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Original Investigation
March 30, 2020

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

Author Affiliations
  • 1Department of Neurology and Stroke Center, Versailles Mignot Hospital, Versailles, France
  • 2University of Versailles Saint-Quentin-en-Yvelines and Paris-Saclay University, Saint-Aubin, France
  • 3Laboratoire de Recherche Vasculaire Translationnelle, Inserm U1148, Paris, France
  • 4Neurology and Stroke Center, Hôpital Foch, Suresnes, France
  • 5Department of Degenerative and Vascular Cognitive Disorders, Inserm U1171, Université de Lille, Lille, France
  • 6Department of Neurology, Centre Hospitalier Universitaire de Lille, Lille, France
  • 7Assistance Publique-Hopitaux de Paris, Service des Urgences Cerebro-Vasculaires, Hôpital Pitié-Salpêtrière, Paris, France
  • 8Centre National de la Recherche Scientifique, Inserm U1127, Unite Mixte de Recherche 7225, Institut du Cerveau et de la Moelle Epiniere, Sorbonne Universite, Paris, France
  • 9Assistance Publique-Hôpitaux de Paris, Department of Neurology and Stroke Center, Bichat University Hospital, Universite Paris Diderot, Sorbonne Cite, Paris, France
  • 10Neurology and Stroke Center, Fondation Ophtalmologique Adolphe de Rothschild, Paris, France
  • 11Assistance Publique-Hôpitaux de Paris, Vieillissement et Maladies Chroniques, IndianaSERM, Unité Mixte de Recherche 1168, Universite de Versailles Saint-Quentin-en-Yvelines, Versailles, France
  • 12Department of Biostatistics, Université de Lille, Lille, France
  • 13Unité de Recherche EA 2694–Sante Publique: Epidemiologie et Qualite des Soins, Centre Hospitalier Universitaire de Lille, Lille, France
  • 14Délégation à la Recherche Clinique, Versailles Mignot Hospital, Versailles, France
  • 15Stroke Unit, Centre Hospitalier Sud Francilien, Corbeil-Essonnes, France
  • 16Assistance Publique-Hopitaux de Paris, Stroke Center, Henri Mondor Hospital, Université Paris-Est Créteil, Creteil, France
  • 17Department of Neurology, University Hospital of Nantes, Nantes, France
  • 18Stroke Unit, Strasbourg University Hospital, Strasbourg, France
JAMA Neurol. 2020;77(6):725-734. doi:10.1001/jamaneurol.2020.0326
Key Points

Question  Does treatment with remote ischemic perconditioning reduce brain infarction volume growth in patients with acute ischemic stroke?

Findings  In this randomized clinical trial of 188 patients with acute ischemic stroke, brain infarction volume was used as an outcome measure. Treatment with remote ischemic perconditioning within 6 hours of symptom onset was found not to reduce brain infarction volume growth.

Meaning  Contrary to the observations reported in preclinical studies, treatment with in-hospital remote ischemic perconditioning (in addition to reperfusion therapies) did not reduce brain infarction volume growth.


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

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    1 Comment for this article
    Narayanaswamy Venketasubramanian, MBBS | Raffles Hispital
    I wonder if the term 'para-conditioning' would more accurately describe the timing of this intervention than 'perconditioning', as it is done during the ischaemia. This will fit in well with the terms 'pre-conditioning' and 'post-conditioning' as these are done before and after the ischaemic event respectively.