Condition category
Circulatory System
Date applied
06/02/2020
Date assigned
20/04/2020
Last edited
29/04/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Strokes are very common with ~100 000 strokes occurring every year in the UK. The majority (80%) are caused by a blocked blood vessel and others are caused by a ruptured blood vessel. There are very few treatments for strokes, such as using medicines or wires to unblock blood vessels, but they can only be used in a small proportion of strokes caused by blocked blood vessels.
A treatment called ‘remote ischaemic conditioning’ (RIC) could help protect the brain from damage caused by stroke. RIC is performed by inflating a blood pressure cuff on the arm, which briefly interrupts its blood supply; the cuff is deflated after 5 minutes and the cycle is repeated 4 times. The process causes body chemicals to be released into the blood stream which have a protective effect on the brain and may reduce the size of the stroke and reduce disability – this has been shown in experimental models of stroke but the treatment has not been proven in humans.

We have completed a small trial of 26 stroke patients (called RECAST-1) which used RIC soon after their stroke - RIC was very well tolerated and caused minimal side-effects. We have also completed a second trial (RECAST-2) of 60 stroke patients showing we can perform RIC urgently within 6 hours of new stroke symptoms. The trial has also suggested that RIC may be able to prevent ongoing damage caused by stroke.

We plan to perform a trial across 60 UK hospitals including 1300 stroke patients called RECAST-3. Half of the participants will receive RIC, and the other half will have a dummy procedure performed (a placebo). Patients will be identified and invited to take part in the trial by the Stroke Team as soon as they arrive in hospital. The participants will have a 50:50 chance of receiving RIC or the placebo procedure. RIC or placebo is performed twice on the first day and twice on day two. Consent can be given by a relative or carer if the patient is not able to give it themselves. This will occur at the same time as routine treatments (such as receiving clot-busting medicine). The participant will be invited to take part in other parts to the study, including additional brain scans looking at the size of the stroke and blood tests (measuring blood proteins). The participant will be seen again by the research team on the 4th day after admission to answer questions on the trial treatment. After discharge from hospital, the participant will be contacted over the telephone 3 months later to answer questions about their physical ability, mood, memory and quality of life.

It is likely that new treatments will have their greatest effect if administered in the first few hours after a stroke. RIC is an attractive potential treatment since it would be simple and cheap to administer by medics, other healthcare professionals (nurses, paramedics) or even non-medically trained personnel. If this study shows that RIC is beneficial in reducing stroke recurrence and leading to a lower level of disability, it would have significant social, medical and financial benefit to patients, families and society.

Who can participate?
Patients at one of the participating hospitals who have a diagnosis of an ischaemic (blocked blood vessel) stroke. Patients who are over 18 years old and within 6 h of their stroke starting will be included.

What does the study involve?
Patients who have been diagnosed with a stroke will be recruited to the study in hospital.

Participants will either receive a treatment called ‘remote ischaemic conditioning’ (RIC) or a placebo treatment. RIC is performed by inflating a blood pressure cuff on the arm, which briefly interrupts its blood supply; the cuff is deflated after 5 minutes and the cycle is repeated 4 times. Participants will receive this treatment 4 times within 54 hours of the onset of their stroke.

Participants will be assessed by doctors while in hospital and will have a follow-up assessment by telephone call after 90 days.

What are the possible benefits and risks of participating?
We cannot promise the study will help participants but it might help reduce how badly the current stroke affects participants or it might reduce the chances of having another stroke. The information we get from this study will help in deciding the best treatments for future stroke patients.

The main disadvantage is that participants may experience some discomfort when the blood pressure cuff is kept inflated. There is a small risk that prolonged cuff inflation could cause bruising or bleeding under the skin of the participant's arm and this will be monitored closely.

Participants in the study will have a second CT brain scan on day 2. This might already be arranged as part of their standard care depending on the treatment already received. This procedure uses ionising radiation to form images of the head and provide the doctor with clinical information. Ionising radiation can cause cell damage that may, after many years or decades, turn cancerous. We are all at risk of developing cancer during our lifetime. The normal risk is that this will happen to about 50% of people at some point in their life. Taking part in this study will increase the chances of this happening to participants from 50% to 50.02%

Where is the study run from?
The study is run from the University of Nottingham (UK) and will take place at 60 hospitals in the UK

When is the study starting and how long is it expected to run for?
From April 2020 to December 2023

Who is funding the study?
The National Institute for Health Research (UK)

Who is the main contact?
Mrs Diane Harvard
diane.havard@nottingham.ac.uk

Trial website

Contact information

Type

Public

Primary contact

Mrs Diane Havard

ORCID ID

http://orcid.org/0000-0002-3257-1137

Contact details

A07 Clinical Sciences Building
City Hospital Campus
Hucknall Road
Nottingham
NG5 1PB
United Kingdom
+44 0115 823 1775
diane.havard@nottingham.ac.uk

Type

Scientific

Additional contact

Dr Tim England

ORCID ID

http://orcid.org/0000-0001-5330-8584

Contact details

Vascular Medicine
Division of Medical Sciences & GEM
University of Nottingham
Royal Derby Hospital Centre
Derby
DE22 3DT
United Kingdom
+44 1332 724668
timothy.england@nottingham.ac.uk

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

20011, CPMS 44839, IRAS 282606

Study information

Scientific title

Remote Ischaemic Conditioning After Stroke Trial (ReCAST- 3)

Acronym

ReCAST-3

Study hypothesis

Remote ischaemic perconditioning (RIC) is safe and improves functional outcome in patients presenting with hyperacute stroke.

Ethics approval

Awaiting response, review date 09/04/2020, Greater Manchester (GM) South Health Research Authority (Barlow House, 4 Minshull St, Manchester, M1 3DZ UK; gmsouth.rec@hra.nhs.uk; +44 0207 104 8221 or +44 0207 104 8063)

Study design

Phase III prospective randomised (1:1) sham-controlled blinded-endpoint parallel-group multicentre trial.

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Quality of life

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Adults with hyperacute ischaemic stroke presenting in Emergency Departments and Stroke Units in the UK.

Intervention

Participants will be allocated to either receive the intervention or the comparator.

The intervention/remote ischaemic conditioning group will receive 4 cycles of intermittent limb ischaemia, alternating 5 mins inflation (+20 mmHg above systolic BP) followed by 5 mins deflation of an automated upper arm blood pressure cuff.

The comparator/sham remote ischaemic conditioning group will receive 4 cycles of an automated upper arm blood pressure cuff inflated to 20 mmHg for 5 mins followed by 5 mins deflation.

For both groups, the first dose will be given within < 6 h of onset, the second dose will be given 1-2 h after the first dose. This will be repeated twice daily until the end of day 2 for total 4 doses.

All participants will be followed up via telephone call at 90 days blinded to treatment allocation.

Intervention type

Device

Phase

Phase III

Drug names

N/A

Primary outcome measure

Death or dependency assessed by the modified Rankin Scale (mRS) ordinal shift analysis recorded using central blinded telephone follow-up at 90 days.

Secondary outcome measures

1. Adverse events including: death, neurological deterioration, intracranial haemorrhage, systemic embolism, and other serious adverse events measured through clinical assessment at 2 and 4 days, patient notes at discharge, and responses to central blinded telephone follow-up at 90 days
2. Cerebrovascular events measured through clinical assessment at 2 and 4 days, patient notes at discharge, and responses to central blinded telephone follow-up at 90 days
3. Major adverse cardiac and cerebral events measured through clinical assessment at 2 and 4 days, patient notes at discharge, and responses to central blinded telephone follow-up at 90 days
4. Acute kidney injury measured through clinical assessment at 2 and 4 days, patient notes at discharge, and responses to central blinded telephone follow-up at 90 days
5. Disability measured through responses to central blinded telephone follow-up at 90 days
6. Cognition measured through responses to central blinded telephone follow-up at 90 days
7. Mood measured through responses to central blinded telephone follow-up at 90 days
8. Frailty measured through responses to central blinded telephone follow-up at 90 days
9. Quality of life measured through responses to central blinded telephone follow-up at 90 days

Overall trial start date

01/04/2020

Overall trial end date

31/12/2023

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

Current inclusion criteria as of 29/04/2020:
1. Hyperacute ischaemic stroke
2. < 6 h post stroke onset
3. Primary intracerebral haemorrhage ruled out on baseline clinical neuroimaging
4. NIHSS score of greater than 3 at randomisation
5. Aged 18 years or above

Previous inclusion criteria:
1. Hyperacute ischaemic stroke
2. < 6 h post stroke onset
3. Primary intracerebral haemorrhage ruled out on baseline clinical neuroimaging
4. NIHSS score > 4 at randomisation
5. Aged > 18 years

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

1300

Participant exclusion criteria

Current exclusion criteria as of 29/04/2020:
1. Pre-morbid dependency (modified Rankin Scale, mRS> 3)
2. Spontaneous intracerebral haemorrhage
3. Dementia
4. Coma (GCS < 8)
5. Malignancy
6. Significant co-morbidity (life expectancy < 6 months)
7. BM < 3.0 mmol/L
8. Seizure on presentation unless brain imaging identifies evidence of significant brain ischaemia
9. Known pregnancy

Previous exclusion criteria:
1. Pre-morbid dependency (modified Rankin Scale, mRS> 3)
2. Spontaneous intracerebral haemorrhage
3. Dementia
4. Coma (GCS < 8)
5. Malignancy
6. Significant co-morbidity (life expectancy < 6 months)
7. BM < 3.0 mmol/L
8. Seizure on presentation unless brain imaging identifies evidence of significant brain ischaemia
9. Long term (> 7 days) nitrate therapy
10. Receiving treatment for diabetes
11. Pregnancy

Recruitment start date

01/07/2020

Recruitment end date

01/07/2023

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Royal Derby Hospital
Uttoxeter Road
Derby
DE22 3NE
United Kingdom

Trial participating centre

Leicester Royal Infirmary
Infirmary Square
Leicester
LE1 5WW
United Kingdom

Trial participating centre

University Hospital of Hartlepool
Holdforth Road
Hartlepool
TS24 9AH
United Kingdom

Trial participating centre

Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Trial participating centre

Yeovil District Hospital
Higher Kingston
Yeovil
BA21 4AT
United Kingdom

Trial participating centre

Arrowe Park Hospital
Arrowe Park Road
Upton Wirral
CH49 5PE
United Kingdom

Trial participating centre

Watford General Hospital
Vicarage Road
Watford
WD18 0HB
United Kingdom

Trial participating centre

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

Trial participating centre

Kent and Canterbury Hospital
Ethelbert Road
Canterbury
CT1 3NG
United Kingdom

Trial participating centre

Nottingham City Hospital
Hucknall Road
Nottingham
NG5 1PB
United Kingdom

Trial participating centre

Edith Cavell Hospital
Bretton Gate
Peterborough
PE3 9GZ
United Kingdom

Trial participating centre

Royal Preston Hospital
Sharoe Green Lane
Preston
NG5 1PB
United Kingdom

Trial participating centre

Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom

Trial participating centre

Southmead Hospital
Southmead Road
Bristol
BS10 5NB
United Kingdom

Trial participating centre

Ulster Hospital
Upper Newtownards Road
Dundonald
BT16 1RH
United Kingdom

Trial participating centre

Aberdeen Royal Infirmary
Fosterhill Road
Aberdeen
AB25 2ZN
United Kingdom

Trial participating centre

Royal United Hospital
Combe Park
Bath
BA1 3NG
United Kingdom

Trial participating centre

Queen Elizabeth Medical Centre
Mindelsohn Way
Birmingham
B15 2TH
United Kingdom

Trial participating centre

Countess of Chester Hospital
Liverpool Rd
Chester
CH2 1UL
United Kingdom

Trial participating centre

Doncaster Royal Infirmary
Armthorpe Road
Doncaster
DN2 5LT
United Kingdom

Trial participating centre

Gartnavel Royal Hospital
1055 Great Western Road
Glasgow
G12 0XH
United Kingdom

Trial participating centre

Hull Royal Infirmary
Anlaby Road
Hull
HU3 2JZ
United Kingdom

Trial participating centre

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

Trial participating centre

Royal London Hospital
Whitechapel
London
E1 1BB
United Kingdom

Trial participating centre

Bronglais General Hospital
Caradoc Road
Aberystwyth
SY23 1ER
United Kingdom

Trial participating centre

Altnagelvin Hospital
Glenshane Rd
Londonderry
BT47 6SB
United Kingdom

Trial participating centre

Prince Philip Hospital
Bryngwyn Mawr
Llanelli
SA14 8QF
United Kingdom

Trial participating centre

Poole Hospital
Longfleet Rd
Poole
BH15 2JB
United Kingdom

Trial participating centre

Morriston Hospital
Heol Maes Eglwys
Cwmrhydyceirw, Swansea
SA6 6NL
United Kingdom

Trial participating centre

Musgrove Park Hospital
Parkfield Dr
Taunton
TA1 5DA
United Kingdom

Trial participating centre

South West Acute Hospital
124 Irvinestown Rd
Enniskillen
BT74 6DN
United Kingdom

Trial participating centre

Glangwili Hospital
Dolgwili Rd
Carmarthen
SA31 2AF
United Kingdom

Trial participating centre

Princess Royal Hospital
Farnborough Common
Orpington
BR6 8ND
United Kingdom

Trial participating centre

James Cook University Hospital
Marton Rd
Middlesborough
TS4 3BW
United Kingdom

Trial participating centre

Royal Victoria Hospital
274 Grosvenor Rd
Belfast
BT12 6BA
United Kingdom

Trial participating centre

Royal Stoke University Hospital
Newcastle Rd
Stoke-on-Trent
ST4 6QG
United Kingdom

Trial participating centre

King's Mill Hospital
Mansfield Rd
Sutton-in-Ashfield
NG17 4JL
United Kingdom

Trial participating centre

Queen Elizabeth Hospital
Gayton Rd
King's Lynn
PE30 4ET
United Kingdom

Trial participating centre

Royal Devon & Exeter Hospital
Barrack Rd
Exeter
EX2 5DW
United Kingdom

Trial participating centre

Pinderfields Hospital
Aberford Road
Wakefield
WF1 4DG
United Kingdom

Trial participating centre

Salford Royal Hospital
Stott Lane
Salford
M6 8HD
United Kingdom

Trial participating centre

Royal Stoke Hospital
Newcastle Rd
Stoke-on-Trent
ST4 6QG
United Kingdom

Sponsor information

Organisation

University of Nottingham

Sponsor details

Research and innovation
East Atrium Jubilee Conference Centre
Jubilee Campus
Nottingham
NG8 1DH
United Kingdom
0115 846 7906
angela.shone@nottingham.ac.uk

Sponsor type

University/education

Website

http://www.nottingham.ac.uk/

Funders

Funder type

Not defined

Funder name

Efficacy and Mechanism Evaluation Programme

Alternative name(s)

NIHR Efficacy and Mechanism Evaluation Programme, EME

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Trial results will be published in a peer reviewed academic journal. The focus of the article will be to discuss the effectiveness and safety of RIC in ischaemic stroke. When the study is complete summary findings will be posted on the support group website. Findings will also be presented at conferences such as UK Stroke Forum, European Stroke Conference and World Stroke Congress.

IPD sharing statement:
All data will be stored on a secure dedicated web server. Access will be restricted by user identifiers and passwords (encrypted using a one way encryption method). Data will only be available to trial coordinating staff during the trial. Data used for publication will be anonymised.

Intention to publish date

01/12/2023

Participant level data

Not expected to be available

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

29/04/2020: The inclusion and exclusion criteria were updated. 14/04/2020: Trial's existence confirmed by the NIHR.