ReCAST-3

Title	Remote ischaemic Conditioning After Stroke Trial 3 (ReCAST-3)
Acronym	ReCAST-3
Chief investigator	Dr Tim England
Aim	To perform a multicentre randomised controlled trial assessing remote ischaemic conditioning (RIC) in patients with acute ischaemic stroke.
Trial configuration	Phase III prospective randomised (1:1) sham-controlled blinded-endpoint parallel-group multicentre trial.
Setting	Adults with acute ischaemic stroke presenting in emergency departments and stroke units in the UK.
Sample size estimate	Assuming alpha=0.05, power=90%, losses to follow up=5% and covariate adjustment reducing sample size by 20%, a sample size of 1,300 will be needed to detect a treatment effect of OR 0.75 by shift analysis of mRS.
Number of participants	1,300
Eligibility criteria	Inclusions Acute ischaemic stroke, within 24 hours of onset Spontaneous intracerebral haemorrhage ruled out on baseline clinical neuroimaging Haemorrhagic transformation of infarction (HTI) HI1, HI2, PH1 is permitted NIHSS score between 5 and 25 (inclusive) at time of randomisation At least 18 years old Exclusions Pre-morbid dependency (modified Rankin Scale of 4 or 5) Spontaneous intracerebral haemorrhage Systolic blood pressure below 80 mmHg Haemorrhagic transformation of infarction PH2 (haematoma occupying 30% or more of the infarcted tissue, with obvious mass effect) Pre-existing diagnosis of dementia Coma (Glasgow Coma Scale below 8) Malignancy Significant co-morbidity (life expectancy of less than 6 months) Glucose (BM stix or equivalent) less than 3 mmol/L Known pregnancy Taking part in another interventional trial, unless co-enrolment has been approved by both chief investigators and sponsor (co-enrolment in observational studies is generally accepted) Seizure on presentation unless brain imaging identifies evidence of significant brain ischaemia (early ischaemic change or hyperdense vessel on CT scan, or angiography confirmed arterial occlusion) Significant tissue injury of the upper limbs, which in the opinion of the investigator, will be exacerbated by remote ischaemic conditioning Expected repatriation of the participant to another hospital not participating in ReCAST-3, where RIC or sham cannot continue Mechanical thrombectomy substudy only Known contra-indication to administration of IV contrast (required for a CT Perfusion scan). This may include previous allergic reaction to contrast or considered high risk for contrast induced nephropathy (at the discretion of the investigator). This does not exclude them from the main trial.
Description of interventions	Remote ischaemic conditioning 4 cycles of intermittent upper limb ischaemia – alternating 5 minutes inflation (+20 mmHg above systolic BP), followed by 5 minutes deflation of bilateral upper arm blood pressure cuffs. Sham procedure Bilateral upper arm blood pressure cuffs are inflated to 50 mmHg for 4 cycles (5 minutes inflation/5 minutes deflation).
Duration of study	Total trial duration 45 months. Participant duration: 90±7 days.
Randomisation and blinding	Web based randomisation will occur immediately after consent, performed by the clinician taking consent. Randomisation will be 1:1 RIC: placebo, minimised on baseline prognostic factors. Follow-up measures will be performed by assessors blinded to treatment allocation
Outcome measures	Primary outcome: Death or dependency at day 90 (modified Rankin Scale [mRS], ordinal shift analysis) recorded using central blinded telephone follow-up. Secondary outcomes (day 90): Cerebrovascular events; major adverse cardiac and cerebral events; acute kidney injury; COVID-19 status; disability; cognition; mood; frailty; quality of life; safety (death; neurological deterioration; intracranial haemorrhage, systemic embolism, serious adverse events). Mechanisms: Mechanical thrombectomy sub-study (day 2-14 MRI; infarct growth and volume, oedema, perfusion).

Contact details
Address:	Room S/D2108 Stroke Trials Unit School of Medicine University of Nottingham Queen's Medical Centre Derby Road Nottingham NG7 2UH United Kingdom Tel: 0115 823 1770
Email:

ReCAST-3 trial

Remote ischaemic Conditioning After Stroke Trial 3