Norbert Nighoghossian1, Yves Berthezène1, Laura Mechtouff1, Laurent Derex1, Tae Hee Cho1, Thomas Ritzenthaler1, Sylvain Rheims1, Fabien Chauveau1, Yannick Béjot1, Agnès Jacquin1, Maurice Giroud1, Frédéric Ricolfi1, Frédéric Philippeau1, Catherine Lamy1, Guillaume Turc1, Eric Bodiguel1, Valérie Domigo1, Vincent Guiraud1, Jean-Louis Mas1, Catherine Oppenheim1, Pierre Amarenco1, Serkan Cakmak1, Mathieu Sevin-Allouet1, Benoit Guillon1, Hubert Desal1, Hassan Hosseini1, Igor Sibon1, Marie-Hélène Mahagne1, Elodie Ong1, Nathan Mewton1, Michel Ovize2. 1. From the Departments of Neurology (N.N., L.M., L.D., T.H.C., T.R., S.R., E.O.) and Neuroradiology (Y. Berthezène, F.C.), Hôpital Neurologique Pierre Wertheimer, Creatis CNRS UMR 5220, INSERM U1044, Université Lyon 1, INSA Lyon; Dijon Stroke Registry (Y. Béjot, A.J., M.G., F.R.) (EA 4184, Inserm, Invs), University Hospital of Dijon, Regional Council and University of Burgondy, CHU le Bocage, Dijon; Department of Neurology (F.P.), Centre Hospitalier de Fleyriat, Bourg en Bresse; Departments of Neurology (C.L., G.T., E.B., V.D., V.G., J.-L.M.) and Neuroradiology (C.O.), CH Sainte-Anne, University Paris-Descartes, INSERM U894, DHU NeuroVasc Sorbonne Paris Cité; Department of Neurology (P.A.), Hôpital Bichat-Claude Bernard, Paris; Department of Neurology (S.C.), Hôpital Nord-Ouest, Plateau d'Ouilly, Villefranche sur Saône; Department of Neurology (M.S.-A., B.G., H.D.), Hôpital Nord-Laënnec, Saint-Herblain; Department of Neurology (H.H.), Hôpital Henri Mondor, Créteil; Department of Neurology (I.S.), Groupe Hospitalier Pellegrin, Place Amélie Raba-Léon, Bordeaux; Unité Neurosciences (M.-H.M.), Hôpital Saint Roch, Nice; Hôpital Louis Pradel (N.M., M.O.), Service d'Explorations Fonctionelles Cardiovasculaires, Centre d'Investigation Clinique & UMR1060 (CarMeN), Université Claude Bernard Lyon 1, France. 2. From the Departments of Neurology (N.N., L.M., L.D., T.H.C., T.R., S.R., E.O.) and Neuroradiology (Y. Berthezène, F.C.), Hôpital Neurologique Pierre Wertheimer, Creatis CNRS UMR 5220, INSERM U1044, Université Lyon 1, INSA Lyon; Dijon Stroke Registry (Y. Béjot, A.J., M.G., F.R.) (EA 4184, Inserm, Invs), University Hospital of Dijon, Regional Council and University of Burgondy, CHU le Bocage, Dijon; Department of Neurology (F.P.), Centre Hospitalier de Fleyriat, Bourg en Bresse; Departments of Neurology (C.L., G.T., E.B., V.D., V.G., J.-L.M.) and Neuroradiology (C.O.), CH Sainte-Anne, University Paris-Descartes, INSERM U894, DHU NeuroVasc Sorbonne Paris Cité; Department of Neurology (P.A.), Hôpital Bichat-Claude Bernard, Paris; Department of Neurology (S.C.), Hôpital Nord-Ouest, Plateau d'Ouilly, Villefranche sur Saône; Department of Neurology (M.S.-A., B.G., H.D.), Hôpital Nord-Laënnec, Saint-Herblain; Department of Neurology (H.H.), Hôpital Henri Mondor, Créteil; Department of Neurology (I.S.), Groupe Hospitalier Pellegrin, Place Amélie Raba-Léon, Bordeaux; Unité Neurosciences (M.-H.M.), Hôpital Saint Roch, Nice; Hôpital Louis Pradel (N.M., M.O.), Service d'Explorations Fonctionelles Cardiovasculaires, Centre d'Investigation Clinique & UMR1060 (CarMeN), Université Claude Bernard Lyon 1, France. michel.ovize@chu-lyon.fr.
Abstract
OBJECTIVES: We examined whether IV administration of cyclosporine in combination with thrombolysis might reduce cerebral infarct size. METHODS:Patients aged 18 to 85 years, presenting with an anterior-circulation stroke and eligible for thrombolytic therapy, were enrolled in this multicenter, single-blinded, controlled trial. Fifteen minutes after randomization, patients received either an IV bolus injection of 2.0 mg/kg cyclosporine (Sandimmune, Novartis) or placebo. The primary endpoint was infarct volume on MRI at 30 days. Secondary endpoints included infarct volume according to the site (proximal/distal) of arterial occlusion and recanalization after thrombolysis. RESULTS:From October 2009 to July 2013, 127 patients were enrolled. The primary endpoint was assessed in 110 of 127 patients. The reduction of infarct volume in the cyclosporine compared with the control group was overall not significant (21.8 mL [interquartile range, IQR 5.1, 69.2 mL] vs 28.8 mL [IQR 7.7, 95.0 mL], respectively; p = 0.18). However, in patients with proximal occlusion and effective recanalization, infarct volume was significantly reduced in the cyclosporine compared with the control group (14.9 mL [IQR 1.3, 23.2 mL] vs 48.3 mL [IQR 34.5, 118.2 mL], respectively; p = 0.009). CONCLUSIONS:Cyclosporine was generally not effective in reducing infarct size. However, a smaller infarct size was observed in patients with proximal cerebral artery occlusion and efficient recanalization. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that in patients with an acute anterior-circulation stroke, thrombolysis plus IV cyclosporine does not significantly decrease 30-day MRI infarct volume compared with thrombolysis alone.
RCT Entities:
OBJECTIVES: We examined whether IV administration of cyclosporine in combination with thrombolysis might reduce cerebral infarct size. METHODS:Patients aged 18 to 85 years, presenting with an anterior-circulation stroke and eligible for thrombolytic therapy, were enrolled in this multicenter, single-blinded, controlled trial. Fifteen minutes after randomization, patients received either an IV bolus injection of 2.0 mg/kg cyclosporine (Sandimmune, Novartis) or placebo. The primary endpoint was infarct volume on MRI at 30 days. Secondary endpoints included infarct volume according to the site (proximal/distal) of arterial occlusion and recanalization after thrombolysis. RESULTS: From October 2009 to July 2013, 127 patients were enrolled. The primary endpoint was assessed in 110 of 127 patients. The reduction of infarct volume in the cyclosporine compared with the control group was overall not significant (21.8 mL [interquartile range, IQR 5.1, 69.2 mL] vs 28.8 mL [IQR 7.7, 95.0 mL], respectively; p = 0.18). However, in patients with proximal occlusion and effective recanalization, infarct volume was significantly reduced in the cyclosporine compared with the control group (14.9 mL [IQR 1.3, 23.2 mL] vs 48.3 mL [IQR 34.5, 118.2 mL], respectively; p = 0.009). CONCLUSIONS:Cyclosporine was generally not effective in reducing infarct size. However, a smaller infarct size was observed in patients with proximal cerebral artery occlusion and efficient recanalization. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that in patients with an acute anterior-circulation stroke, thrombolysis plus IVcyclosporine does not significantly decrease 30-day MRI infarct volume compared with thrombolysis alone.
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