Table 2.

Summary of the major clinical trials of RIPerC and early RIPostC in acute stroke

Study	N	Population and timing	RIC protocol and duration	Control group	Primary outcome measure	Selected secondary outcome measures
RICAMIS (NCT03740971) China 2018–2020	1800	Acute moderate ischaemic stroke (NIHSS 6–16), confirmed on CT/MRI, and within 48 hours of symptom onset	5×5 mins (200 mm Hg) Bilateral UL Twice daily 10–14 days	Usual care	mRS at day 90	NIHSS day 12 Stroke associated pneumonia All-cause mortality day 90 Biomarkers (BDNF, VEGF, HIF-1α, TNF-α, IL-1β, IL-6)
RESIST (NCT03481777) Denmark 2018–24	1500	Acute ischaemic stroke and acute intracerebral haemorrhage, Prehospital Stroke Score ≥1* and within 4 hours of symptom onset. RIC commenced at prehospital phase with further cycles if confirmed stroke.	5×5 mins (200 mm Hg) Unilateral UL Twice daily Up to 7 days	Sham RIC at 20 mm Hg	mRS at day 90	Prehospital stroke score at 24 hours. All cause mortality at 1 year Biomarkers: nitric oxide synthase phosphorylation, microRNA and extracellular vesicle profile
SERIC-AIS (NCT03669653) China 2018–22	912	Clinical diagnosis of acute ischaemic stroke (NIHSS 5–25) and within 12 hours of symptom onset.	4×5 mins (200 mm Hg) UL Twice daily Up to 7 days	Sham RIC (60 mm Hg)	mRS day 90	NIHSS day 7 Inflammatory cytokines
REMOTE-CAT (NCT03375762) Spain 2019–22	572	Suspected clinical stroke (RACE scale >0 and RACE motor item >0) and within 8 hours of symptom onset.	5×5 mins Unspecified cuff pressure Non-paretic UL	Sham RIC (unspecified pressure)	mRS day 90	NIHSS day 5 Infarct volume (DWI MRI) Metabolomic and lipidomic biomarkers
REPOST (NTR6880) Netherlands 2018–2019	200	Clinical diagnosis of ischaemic stroke and within 12 hours of symptom onset	4×5 mins (20 mm Hg >SBP) Unilateral UL Twice daily Up to 4 days	Sham RIC at 50 mm Hg	Infarct size on DWI MRI at day 4/day of discharge if earlier	mRS at 12 weeks NIHSS at discharge SSQoL and TOPICS-SF at 12 weeks and 1-year serum biomarkers
RESCUE BRAIN (NCT02189928) France 2015–2019	200	Acute ischaemic stroke (NIHSS 5–25), confirmed on MRI and within 6 hours of symptom onset	4×5 mins (110 mm Hg >SBP) Unilateral LL Single treatment	Usual Care	Infarct growth on DWI MRI at 24 hours	NIHSS day 1 mRS and Barthel Index at 12 months Recanalisation rates after thrombolysis/thrombectomy

*The Prehospital Stroke Score is a combined score of the Cincinnati Prehospital Stroke Scale and Postural Assessment Scale for Stroke mRS.

BDNF, Brain-derived Neutrotrophic Factor; DWI, Diffusion Weighted Imaging; HIF-1a, Hypoxia-inducible Factor 1-alpha; IL-6, interleukin 6; mRS, modified Rankin Scale; NIHSS, National Institute of Health Stroke Scale; RACE, Rapid Arterial Occlusion Evaluation; RIC, remote ischaemic conditioning; SBP, systolic blood pressure; SSQoL, Stroke Specific Quality of Life Scale; SSQoL, Stroke Specific Quality of Life; TNFα, tumour necrosis factor-α; TOPICS-SF, The Older Persons and Informal Caregivers Short Form; TOPICS-SF, The Older Persons and Informal Caregivers Survey Short Form; VEGF, Vascular Endothelial Growth Factor.