Article Figures & Data
- Figure 1
Model of remote ischaemic conditioning.
- Figure 2
A schematic of RIC timing and duration in major trials of acute stroke. RIC, remote ischaemic conditioning.
- Figure 3
Proposed mechanism of action of remote ischaemic conditioning in stroke.
- Figure 4
Optimising remote ischaemic conditioning (RIC) trial design. AIS, Acute Ischaemic Stroke; ET, endovascular therapy; ICH, Intracerebral haemorrhage; SAH, Subarachnoid Haemorrhage; tPA, Tissue Plasminogen Sctivator.
- Table 1
Summary characteristics of ongoing trials of RIC in stroke
Parameter No of studies Study population Ischaemic stroke/TIA 31 Symptomatic intracranial stenosis 8 Aneurysmal subarachnoid haemorrhage 4 Unruptured cerebral aneurysm 3 Intracerebral haemorrhage 3 Timing of conditioning RIPreC 3 RIPerC and early RIPostC 28 Chronic RIPostC 16 Unspecified 1 Participants (N) <100 24 100–500 17 501–1000 4 >1000 3 RIC protocol Cuff pressure 180 mm Hg 2 200 mm Hg 26 225 mm Hg 2 20 mm Hg >SBP 4 30 mm Hg >SBP 2 50 mm Hg >SBP 1 110 mm Hg >SBP 1 Variable 1 Unspecified 9 Cycle length 3 min 1 5 min 36 10 min 1 Variable 1 Unspecified 9 Cycle frequency 3 5 4 16 5 19 Variable 1 Unspecified 7 Limb Upper 36 Lower 5 Unspecified 7 Unilateral 18 Bilateral 16 Unspecified 14 Study location Asia 30 Europe 10 North America 8 Primary outcome measures Clinical modified Rankin Scale 6 Compliance/feasibility 6 Adverse events 6 Recurrent stroke 4 Combined vascular events 1 All-cause mortality 1 NIHSS 1 Walking speed 1 Depression incidence 1 Blood samples Serum biomarkers 5 Immune profile 2 Coagulation profile 1 Radiological Infarct size/growth 6 New infarcts 2 Cerebral blood flow/collateral circulation 3 Vasospasm 2 Flow-mediated dilatation 1 Other P300 event-related potential 1 Cardiac function (echocardiogram) 1 Estimated study completion 2019 11 2020 10 2021 8 2022 5 2023 0 2024 3 RIC, remote ischaemic conditioning; RIPerC, Remote ischaemic perconditioning; RIPostC, Remote ischaemic postconditioning; RIPreC, Remote ischaemic preconditioning; SBP, systolic blood pressure; TIA, Transient Ischaemic Attack.
- 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
2018–20201800 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 daysUsual 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
2018–241500 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 daysSham 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 profileSERIC-AIS
(NCT03669653)
China
2018–22912 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 daysSham RIC (60 mm Hg) mRS day 90 NIHSS day 7
Inflammatory cytokinesREMOTE-CAT
(NCT03375762)
Spain
2019–22572 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 ULSham RIC (unspecified pressure) mRS day 90 NIHSS day 5
Infarct volume (DWI MRI)
Metabolomic and lipidomic biomarkersREPOST (NTR6880)
Netherlands
2018–2019200 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 daysSham 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 biomarkersRESCUE BRAIN
(NCT02189928)
France
2015–2019200 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 treatmentUsual 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.
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