Remote Ischaemic Conditioning After Stroke Trial (ReCAST-2)

Study Overview
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Brief Summary
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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 refers to applying non-lethal ischaemia to an area distant from an organ you are trying to protect (e.g. the brain). Pre-clinical animal stroke studies have shown RIC to be neuroprotective and help restore functional outcome when compared to control. These outcomes are achieved simply by transiently occluding the blood supply to a limb (e.g. the arm) very soon after the stroke occurs. The mechanisms of protection are unclear but may be due enhancing the body's ability to protect itself from further injury by favorably altering cerebral blood flow or reducing the detrimental effects of oxygen free radicals. Ischaemic conditioning (IC) is an intervention already applied during cardiac surgery to protect the heart from damage and it may be effective after an acute myocardial infarction. The investigators therefore plan to conduct a pilot randomised controlled trial assessing the feasibility of applying RIC (4 cycles of blood pressure cuff inflation for 5 minutes) in patients within 6 hours of ischaemic stroke. The primary outcome is feasibility of RIC. Secondary outcomes include tolerability, safety and clinical efficacy. The results will inform the design of future trials of a potential intervention is that is pragmatic, non-invasive and simple to administer.

Official Title
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Remote Ischaemic Conditioning After Stroke Trial (ReCAST-2): A Pilot Randomised Controlled Phase II Trial Evaluating Remote Ischaemic Conditioning (RIC) After Hyperacute Stroke 2

Conditions
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Stroke

Intervention / Treatment
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* Procedure: Remote ischaemic conditioning
* Procedure: Sham


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Suspected clinical stroke with 6 hours of onset of neurological symptoms; Age >18; Written or witnessed oral consent, or relative/consultee advice. Exclusion Criteria: Pre-morbid dependency mRS>3; Dementia; Coma (GCS< 8); Malignancy or significant co-morbidity thought to limit life expectancy to <6 months; Blood sugar < 3.5 mmol/L; Taking part in another clinical trial of an investigational medicinal product (CTIMP); Pregnancy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Remote Ischaemic Conditioning<br>Remote ischaemic conditioning (RIC group): 4 cycles of intermittent limb ischaemia - alternating 5 minutes inflation (20mmHg above systolic BP) followed by 5 minutes deflation of a standard upper arm blood pressure cuff | Procedure: Remote ischaemic conditioning<br>* 1 dose (=4 cycles) of intermittent upper limb ischaemia (1 cycle = 5minutes inflation to 20mmHg above systolic BP, 5 minutes deflation). Dose escalation: (i) Recruits 1-20 receive this cycle once (ii) Recruits 21-40 receive a second dose of 4-cycles one hour after the first. (iii) Recruits 41-60 receive further dosing, twice daily until day 4.<br>|
| Sham Comparator: Control<br>Control: 4 cycles of alternating 5 minutes inflation (up to 30 mmHg) followed by 5 minutes deflation of a standard upper arm blood pressure cuff | Procedure: Sham<br>* 4 cycles of intermittent sham procedure (1 cycle = 5 minutes inflation to 30 mmHg, 5 minutes deflation), matching the dose escalation described in the intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trial feasibility | Recruitment feasibility (recruitment rate) | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vascular Event Rate [Safety and Tolerability] | Number of participants with a vascular event (including limb ischaemia, recurrent stroke, myocardial infarction, venous thrombo-embolism) | Day 1, Day 4±1, day 90±7 | 
| Treatment Related Serious Adverse Event Rates [Safety and Tolerability] | Number of participants with a serious adverse event related to treatment | Day 1, Day 4±1, day 90±7 | 
| Biomarkers | Plasma S100-beta protein | Immediately before RIC/sham at baseline; immediately after RIC/sham on Day 1; day 4±1 | 
| Biomarkers | Plasma heat-shock proteins | Immediately before RIC/sham at baseline; immediately after RIC/sham on Day 1; day 4±1 | 
| Biomarkers | Plasma cytokines | Immediately before RIC/sham at baseline; immediately after RIC/sham on Day 1; day 4±1 | 
| Impairment | National Institutes of Health Stroke Scale | Day 4±1, day 90±7 | 
| Dependency | Modified Rankin scale | Day 90±7 | 
| Disability | Barthel Index | Day 90±7 | 
| Mood | Zung depression scale | Day 90±7 | 
| Telephone cognition | Modified Telephone Interview for Cognitive Status (TICS-M) | Day 90±7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Remote ischaemic conditioning