Remote ischaemic Conditioning After Stroke Trial (ReCAST)
| ISRCTN | ISRCTN86672015 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN86672015 |
| ClinicalTrials.gov number | NCT02779712 |
| Secondary identifying numbers | 13466 |
- Submission date
- 28/11/2012
- Registration date
- 29/11/2012
- Last edited
- 28/08/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Circulatory System
Plain English summary of protocol
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 patients 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 (UK)
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?
British Medical Association (UK)
Who is the main contact?
Dr T. England
timothy.england@nottingham.ac.uk
Contact information
Scientific
Division of Stroke Medicine
The University of Nottingham
Clinical Sciences Building
Hucknall Road
Nottingham
NG5 1PB
United Kingdom
| timothy.england@nottingham.ac.uk |
Study information
| Study design | Randomised interventional trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Remote ischaemic Conditioning After Stroke Trial (ReCAST): a randomised controlled trial |
| Study acronym | ReCAST |
| Study objectives | 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 bodys 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. |
| Ethics approval(s) | NRES Committee West Midlands Staffordshire, 19/12/2012, ref:12/WM/0339 |
| Health condition(s) or problem(s) studied | 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 |
| Primary outcome measure | 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 study start date | 04/03/2013 |
| Completion date | 03/12/2015 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 30; UK Sample Size: 30 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 04/03/2013 |
| Date of final enrolment | 03/12/2015 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
NG5 1PB
United Kingdom
Sponsor information
University/education
Hayward House Macmillan Specialist Palliative Care Unit
Hucknall Road
Nottingham
NG5 1PB
England
United Kingdom
| Sponsor@nottingham.ac.uk | |
| Website | http://www.nottingham.ac.uk |
"ROR" |
https://ror.org/01ee9ar58 |
Funders
Funder type
Other
Private sector organisation / Associations and societies (private and public)
- Alternative name(s)
- BMA
- Location
- United Kingdom
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/05/2017 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
28/08/2019: ClinicalTrials.gov number added.
08/03/2017: Publication reference added.
