Effect of In-Hospital Remote Ischemic Perconditioning on Brain Infarction Growth and Clinical Outcomes in Patients With Acute Ischemic Stroke: The RESCUE BRAIN Randomized Clinical Trial.

Importance: Treatment with remote ischemic perconditioning has been reported to reduce brain infarction volume in animal models of stroke. Whether this neuroprotective effect was observed in patients with acute ischemic stroke remains unknown. Objective: To determine whether treatment with remote ischemic perconditioning administered to the leg of patients with acute ischemic stroke can reduce brain infarction volume growth. Design, Setting, and Participants: This proof-of-concept multicenter prospective randomized open-label with blinded end point clinical trial was performed from January 12, 2015, to May 2, 2018. Patients were recruited from 11 stroke centers in France. Of the 188 patients who received magnetic resonance imaging within 6 hours of symptom onset and were confirmed to have carotid ischemic stroke, 93 were randomized to receive treatment with lower-limb remote ischemic perconditioning in addition to standard care (the intervention group), and 95 were randomized to receive standard care alone (the control group). Interventions: Randomization on a 1:1 ratio to receive treatment with remote ischemic perconditioning (4 cycles of 5-minute inflations and 5-minute deflations to the thigh to 110 mm Hg above systolic blood pressure) in addition to standard care or standard care alone. Main Outcomes and Measures: The change in brain infarction volume growth between baseline and 24 hours, measured by a diffusion-weighted sequence of magnetic resonance imaging scans of the brain. Results: A total of 188 patients (mean [SD] age, 67.2 [15.7] years; 98 men [52.1%]) were included in this intention-to-treat analysis. At hospital admission, the median National Institutes of Health Stroke Scale score was 10 (interquartile range [IQR], 6-16) and the median brain infarction volume was 11.4 cm3 (IQR, 3.6-35.8 cm3); 164 patients (87.2%) received intravenous thrombolysis, and 64 patients (34.0%) underwent mechanical thrombectomy. The median increase in brain infarction growth was 0.30 cm3 (IQR, 0.11-0.48 cm3) in the intervention group and 0.37 cm3 (IQR, 0.19-0.55 cm3) in the control group (mean between-group difference on loge-transformed change, -0.07; 95% CI, -0.33 to 0.18; P = .57). An excellent outcome (defined as a score of 0-1 on the 90-day modified Rankin Scale or a score equal to the prestroke modified Rankin Scale score) was observed in 46 of 90 patients (51.1%) in the intervention group and 37 of 91 patients (40.7%) in the control group (P = .12). No significant differences in 90-day mortality were observed between the intervention and control groups (14 of 90 patients; Kaplan-Meier estimate, 15.8% vs 10 of 91 patients; Kaplan-Meier estimate, 10.4%, respectively; P = .45) or with symptomatic intracerebral hemorrhage (4 of 88 patients [4.5%] in both groups; P = .97). Conclusions and Relevance: In this study, treatment with remote ischemic perconditioning, during or after reperfusion therapies, had no significant effect on brain infarction volume growth at 24 hours after symptom onset. Trial Registration: ClinicalTrials.gov Identifier: NCT02189928.

A multicenter, randomized trial on neuroprotection with remote ischemic per-conditioning during acute ischemic stroke: the REmote iSchemic Conditioning in acUtE BRAin INfarction study protocol.

Rationale Remote ischemic per-conditioning-causing transient limb ischemia to induce ischemic tolerance in other organs-reduces final infarct size in animal stroke models. Aim To evaluate whether remote ischemic per-conditioning during acute ischemic stroke (<6 h) reduces brain infarct size at 24 h. Methods and design This study is being performed in five French hospitals using a prospective randomized open blinded end-point design. Adults with magnetic resonance imaging confirmed ischemic stroke within 6 h of symptom onset and clinical deficit of 5-25 according to National Institutes of Health Stroke Scale will be randomized 1:1 to remote ischemic per-conditioning or control (stratified by center and intravenous fibrinolysis use). Remote ischemic per-conditioning will consist of four cycles of electronic tourniquet inflation (5 min) and deflation (5 min) to a thigh within 6 h of symptom onset. Magnetic resonance imaging is repeated 24 h after stroke onset. Sample size estimates For a difference of 15 cm3 in brain infarct growth between groups, 200 patients will be included for 5% significance and 80% power. Study outcomes The primary outcome will be the difference in brain infarct growth from baseline to 24 h in the intervention versus control groups (by diffusion-weighted image magnetic resonance imaging). Secondary outcomes include: National Institutes of Health Stroke Scale score absolute difference between baseline and 24 h, three-month modified Rankin score and daily living activities, mortality, and tolerance and side effects of remote ischemic per-conditioning. Discussion The only remote ischemic per-conditioning trial in humans with stroke did not show remote ischemic per-conditioning to be effective. REmote iSchemic Conditioning in acUtE BRAin INfarction, which has important design differences, should provide more information on the use of this intervention in patients with acute ischemic stroke.