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Title: MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset.
Austin Authors: Thomalla, Götz;Simonsen, Claus Z;Boutitie, Florent;Andersen, Grethe;Berthezene, Yves;Cheng, Bastian;Cheripelli, Bharath;Cho, Tae-Hee;Fazekas, Franz;Fiehler, Jens;Ford, Ian;Galinovic, Ivana;Gellissen, Susanne;Golsari, Amir;Gregori, Johannes;Günther, Matthias;Guibernau, Jorge;Häusler, Karl Georg;Hennerici, Michael;Kemmling, André;Marstrand, Jacob;Modrau, Boris;Neeb, Lars;Perez de la Ossa, Natalia;Puig, Josep;Ringleb, Peter;Roy, Pascal;Scheel, Enno;Schonewille, Wouter;Serena, Joaquin;Sunaert, Stefan;Villringer, Kersten;Wouters, Anke;Thijs, Vincent N ;Ebinger, Martin;Endres, Matthias;Fiebach, Jochen B;Lemmens, Robin;Muir, Keith W;Nighoghossian, Norbert;Pedraza, Salvador;Gerloff, Christian
Affiliation: Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf, Germany
Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Germany
ZytoService Deutschland (E.S.), Hamburg, Universitätsklinik für Neurologie, Medizinische Universität Graz, Graz, Germany
Centrum für Schlaganfallforschung Berlin, Germany
Klinik und Hochschulambulanz für Neurologie, Germany
Charité-Universitätsmedizin Berlin, Germany
Neurologie der Rehaklinik Medical Park Humboldtmühle, Germany
Berlin, Mediri, Germany
Department of Neurology, Medical Faculty Mannheim, University of Heidelberg, Germany
Neurologische Klinik, Universitätsklinikum Heidelberg, Germany
Heidelberg, Fraunhofer MEVIS and University of Bremen, Bremen, Germany
Institut für Neuroradiologie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
Department of Neurology, Aarhus University Hospital, Aarhus, Denmark
Department of Neurology, Bispebjerg Hospital, Copenhagen University Hospital, Copenhagen, Denmark
Department of Neurology, Stroke Unit, Aalborg University Hospital, Aalborg, Denmark
Hospices Civils de Lyon, Service de Biostatistique, France
Neuroradiology Department, Neurological Hospital, University Lyon, France
Department of Stroke Medicine, Université Claude Bernard Lyon 1, France
Hospices Civils de Lyon, Lyon, France
Université Lyon 1 and Centre National de la Recherche Scientifique, UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, Villeurbanne, France
Institute of Neuroscience and Psychology and the Robertson Centre for Biostatistics, University of Glasgow, Glasgow, United Kingdom
Fundació Salut Empordà Hospital, Figueres, Spain
Stroke Unit, Department of Neurosciences, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain
Department of Radiology and the Stroke Unit, Hospital Universitari Doctor Josep Trueta, Institut d'Investigació Biomèdica de Girona, Girona, Spain
Department of Neurology, St. Antonius Hospital, Nieuwegein, Netherlands
University Medical Center Utrecht, Utrecht, Netherlands
Department of Imaging and Pathology, University of Leuven, Belgium
Department of Neurology, University Hospitals Leuven, Belgium
KU Leuven-University of Leuven, Department of Neurosciences, Experimental Neurology, and the VIB-KU Leuven Center for Brain and Disease Research, Laboratory of Neurobiology, Leuven, Belgium
The Florey Institute of Neuroscience and Mental Health, Heidelberg, Victoria, Australia
Issue Date: 16-Aug-2018 2018-05-16
Publication information: The New England Journal of Medicine 2018; 379(7): 611-622
Abstract: Background Under current guidelines, intravenous thrombolysis is used to treat acute stroke only if it can be ascertained that the time since the onset of symptoms was less than 4.5 hours. We sought to determine whether patients with stroke with an unknown time of onset and features suggesting recent cerebral infarction on magnetic resonance imaging (MRI) would benefit from thrombolysis with the use of intravenous alteplase. Methods In a multicenter trial, we randomly assigned patients who had an unknown time of onset of stroke to receive either intravenous alteplase or placebo. All the patients had an ischemic lesion that was visible on MRI diffusion-weighted imaging but no parenchymal hyperintensity on fluid-attenuated inversion recovery (FLAIR), which indicated that the stroke had occurred approximately within the previous 4.5 hours. We excluded patients for whom thrombectomy was planned. The primary end point was favorable outcome, as defined by a score of 0 or 1 on the modified Rankin scale of neurologic disability (which ranges from 0 [no symptoms] to 6 [death]) at 90 days. A secondary outcome was the likelihood that alteplase would lead to lower ordinal scores on the modified Rankin scale than would placebo (shift analysis). Results The trial was stopped early owing to cessation of funding after the enrollment of 503 of an anticipated 800 patients. Of these patients, 254 were randomly assigned to receive alteplase and 249 to receive placebo. A favorable outcome at 90 days was reported in 131 of 246 patients (53.3%) in the alteplase group and in 102 of 244 patients (41.8%) in the placebo group (adjusted odds ratio, 1.61; 95% confidence interval [CI], 1.09 to 2.36; P=0.02). The median score on the modified Rankin scale at 90 days was 1 in the alteplase group and 2 in the placebo group (adjusted common odds ratio, 1.62; 95% CI, 1.17 to 2.23; P=0.003). There were 10 deaths (4.1%) in the alteplase group and 3 (1.2%) in the placebo group (odds ratio, 3.38; 95% CI, 0.92 to 12.52; P=0.07). The rate of symptomatic intracranial hemorrhage was 2.0% in the alteplase group and 0.4% in the placebo group (odds ratio, 4.95; 95% CI, 0.57 to 42.87; P=0.15). Conclusions In patients with acute stroke with an unknown time of onset, intravenous alteplase guided by a mismatch between diffusion-weighted imaging and FLAIR in the region of ischemia resulted in a significantly better functional outcome and numerically more intracranial hemorrhages than placebo at 90 days. (Funded by the European Union Seventh Framework Program; WAKE-UP number, NCT01525290; and EudraCT number, 2011-005906-32 .).
DOI: 10.1056/NEJMoa1804355
ORCID: 0000-0002-4785-1449
PubMed URL: 29766770
Type: Journal Article
Appears in Collections:Journal articles

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