• Natalie E LeCouffe, Manon Kappelhof, Kilian M Treurniet, Leon A Rinkel, Agnetha E Bruggeman, Olvert A Berkhemer, Lennard Wolff, Henk van Voorst, Manon L Tolhuisen, DippelDiederik W JDWJFrom the Departments of Neurology (N.E.L., L.A.R., J.M.C., Y.B.W.E.M.R.), Radiology and Nuclear Medicine (M.K., K.M.T., A.E.B., O.A.B., H.V., M.L.T., R.B., L.F.M.B., B.J.E., C.B.L.M.M.), and Biomedical Engineering and Physics (O.A.B.,, Aad van der Lugt, Adriaan C G M van Es, Jelis Boiten, Lycklama À NijeholtGeert JGJFrom the Departments of Neurology (N.E.L., L.A.R., J.M.C., Y.B.W.E.M.R.), Radiology and Nuclear Medicine (M.K., K.M.T., A.E.B., O.A.B., H.V., M.L.T., R.B., L.F.M.B., B.J.E., C.B.L.M.M.), and Biomedical Engineering and Physics (, Koos Keizer, GonsRob A RRARFrom the Departments of Neurology (N.E.L., L.A.R., J.M.C., Y.B.W.E.M.R.), Radiology and Nuclear Medicine (M.K., K.M.T., A.E.B., O.A.B., H.V., M.L.T., R.B., L.F.M.B., B.J.E., C.B.L.M.M.), and Biomedical Engineering and Physics (O.A.B., H.V., , Lonneke S F Yo, Robert J van Oostenbrugge, Wim H van Zwam, Bob Roozenbeek, H Bart van der Worp, LoRob T HRTHFrom the Departments of Neurology (N.E.L., L.A.R., J.M.C., Y.B.W.E.M.R.), Radiology and Nuclear Medicine (M.K., K.M.T., A.E.B., O.A.B., H.V., M.L.T., R.B., L.F.M.B., B.J.E., C.B.L.M.M.), and Biomedical Engineering and Physics (O.A.B., H.V., M., Ido R van den Wijngaard, Inger R de Ridder, Vincent Costalat, Caroline Arquizan, Robin Lemmens, Jelle Demeestere, Jeannette Hofmeijer, Jasper M Martens, Wouter J Schonewille, Jan-Albert Vos, Maarten Uyttenboogaart, BokkersReinoud P HRPHFrom the Departments of Neurology (N.E.L., L.A.R., J.M.C., Y.B.W.E.M.R.), Radiology and Nuclear Medicine (M.K., K.M.T., A.E.B., O.A.B., H.V., M.L.T., R.B., L.F.M.B., B.J.E., C.B.L.M.M.), and Biomedical Engineering and Physics (O.A.B.,, Julia H van Tuijl, Hans Kortman, SchreuderFloris H B MFHBMFrom the Departments of Neurology (N.E.L., L.A.R., J.M.C., Y.B.W.E.M.R.), Radiology and Nuclear Medicine (M.K., K.M.T., A.E.B., O.A.B., H.V., M.L.T., R.B., L.F.M.B., B.J.E., C.B.L.M.M.), and Biomedical Engineering and Physics (O.A, Hieronymus D Boogaarts, Karlijn F de Laat, Lukas C van Dijk, Heleen M den Hertog, van HasseltBoudewijn A A MBAAMFrom the Departments of Neurology (N.E.L., L.A.R., J.M.C., Y.B.W.E.M.R.), Radiology and Nuclear Medicine (M.K., K.M.T., A.E.B., O.A.B., H.V., M.L.T., R.B., L.F.M.B., B.J.E., C.B.L.M.M.), and Biomedical Engineering and Physics, BrouwersPaul J A MPJAMFrom the Departments of Neurology (N.E.L., L.A.R., J.M.C., Y.B.W.E.M.R.), Radiology and Nuclear Medicine (M.K., K.M.T., A.E.B., O.A.B., H.V., M.L.T., R.B., L.F.M.B., B.J.E., C.B.L.M.M.), and Biomedical Engineering and Physics (O.A.B., Tomas Bulut, RemmersMichel J MMJMFrom the Departments of Neurology (N.E.L., L.A.R., J.M.C., Y.B.W.E.M.R.), Radiology and Nuclear Medicine (M.K., K.M.T., A.E.B., O.A.B., H.V., M.L.T., R.B., L.F.M.B., B.J.E., C.B.L.M.M.), and Biomedical Engineering and Physics (O.A.B., , Anouk van Norden, Farshad Imani, Anouk D Rozeman, ElgersmaOtto E HOEHFrom the Departments of Neurology (N.E.L., L.A.R., J.M.C., Y.B.W.E.M.R.), Radiology and Nuclear Medicine (M.K., K.M.T., A.E.B., O.A.B., H.V., M.L.T., R.B., L.F.M.B., B.J.E., C.B.L.M.M.), and Biomedical Engineering and Physics (O.A.B., H, Philippe Desfontaines, Denis Brisbois, Yves Samson, Frédéric Clarençon, G Menno Krietemeijer, Alida A Postma, Pieter-Jan van Doormaal, René van den Berg, Anouk van der Hoorn, BeenenLudo F MLFM0000-0001-9204-1026From the Departments of Neurology (N.E.L., L.A.R., J.M.C., Y.B.W.E.M.R.), Radiology and Nuclear Medicine (M.K., K.M.T., A.E.B., O.A.B., H.V., M.L.T., R.B., L.F.M.B., B.J.E., C.B.L.M.M.), and Biomedical Engineering and P, Daan Nieboer, Hester F Lingsma, Bart J Emmer, Jonathan M Coutinho, MajoieCharles B L MCBLMFrom the Departments of Neurology (N.E.L., L.A.R., J.M.C., Y.B.W.E.M.R.), Radiology and Nuclear Medicine (M.K., K.M.T., A.E.B., O.A.B., H.V., M.L.T., R.B., L.F.M.B., B.J.E., C.B.L.M.M.), and Biomedical Engineering and Physics (O.A.B, RoosYvo B W E MYBWEMFrom the Departments of Neurology (N.E.L., L.A.R., J.M.C., Y.B.W.E.M.R.), Radiology and Nuclear Medicine (M.K., K.M.T., A.E.B., O.A.B., H.V., M.L.T., R.B., L.F.M.B., B.J.E., C.B.L.M.M.), and Biomedical Engineering and Physics (O.A.B., , and MR CLEAN–NO IV Investigators.
• From the Departments of Neurology (N.E.L., L.A.R., J.M.C., Y.B.W.E.M.R.), Radiology and Nuclear Medicine (M.K., K.M.T., A.E.B., O.A.B., H.V., M.L.T., R.B., L.F.M.B., B.J.E., C.B.L.M.M.), and Biomedical Engineering and Physics (O.A.B., H.V., M.L.T.), Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience, Amsterdam, the Departments of Radiology (K.M.T., G.J.L.N., I.R.W.) and Neurology (J.B., I.R.W.), The Hague Medical Center, and the Departments of Neurology (K.F.L.) and Radiology (L.C.D.), Haga Hospital, The Hague, the Departments of Radiology and Nuclear Medicine (O.A.B., L.W., A.L., P.-J.D.), Neurology (D.W.J.D., B.R.), and Public Health (D.N., H.F.L.), Erasmus MC University Medical Center, Rotterdam, the Department of Radiology, Leiden University Medical Center, Leiden (A.C.G.M.E.), the Departments of Neurology (K.K., R.A.R.G.) and Radiology (L.S.F.Y., G.M.K.), Catharina Hospital, Eindhoven, the Department of Neurology, Cardiovascular Research Institute Maastricht (R.J.O., I.R.R.), and the Department of Radiology and Nuclear Medicine (W.H.Z., A.A.P.), Maastricht University Medical Center, and the School for Mental Health and Sciences, Maastricht University (A.A.P.), Maastricht, the Department of Neurology and Neurosurgery, Brain Center (H.B.W.), and the Department of Radiology (R.T.H.L.), University Medical Center Utrecht, Utrecht, the Departments of Neurology (J.H.) and Radiology (J.M.M.), Rijnstate Hospital, Arnhem, the Departments of Neurology (W.J.S.) and Radiology (J.-A.V.), Sint Antonius Hospital, Nieuwegein, the Departments of Neurology (M.U.) and Radiology, Medical Imaging Center (R.P.H.B., A.H.), University Medical Center Groningen, Groningen, the Departments of Neurology (J.H.T.) and Radiology (H.K.), Elisabeth-TweeSteden Hospital, Tilburg, Radboud University Medical Center, Donders Institute for Brain, Cognition, and Behavior, Department of Neurology (F.H.B.M.S.), and the Department of Neurosurgery, Radboud University Medical Center (H.D.B.), Nijmegen, the Departments of Neurology (H.M.H.) and Radiology and Nuclear Medicine (B.A.A.M.H.), Isala Hospital, Zwolle, the Departments of Neurology (P.J.A.M.B.) and Radiology (T.B.), Medisch Spectrum Twente, Enschede, the Departments of Neurology (M.J.M.R., A.N.) and Radiology (F.I.), Amphia Hospital, Breda, and the Departments of Neurology (A.D.R.) and Radiology (O.E.H.E.), Albert Schweitzer Hospital, Dordrecht - all in the Netherlands; the Departments of Neuroradiology (V.C.) and Neurology (C.A.), Centre Hospitalier Universitaire de Montpellier, Montpellier, and the Departments of Neurology (Y.S.) and Neuroradiology (F.C.), Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris Sorbonne Université, Paris - both in France; and the Department of Neurosciences, KU Leuven-University of Leuven, Experimental Neurology (R.L., J.D.), Vlaams Instituut voor Biotechnologie Center for Brain and Disease Research (R.L., J.D.), and University Hospitals Leuven, Department of Neurology (R.L., J.D.), Leuven, and the Departments of Neurology (P.D.) and Radiology (D.B.), Centre Hospitalier Chrétien, Liege - all in Belgium.
• N. Engl. J. Med. 2021 Nov 11; 385 (20): 1833-1844.

BackgroundThe value of administering intravenous alteplase before endovascular treatment (EVT) for acute ischemic stroke has not been studied extensively, particularly in non-Asian populations.MethodsWe performed an open-label, multicenter, randomized trial in Europe involving patients with stroke who presented directly to a hospital that was capable of providing EVT and who were eligible for intravenous alteplase and EVT. Patients were randomly assigned in a 1:1 ratio to receive EVT alone or intravenous alteplase followed by EVT (the standard of care). The primary end point was functional outcome on the modified Rankin scale (range, 0 [no disability] to 6 [death]) at 90 days. We assessed the superiority of EVT alone over alteplase plus EVT, as well as noninferiority by a margin of 0.8 for the lower boundary of the 95% confidence interval for the odds ratio of the two trial groups. Death from any cause and symptomatic intracerebral hemorrhage were the main safety end points.ResultsThe analysis included 539 patients. The median score on the modified Rankin scale at 90 days was 3 (interquartile range, 2 to 5) with EVT alone and 2 (interquartile range, 2 to 5) with alteplase plus EVT. The adjusted common odds ratio was 0.84 (95% confidence interval [CI], 0.62 to 1.15; P = 0.28), which showed neither superiority nor noninferiority of EVT alone. Mortality was 20.5% with EVT alone and 15.8% with alteplase plus EVT (adjusted odds ratio, 1.39; 95% CI, 0.84 to 2.30). Symptomatic intracerebral hemorrhage occurred in 5.9% and 5.3% of the patients in the respective groups (adjusted odds ratio, 1.30; 95% CI, 0.60 to 2.81).ConclusionsIn a randomized trial involving European patients, EVT alone was neither superior nor noninferior to intravenous alteplase followed by EVT with regard to disability outcome at 90 days after stroke. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups. (Funded by the Collaboration for New Treatments of Acute Stroke consortium and others; MR CLEAN-NO IV ISRCTN number, ISRCTN80619088.).Copyright © 2021 Massachusetts Medical Society.

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