundation (BHF) (UK)

Who is the main contact?
1. Dr Julia Boyd
julia.boyd@ed.ac.uk
2. Professor Joanna Wardlaw
Joanna.Wardlaw@ed.ac.uk

Trial website

https://stroke.nottingham.ac.uk/laci-2/

Contact information

Type

Public

Primary contact

Dr LACI-2 Trial Manager

ORCID ID

Contact details

Edinburgh Clinical Trials Unit
University of Edinburgh (Usher Institute)
NINE
9 Little France Road
Edinburgh BioQuarter
Edinburgh
EH16 4UX
United Kingdom
+44 131 651 9901
laci-2@ed.ac.uk

Type

Scientific

Additional contact

Prof Joanna Wardlaw

ORCID ID

http://orcid.org/0000-0002-9812-6642

Contact details

Neuroimaging Sciences
University of Edinburgh
Centre for Clinical Brain Sciences (CCBS)
Chancellor's Building
49 Little France Crescent
Edinburgh
EH16 4SB
United Kingdom
+44 131 465 9599
Joanna.Wardlaw@ed.ac.uk

Additional identifiers

EudraCT number

2016-002277-35

ClinicalTrials.gov number

NCT03451591

Protocol/serial number

36168

Study information

Scientific title

LACunar Intervention (LACI-2) Trial-2: Assessment of safety and efficacy of cilostazol and isosorbide mononitrate to prevent recurrent lacunar stroke and progression of cerebral small vessel disease

Acronym

LACI-2

Study hypothesis

The trial hypothesis is to test whether a much larger scale study testing the effects of Cilostazol and ISMN on preventing brain damage from small vessel disease will be feasible. We will assess how easy is it to identify suitable patients, how many of them are willing to take part in the study and how many stay on the study for the full 12 months. Feedback from participants on study procedures/burden will also inform any future studies. We will also collect information on how many patients have another stroke, experience difficulties in independent daily living or in thinking skills, and on drug safety such as bleeding.

Ethics approval

East Midlands - Nottingham 2 REC, 10/05/2017, ref: 17/EM/0077 00:00:00

Study design

Randomised; Interventional; Design type: Treatment, Drug

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

Prevention of stroke

Intervention

Randomisation involves minimisation on a number of key prognostic factors. An electronic randomisation system is used to allocate participants to one of four groups as detailed below. All patients receive best medical therapy for stroke prevention in addition to their randomly allocated trial treatment. Trial treatment period is 54 weeks.
1. Cilostazol: oral, 100mg twice a day
2. Isosorbide mononitrate (ISMN): oral, 20mgs twice a day or 50mg once a day if extended release formulation used
3. Cilostazol + ISMN - same doses as above
4. No trial treatment

There are 4 follow-up time points:
1. One-two week follow-up by phone
2. Three-four week follow-up by phone
3. Six month follow-up by phone or face to face
4. 12 month follow-up by phone or face to face

At the end of the 12 months they will stop their allocated treatment, have their final visit which includes a brain scan.

Intervention type

Drug

Phase

Phase II

Drug names

cilostazol, Isosorbide mononitrate

Primary outcome measure

Feasibility of a future Phase III trial is the primary outcome and is measured at 36 months. This will be attained if the feasibility target sample size of 400 patients are recruited in 24 months in the UK and >95% retained in follow-up at one year.

Secondary outcome measures

1. Assessment of drug tolerability are measured using questionnaires and reviewing patient notes at one-two weeks, three-four weeks, six months and 12 months
2. Safety is measured using questionnaires and reviewing patient notes at one-two weeks, three-four weeks, six months and 12 months
3. Event is measured using questionnaires and reviewing patient notes at one-two weeks, three-four weeks, six months and 12 months
4. Recruitment rates are measured using questionnaires and reviewing patient notes at one-two weeks, three-four weeks, six months and 12 months. Questionnaires include a study specific structured questionnaire to record symptoms, medication history and IMP adherence and a vascular event questionnaire.

Overall trial start date

01/11/2017

Overall trial end date

31/08/2022

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Clinical lacunar stroke syndrome.
2. Brain scanning* with MR including diffusion imaging wherever possible, and obtained soon after the presentation with stroke, shows either:
2.1. A recent, relevant (in time and location) acute lacunar infarct on diffusion MR imaging1,
2.2. Or, if no visible acute lacunar infarct on diffusion MR imaging2 then there is no competing pathology as a cause for stroke (e.g. no acute cortical infarct, no acute intra-cerebral haemorrhage, no stroke mimic such as tumour, subdural haematoma);
2.3. If only a CT brain scan is available as in section 3 above, then there is a small relevant (in age and location) subcortical infarct, or if no infarct then there is no competing pathology as a cause for stroke (e.g. no acute cortical infarct, no acute intra-cerebral haemorrhage, no stroke mimic such as tumour, subdural haematoma). Note that if there is no acute lacunar infarct on MR diffusion imaging but there is a recent-appearing lacunar infarct on FLAIR, T2, or T1 (i.e. no cavitation or ex-vacuo effect; may be slightly swollen, ill-defined edges; or scan in the few weeks before the stroke does not show a lesion but there is an acute lacunar infarct on MR T2, FLAIR, T1 scanning after the stroke in an appropriate area of the brain for symptoms), then the T2, FLAIR, T1 lesion may be counted as the acute lacunar infarct in the absence of a diffusion lesion. Similarly, on CT2 a recent relevant small subcortical infarct would not show cavitation or shrinkage/ex vacuo effect. Note that about a third of patients with a clinically definite lacunar syndrome do not have a corresponding recent infarct visible on MRI but should still be classed as ‘lacunar stroke’ if no other explanation can be found for the symptoms. The presence of a recent cortical infarct on FLAIR, T2, T1, the recent timing being indicated by the characteristics above, would count as a competing pathology. Note that the complete absence of any abnormality on MR or CT brain imaging (no acute subcortical infarct or pre-existing SVD such as white matter hyperintensities, lacunes, etc.) while occasionally seen in lacunar stroke is unusual and should question the diagnosis of lacunar ischaemic stroke.
3. Age > 30 years
4. Independent in activities of daily living (modified Rankin ≤2)
5. Capacity to give consent themselves

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 400; UK Sample Size: 400

Participant exclusion criteria

1. Other significant active neurological illness present since suffering stroke (e.g. recurrent seizures, multiple sclerosis, brain tumour). Well-controlled epilepsy present prior to the stroke, a single seizure at onset of the stroke or provoked seizure is not an exclusion.
2. Requiring assistance with activities of daily living (Modified Rankin ≥3)
3. Has been diagnosed as having dementia on formal clinical assessment
4. Active cardiac disease (atrial fibrillation, myocardial infarction in past 6 months, active angina, symptomatic cardiac failure)
5. Diagnosis of hypotension, defined as sitting systolic blood pressure less than 100mmHg
6. Definite indication for (i.e. already prescribed) either trial medication, or definite contraindication to a trial drug as per SmPCSPCs - lactose intolerance is a contraindication to ISMN preparations which contain lactose monohydrate - (indication for or contraindication to one of the trial drugs still allows randomisation to the other trial drug)
7. Unable to swallow tablets
8. Bleeding tendency (e.g. known platelets<100, active peptic ulcer, history of intracranial haemorrhage such as subdural haematoma, subarachnoid haemorrhage, intracerebral haemorrhage, but not asymptomatic haemorrhagic transformation of infarction or a few microbleeds, taking anticoagulant medication)
9. Unlikely to comply with trial medication based on knowledge of past history, lifestyle
10. Planned surgery during the trial period including carotid endarterectomy. Note prior and apparently successful carotid endarterectomy (or other surgery) is not an exclusion criterion and patients who would otherwise be eligible but require endarterectomy first may be randomised after recovery from successful endarterectomy.
11. Other concurrent life threatening illness
12. Unlikely to be available for follow-up (eg moving outside or visitor to the area)
13. History of drug overdose or attempted suicide or significant active mental illness
14. Pregnant or breastfeeding women, women of childbearing age not taking contraception. Acceptable contraception in women of childbearing age is a “highly effective” contraceptive measure as defined by the Clinical Trials Facilitation Group (http://www.hma.eu/fileadmin/dateien/Human_Medicines/01-About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf) and includes combined (oestrogen and progesterone containing) or progesterone-only contraception associated with inhibition of ovulation, or intrauterine device or bilateral tubal occlusion. Contraception must be continued for up to 30 days after the end of the IMP dosing
schedule.
15. Prohibited medications to either trial drug (see sections 4.5 of the appended SmPCSPCs and protocol section 6.6.3, plus no anticoagulant drugs); (prohibited medications to one of the trial drugs still allows randomisation to the other trial drug)
16. Renal impairment (creatinine clearance <25 ml/min)
17. Hepatic impairment
18. Current enrolment in another Clinical Trial of Investigational Medicinal Product (CTIMP); still in extended follow-up beyond the CTIMP primary outcome and no longer taking that trial’s IMP is not an exclusion to enrolment in LACI-2
19. Unable to tolerate MRI or contraindication to MRI (Claustrophobia, Pacemaker)

Recruitment start date

08/01/2018

Recruitment end date

31/05/2021

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Royal Infirmary of Edinburgh (Lead centre)
Royal Infirmary of Edinburgh 51 Little France Drive
Edinburgh
EH16 4SA
United Kingdom

Trial participating centre

Nottingham City Hospital
Hucknall Road
Nottingham
NG5 1PB
United Kingdom

Trial participating centre

NHS Fife, Victoria Hospital
Hayfield Road
Kirkcaldy
KY2 5AH
United Kingdom

Trial participating centre

Queen Elizabeth University Hospital Glasgow
1345 Govan Rd
Glasgow
G51 4TF
United Kingdom

Trial participating centre

Bradford Royal Infirmary
Duckworth Lane
Bradford
BD9 6RJ
United Kingdom

Trial participating centre

Aberdeen Royal Infirmary
Foresterhill
Aberdeen
AB25 2ZN
United Kingdom

Trial participating centre

Leeds General Infirmary
Martin Wing Great George Street
Leeds
LS1 3EX
United Kingdom

Trial participating centre

Royal Derby Hospital Centre
Uttoxeter Road
Derby
DE22 3DT
United Kingdom

Trial participating centre

Raigmore Hospital Inverness
Old Perth Road
Inverness
IV2 3UJ
United Kingdom

Trial participating centre

St George's Hospital
Blackshaw Road
London
SW17 0QT
United Kingdom

Trial participating centre

King's College Hospital London
Denmark Hill
London
SE5 9RS
United Kingdom

Trial participating centre

Broomfield Hospital Essex
Court Road
Chelmsford
CM1 7ET
United Kingdom

Trial participating centre

University Hospital of North Tees
Stroke Unit Ward 41
Stockton on Tees
TS19 8PE
United Kingdom

Trial participating centre

Royal Hallamshire Hospital
Glossop Road
Sheffield
S10 2JF
United Kingdom

Trial participating centre

Sandwell General Hospital
Lyndon
West Bromwich
B71 4HJ
United Kingdom

Trial participating centre

Royal Hampshire County Hospital
Romsey Road
Winchester
SO22 5DG
United Kingdom

Trial participating centre

University College London
London
WC1N 3BG
United Kingdom

Trial participating centre

Northwick Park Hospital
Watford Road
Harrow
HA1 3UJ
United Kingdom

Trial participating centre

Luton and Dunstable NHSFT University Hospital
Lewsey Road
Luton
LU4 0DZ
United Kingdom

Trial participating centre

Doncaster Royal Infirmary
Doncaster
DN2 5LT
United Kingdom

Trial participating centre

New Cross Hospital Wolverhampton
Wolverhampton Road
Wolverhampton
WV10 0QP
United Kingdom

Trial participating centre

Calderdale Royal Hospital
Salterhebble
Halifax
HX3 0PW
United Kingdom

Trial participating centre

Musgrove Park Hospital
Taunton
TA1 5DA
United Kingdom

Trial participating centre

Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom

Trial participating centre

Homerton University Hospital
Homerton Row
London
E9 6SR
United Kingdom

Trial participating centre

Royal Devon and Exeter Hospital
Barrack Road
Exeter
EX2 5DW
United Kingdom

Sponsor information

Organisation

University of Edinburgh and NHS Lothian - co-sponsors (UK)

Sponsor details

ACCORD Office
The Queen's Medical Research Institute
47 Little France Crescent
Edinburgh
EH16 4TJ
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

British Heart Foundation (BHF)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Current publication and dissemination plan as of 14/02/2020:
We are going to publish the study protocol in a peer-reviewed journal before the end of recruitment.

A Statistical Analysis Plan will be published prior to database lock and will describe analysis procedures and procedures for missing, unused or spurious data, and definitions of populations analyzed.

On completion of the study, a clinical study report will be prepared for publication in a peer-reviewed journal in accordance with ICH guidelines. A report will also be submitted to the funder (British Heart Foundation). Papers describing secondary analysis will also be published.

The clinical study report will be used for publication and presentation at scientific meetings on stroke and dementia such as UK Stroke Forum, European Stroke Organisation Conference, International Stroke Conference, the World Stroke Congress, and conferences on Alzheimer’s disease and dementia. Investigators have the right to publish orally or in writing the results of the study. Reporting will be in compliance with CONSORT.

Summaries of results will also be made available to all Investigators for dissemination within their clinics (where appropriate and according to their discretion).

A newsletter will be sent to the participants informing them of the results and of other information relevant to small vessel disease and general information about maintaining a healthy lifestyle.

IPD sharing statement:
The datasets generated during and/or analyzed during the current study are/will be available upon request from Dr Anna Heye (anna.heye@ed.ac.uk) or Professor Joanna Wardlaw (Joanna.Wardlaw@ed.ac.uk).


Previous publication and dissemination plan:
On completion of the study a clinical study report will be prepared for publication in a peer reviewed journal in accordance with ICH guidelines. A report will also be submitted to the funder (British Heart Foundation). Papers describing secondary analysis will also be published.
The clinical study report will be used for publication and presentation at scientific meetings on stroke and dementia such as UK Stroke Forum, European Stroke Organisation Conference, International Stroke Conference, the World Stroke Congress, and conferences on Alzheimer’s disease and dementia. Investigators have the right to publish orally or in writing the results of the study. Reporting will be in compliance with CONSORT.
Summaries of results will also be made available to all Investigators for dissemination within their clinics (where appropriate and according to their discretion).
A newsletter will be sent to the participants informing them of the results and of other information relevant to small vessel disease and general information about maintaining a healthy lifestyle.

IPD sharing statement:
The datasets generated during and/or analysed during the current study are/will be available upon request from Dr Julia Boyd julia.boyd@ed.ac.uk or Professor Joanna Wardlaw Joanna.Wardlaw@ed.ac.uk

Intention to publish date

31/08/2023

Participant level data

Available on request

Basic results (scientific)

Publication list

2020 protocol in https://pubmed.ncbi.nlm.nih.gov/33072884/ (added 20/10/2020)

Publication citations

Additional files

Editorial Notes

18/11/2020: The following changes were made to the trial record: 1. The recruitment resumed. 2. The trial website was added. 3. The ClinicalTrials.gov number was added. 4. The overall end date was changed from 28/02/2022 to 31/08/2022. 5. The recruitment end date was changed from 30/11/2020 to 31/05/2021. 6. The intention to publish date was changed from 01/11/2022 to 31/08/2023. 7. The primary contact details were changed. 20/10/2020: Publication reference added. 23/04/2020: Due to current public health guidance, recruitment for this study has been paused. 14/02/2020: The following changes have been made: 1. The publication and dissemination plan has been updated. 2. The trial participating centres "NHS Fife, Victoria Hospital", "Queen Elizabeth University Hospital Glasgow", "Bradford Royal Infirmary", "Aberdeen Royal Infirmary", "Leeds General Infirmary", "Royal Derby Hospital Centre", "Raigmore Hospital Inverness", "St George's Hospital London", "King's College Hospital London", "Broomfield Hospital Essex", "University Hospital of North Tees", "Royal Hallamshire Hospital", "Sandwell General Hospital", "Royal Hampshire County Hospital", "University College London", "Northwick Park Hospital", "Luton and Dunstable NHSFT University Hospital", "Doncaster Royal Infirmary", "New Cross Hospital Wolverhampton", "Calderdale Royal Hospital", "Musgrove Park Hospital", "Southampton General Hospital", "Homerton University Hospital", and "Royal Devon and Exeter Hospital" have been added. 3. The plain English summary has been updated to reflect the changes above and those made on 21/01/2020. 21/01/2020: The following changes have been made: 1. The condition has been changed from "Specialty: Stroke, Primary sub-specialty: Rehabilitation; UKCRC code/ Disease: Stroke/ Cerebrovascular diseases" to "Prevention of stroke" following a request from the NIHR. 2. The condition category has been changed from "Nervous System Diseases" to "Circulatory System". 06/12/2019: The following changes have been made: 1. The recruitment end date has been changed from 30/11/2019 to 30/11/2020. 2. The overall trial end date has been changed from 28/02/2021 to 28/02/2022. 3. The intention to publish date has been changed from 01/11/2021 to 01/11/2022. 11/09/2019: The following changes were made: 1. The recruitment start date was changed from 01/06/2017 to 08/01/2018. 2. The recruitment end date was changed from 31/08/2017 to 30/11/2019. 3. The overall trial start date was changed from 01/05/2017 to 01/11/2017. 4. The overall trial end date was changed from 31/12/2017 to 28/02/2021. 5. The public contact was updated. 6. The plain English summary was updated. 19/02/2019: The following changes were made: 1. The overall end date was changed from 01/11/2020 to 31/12/2017 2. The recruitment start date was changed from 01/11/2017 to 01/06/2017 3. The recruitment end date was changed from 01/11/2019 to 31/08/2017