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.