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 48 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 4 and 25 (inclusive) at time of randomisation
At least 18 years old
Mechanical thrombectomy sub-study only
- Selected sites only
- Randomised and received mechanical thrombectomy up to 24 hours post-onset

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 or pre-existing condition of the upper limbs, which in the opinion of the investigator, will be exacerbated by remote ischaemic conditioning
Expected repatriation less than 72 hours of the participant to another hospital not participating in ReCAST-3, where RIC or sham cannot continue
Mechanical thrombectomy sub-study 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: