A Randomized Trial of Intravenous Alteplase before Endovascular Treatment for Stroke

MR CLEAN–NO IV Investigators, 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, Diederik W J Dippel, Aad van der Lugt, Adriaan C G M van Es, Jelis Boiten, Geert J Lycklama À Nijeholt, Koos Keizer, Rob A R Gons, Lonneke S F Yo, Robert J van Oostenbrugge, Wim H van ZwamBob Roozenbeek, H Bart van der Worp, Rob T H Lo, 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, Reinoud P H Bokkers, Julia H van Tuijl, Hans Kortman, Floris H B M Schreuder, Hieronymus D Boogaarts, Karlijn F de Laat, Lukas C van Dijk, Heleen M den Hertog, Boudewijn A A M van Hasselt, Paul J A M Brouwers, Tomas Bulut, Michel J M Remmers, Anouk van Norden, Farshad Imani, Anouk D Rozeman, Otto E H Elgersma, Philippe Desfontaines, Denis Brisbois, Yves Samson, Frédéric Clarençon, Menno Krietemeijer, Alida A. Postma, Pieter-Jan van Doormaal, René van den Berg, Anouk van der Hoorn, Ludo F.M. Beenen, Daan Nieboer, Hester F. Lingsma, Bart J. Emmer, Jonathan M. Coutinho, Charles B.L.M. Majoie, Yvo B.W.E.M. Roos

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Abstract

BACKGROUND: The value of administering intravenous alteplase before endovascular treatment (EVT) for acute ischemic stroke has not been studied extensively, particularly in non-Asian populations.

METHODS: We 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.

RESULTS: The 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).

CONCLUSIONS: In 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.).

Original languageEnglish
Pages (from-to)1833-1844
Number of pages12
JournalNew England Journal of Medicine
Volume385
Issue number20
DOIs
Publication statusPublished - 11-Nov-2021

Keywords

  • ACUTE ISCHEMIC-STROKE
  • MECHANICAL THROMBECTOMY
  • THROMBOLYSIS
  • GUIDELINES
  • THERAPY
  • CARE

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