Condition category
Circulatory System
Date applied
28/11/2012
Date assigned
29/11/2012
Last edited
01/07/2013
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Stroke is the third leading cause of death worldwide and is devastating to both patients and carers. In the United Kingdom there are 110,000 first strokes and 30,000 recurrent strokes each year, which consumes up to 6% of NHS resources. There are only a few effective treatments for stroke and recent research has failed to demonstrate effectiveness of novel drug treatments, therefore, new approaches to reduce the burden of stroke on society are required.
The concept of ischaemic conditioning (IC) is an approach used to protect organs/tissue from something called ischaemia/reperfusion injury (the injury a tissue sustains as a result of reestablishing its blood flow after it has been blocked). Remote ischaemic conditioning (RIC) means briefly interrupting the blood supply to an area (i.e. the arm) distant from an organ you are trying to protect (i.e. the brain). Experiments in animals have shown RIC to protect the brain from injury caused by a stroke when RIC is applied soon after the stroke has occurred. In people, RIC can be achieved by inflating a blood pressure (BP) cuff on the arm several times very soon after a stroke. RIC is already used during cardiac surgery and it may help protect the heart after a heart attack. In a recent study of 333 patients with a heart attack, RIC applied by paramedics, whilst the patient was still in the ambulance, helped to decrease the amount of damage to the heart and had a favourable safety profile.
RIC is an attractive prospect in the clinical setting since it bears little cost and would be simple to administer by medics and allied health professionals (nurses, paramedics) and could be applied very quickly. A typical protocol would involve inflating a blood pressure cuff, applied to a patient’s upper arm, to a level exceeding their current blood pressure, for a period of 5 minutes. This would then be repeated 4 times.
We therefore plan to commence an initial small study evaluating the tolerability, feasibility and safety of RIC in patients with very early stroke.

Who can participate?
We will recruit 30 patients from the Royal Derby Hospital Stroke Unit over 15 months (2 per month).

What does the study involve?
Patients will be randomly allocated to the intervention or sham procedure. The intervention will be 4 cycles RIC (alternating 5 minutes inflation, 5 minutes deflation of a standard upper arm BP cuff), applied within 12 hours of stroke onset. Patients randomised to the sham procedure will receive 4 cycles of BP cuff inflation (up to 30mmHg a very low level that will not obstruct the blood supply to the limb) and deflation.

What are the possible benefits and risks of participating?
The results will inform the design of future trials of a potential intervention that is practical, noninvasive and simple to administer.
Risks: discomfort or pins and needles when the blood pressure cuff is inflated.

Where is the study run from?
Royal Derby Hospital Stroke Unit

When is the study starting and how long is it expected to run for?
The study will commence in March 2013 and will run for 2 years.

Who is funding the study?
The trial is funded by the British Medical Association

Who is the main contact?
Dr T. England
timothy.england@nottingham.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Timothy England

ORCID ID

Contact details

Division of Stroke Medicine
The University of Nottingham
Clinical Sciences Building
Hucknall Road
Nottingham
NG5 1PB
United Kingdom
timothy.england@nottingham.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

13466

Study information

Scientific title

Remote ischaemic Conditioning After Stroke Trial (ReCAST): a randomised controlled trial

Acronym

ReCAST

Study hypothesis

Stroke has an enormous impact on both individual and society. Novel treatments are required to relieve this burden and remote ischaemic conditioning (RIC) is one such approach. RIC means briefly interrupting the blood supply to an area (i.e. the arm) distant from an organ you are trying to protect (i.e. the brain). Experiments in animals have shown RIC to protect the brain from injury caused by stroke. In humans, RIC could be achieved by inflating a blood pressure cuff on the arm several times very soon after a stroke. The mechanisms of protection are unclear but may be due enhancing the body’s ability to protect itself by altering the blood flow to the brain or by reducing the harmful effects of inflammation. RIC is already used during cardiac surgery and it may help protect the heart after a heart attack. We plan to conduct a pilot clinical trial assessing the tolerability and feasibility of RIC patients after stroke, whilst investigating how it might work. The results will inform the design of future trials of a potential intervention is that is pragmatic, noninvasive and simple to administer.

More details can be found at: http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=13466

Ethics approval

NRES Committee West Midlands – Staffordshire, 19th December 2012, ref:12/WM/0339

Study design

Randomised interventional trial

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

Topic: Stroke Research Network; Subtopic: Acute Care; Disease: Device used

Intervention

30 patients will be randomised on a 1:1 basis to receive either:
Remote ischaemic conditioning (RIC group): 4 cycles of intermittent limb ischaemia - alternating 5 minutes inflation (up to 20mmHg above systolic BP) followed by 5 minutes deflation of a standard upper arm blood pressure cuff in the non-paretic arm; or
Control group: 4 cycles of inflation and deflation up to 30mmHg in the non-paretic arm
Follow up on Day 4 and Day 90.

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

Tolerability (duration cuff tolerated, number of cycles, drop out rate) and feasibility (accrual rate, proportion of patients knowing if they received RIC or sham) of RIC after hyperacute ischaemic stroke

Secondary outcome measures

Clinical safety (day 4±1, day 90±7):
Serious adverse events (SAE); death (cause); recurrence/progression; neurological deterioration (increase in NIHSS >4 points); vascular events (including limb ischaemia, venous thrombo-embolism); neurovascular limb damage and tissue injury.

Laboratory measures: (Day 0, day 4±1, day 90±7)
Surrogate markers of efficacy, plasma S100B and MMP-9 levels by multiplex analysis; markers of inflammation and vascular function including but not limited to plasma CRP, e-selectin and vCAM by multiplex analysis; circulating endocannabinoids levels; plasma SOD activity by bioassay.

Haemodynamic parameters:
Transcranial Doppler (TCD), continuous recording during RIC, measures middle cerebral artery blood flow velocity/pulsatility index (a surrogate for cerebral blood flow (CBF)). Day 0 pre and post RIC, day 4±1 and day 90±7: central BP, pulse pressure, heart rate, rate-pressure product; aortic compliance and pulse wave velocity.

Clinical efficacy: (Day 4±1, day 90±7)
Impairment (NIHSS, motoricity index); dependency (modified Rankin Scale (mRS)); disability (Barthel Index(BI)<60)); functional independence (extended activities of daily living (EADL)); Zung depression scale; cognition (MMSE). At discharge/death: Length of stay in hospital; discharge disposition.

Overall trial start date

04/03/2013

Overall trial end date

03/12/2015

Reason abandoned

Eligibility

Participant inclusion criteria

1. Age > 18 years
2. Clinical stroke (lacunar or cortical) of ischaemic subtype
3. Within 12 hours of stroke onset
4. Arm and/or leg weakness at the time of randomisation

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 30; UK Sample Size: 30

Participant exclusion criteria

1. Premorbid dependency, modified Rankin scale (mRS) >3
2. Known subclavian or brachial artery stenosis
3. Dementia
4. Coma [Glasgow Coma Scale (GCS< 8)]
5. Malignancy or significant comorbidity
6. Participation in other drug trials
7. Pregnancy

Recruitment start date

04/03/2013

Recruitment end date

03/12/2015

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Division of Stroke Medicine
Nottingham
NG5 1PB
United Kingdom

Sponsor information

Organisation

University of Nottingham (UK)

Sponsor details

Hayward House Macmillan Specialist Palliative Care Unit
Hucknall Road
Nottingham
NG5 1PB
United Kingdom
Sponsor@nottingham.ac.uk

Sponsor type

University/education

Website

http://www.nottingham.ac.uk

Funders

Funder type

Other

Funder name

British Medical Association (BMA) (UK)

Alternative name(s)

BMA

Funding Body Type

private sector organisation

Funding Body Subtype

professional associations and societies

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