title: 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.
abstract: 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 cm3in 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.
authors.affiliation: 1 Neurology Department and Stroke Centre, Centre Hospitalier de Versailles, Le Chesnay, France.|2 Université de Versailles Saint-Quentin-en-Yvelines, Versailles, France.|3 INSERM LVTS (Laboratory for Vascular Translational Science)-1148, Paris, France.
authors.forename: Fernando
authors.initials: F
authors.lastname: Pico
authors.affiliation: 4 AP-HP, Urgences Cerebro-Vasculaires, Pitié-Salpêtrière Hospital, Paris, France.|5 UPMC, Univ Paris 06, Centre de Recherche de l'Institut du Cerveau et de la Moëlle épinière, Paris, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Rosso
authors.affiliation: 6 Department of Neurology and Stroke Centre, AP-HP Bichat University Hospital, Paris-Diderot University and Medical School, Paris, France.
authors.forename: Elena
authors.initials: E
authors.lastname: Meseguer
authors.affiliation: 1 Neurology Department and Stroke Centre, Centre Hospitalier de Versailles, Le Chesnay, France.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Chadenat
authors.affiliation: 7 Versailles Délégation à la Recherche Clinique (DRCI), Mignot Hospital, Le Chesnay, France.
authors.forename: Amina
authors.initials: A
authors.lastname: Cattenoy
authors.affiliation: 8 Department Santé Publique et Unité de Recherche Clinique, AP-HP, Hôpital A Paré, Boulogne, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Aegerter
authors.affiliation: 4 AP-HP, Urgences Cerebro-Vasculaires, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Deltour
authors.affiliation: 1 Neurology Department and Stroke Centre, Centre Hospitalier de Versailles, Le Chesnay, France.|2 Université de Versailles Saint-Quentin-en-Yvelines, Versailles, France.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Yeung
authors.affiliation: 9 Stroke Center Mondor Hospital and School of Medicine, Créteil, France.
authors.forename: Hassan
authors.initials: H
authors.lastname: Hosseini
authors.affiliation: 10 SAMU 78, Centre Hospitalier de Versailles, Le Chesnay, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Lambert
authors.affiliation: 11 Stroke Center Sud Francilien Hospital, Evry, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Smadja
authors.affiliation: 4 AP-HP, Urgences Cerebro-Vasculaires, Pitié-Salpêtrière Hospital, Paris, France.|5 UPMC, Univ Paris 06, Centre de Recherche de l'Institut du Cerveau et de la Moëlle épinière, Paris, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Samson
authors.affiliation: 3 INSERM LVTS (Laboratory for Vascular Translational Science)-1148, Paris, France.|6 Department of Neurology and Stroke Centre, AP-HP Bichat University Hospital, Paris-Diderot University and Medical School, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Amarenco
mesh_terms: D001921:Brain / Q000000981:diagnostic imaging; D002545:Brain Ischemia / Q000000981:diagnostic imaging / Q000628:therapy*; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D005602:France; D006801:Humans; D057775:Ischemic Postconditioning; D008279:Magnetic Resonance Imaging; D018401:Sample Size; D020521:Stroke / Q000000981:diagnostic imaging / Q000628:therapy*; D013848:Thigh / Q000098:blood supply*; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents
keywords: Remote ischemic per-conditioning; diffusion-weighted image magnetic resonance imaging; infarct size; ischemic stroke; neuroprotection