Rüdiger von Kummer1, Etsuro Mori2, Thomas Truelsen2, Jens-Kristian S Jensen2, Bjørn A Grønning2, Jochen B Fiebach2, Karl-Olof Lovblad2, Salvador Pedraza2, Javier M Romero2, Hugues Chabriat2, Ku-Chou Chang2, Antoni Dávalos2, Gary A Ford2, James Grotta2, Markku Kaste2, Lee H Schwamm2, Ashfaq Shuaib2, Gregory W Albers2. 1. From the Universitätsklinikum Carl Gustav Carus an der Technischen Universität, Dresden, Germany (R.v.K.); Tohoku University Graduate School of Medicine, Sendai, Japan (E.M.); H. Lundbeck A/S, Valby, Denmark (T.T., J.-K.S.J., B.A.G.); Center for Stroke Research Berlin, Charité-Universitätsmedizin Berlin, Germany (J.B.F.); University of Geneva, Switzerland (K.-O.L.); c IDIBGI. Hospital Dr Josep Trueta, UDG. Girona, Spain (S.P.); Department of Radiology, Harvard Medical School, Boston, MA (J.M.R.); Department of Neurology, Hopital Lariboisiere APHP, University Denis Diderot and INSERM U1161, DHU NeuroVasc, Paris, France (H.C.); Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, Taiwan (K.-C.C.); Department of Neurosciences Hospital Germans Trias i Pujol, Universitat Autonoma, Barcelona, Spain (A.D.); Oxford University Hospitals and Medical Sciences Division, University of Oxford, United Kingdom (G.A.F.); Memorial Hermann Hospital, Houston, TX (J.G.); Department of Neurology, Helsinki University Hospital, Clinical Neurosciences, Neurology, University of Helsinki, Finland (M.K.); Department of Neurology and Stroke Service, Massachusetts General Hospital, Harvard Medical School, Boston (L.H.S.); University of Alberta, Edmonton, Canada (A.S.); and Stanford University Medical Center, Palo Alto, CA (G.W.A.). ruediger.vonkummer@uniklinikum-dresden.de. 2. From the Universitätsklinikum Carl Gustav Carus an der Technischen Universität, Dresden, Germany (R.v.K.); Tohoku University Graduate School of Medicine, Sendai, Japan (E.M.); H. Lundbeck A/S, Valby, Denmark (T.T., J.-K.S.J., B.A.G.); Center for Stroke Research Berlin, Charité-Universitätsmedizin Berlin, Germany (J.B.F.); University of Geneva, Switzerland (K.-O.L.); c IDIBGI. Hospital Dr Josep Trueta, UDG. Girona, Spain (S.P.); Department of Radiology, Harvard Medical School, Boston, MA (J.M.R.); Department of Neurology, Hopital Lariboisiere APHP, University Denis Diderot and INSERM U1161, DHU NeuroVasc, Paris, France (H.C.); Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, Taiwan (K.-C.C.); Department of Neurosciences Hospital Germans Trias i Pujol, Universitat Autonoma, Barcelona, Spain (A.D.); Oxford University Hospitals and Medical Sciences Division, University of Oxford, United Kingdom (G.A.F.); Memorial Hermann Hospital, Houston, TX (J.G.); Department of Neurology, Helsinki University Hospital, Clinical Neurosciences, Neurology, University of Helsinki, Finland (M.K.); Department of Neurology and Stroke Service, Massachusetts General Hospital, Harvard Medical School, Boston (L.H.S.); University of Alberta, Edmonton, Canada (A.S.); and Stanford University Medical Center, Palo Alto, CA (G.W.A.).
Abstract
BACKGROUND AND PURPOSE: The DIAS-3 trial (Efficacy and Safety Study of Desmoteplase to Treat Acute Ischemic Stroke [phase 3]) did not demonstrate a significant clinical benefit of desmoteplase administered 3 to 9 hours after stroke in patients with major artery occlusion. We present the results of the prematurely terminated DIAS-4 trial together with a post hoc pooled analysis of the concomitant DIAS-3, DIAS-4, and DIAS-J (Japan) trials to better understand the potential risks and benefits of intravenous desmoteplase for the treatment of ischemic stroke in an extended time window. METHODS:Ischemic stroke patients with occlusion/high-grade stenosis in major cerebral arteries were randomly assigned to intravenous treatment with desmoteplase (90 μg/kg) or placebo. The primary outcome was modified Rankin Scale (mRS) score of 0 to 2 at day 90. Safety assessments included mortality, symptomatic intracranial hemorrhage, and other serious adverse events. RESULTS: In DIAS-4, 52 of 124 (41.9%) desmoteplase-treated and 46 of 128 (35.9%) placebo-treated patients achieved an mRS score of 0 to 2 (odds ratio, 1.45; 95% confidence interval, 0.79; 2.64; P=0.23) with equal mortality, frequency of symptomatic intracranial hemorrhage, and other serious adverse events in both the treatment arms. In the pooled analysis, mRS score of 0 to 2 was achieved by 184 of 376 (48.9%) desmoteplase-treated versus 171 of 381 (44.9%) placebo-treated patients (odds ratio, 1.33; 95% confidence interval, 0.95; 1.85; P=0.096). Treatment with desmoteplase was safe and increased the recanalization rate (107/217 [49.3%] versus 85/222 [38.3%]; odds ratio, 1.59; 95% confidence interval, 1.08-2.35; P=0.019). Recanalization was associated with favorable outcomes (mRS 0-2) at day 90 in both the treatment arms. CONCLUSIONS: Late treatment with intravenous 90 µg/kg desmoteplase is safe, increases arterial recanalization, but does not significantly improve functional outcome at 3 months. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00856661.
RCT Entities:
BACKGROUND AND PURPOSE: The DIAS-3 trial (Efficacy and Safety Study of Desmoteplase to Treat Acute Ischemic Stroke [phase 3]) did not demonstrate a significant clinical benefit of desmoteplase administered 3 to 9 hours after stroke in patients with major artery occlusion. We present the results of the prematurely terminated DIAS-4 trial together with a post hoc pooled analysis of the concomitant DIAS-3, DIAS-4, and DIAS-J (Japan) trials to better understand the potential risks and benefits of intravenous desmoteplase for the treatment of ischemic stroke in an extended time window. METHODS:Ischemic strokepatients with occlusion/high-grade stenosis in major cerebral arteries were randomly assigned to intravenous treatment with desmoteplase (90 μg/kg) or placebo. The primary outcome was modified Rankin Scale (mRS) score of 0 to 2 at day 90. Safety assessments included mortality, symptomatic intracranial hemorrhage, and other serious adverse events. RESULTS: In DIAS-4, 52 of 124 (41.9%) desmoteplase-treated and 46 of 128 (35.9%) placebo-treated patients achieved an mRS score of 0 to 2 (odds ratio, 1.45; 95% confidence interval, 0.79; 2.64; P=0.23) with equal mortality, frequency of symptomatic intracranial hemorrhage, and other serious adverse events in both the treatment arms. In the pooled analysis, mRS score of 0 to 2 was achieved by 184 of 376 (48.9%) desmoteplase-treated versus 171 of 381 (44.9%) placebo-treated patients (odds ratio, 1.33; 95% confidence interval, 0.95; 1.85; P=0.096). Treatment with desmoteplase was safe and increased the recanalization rate (107/217 [49.3%] versus 85/222 [38.3%]; odds ratio, 1.59; 95% confidence interval, 1.08-2.35; P=0.019). Recanalization was associated with favorable outcomes (mRS 0-2) at day 90 in both the treatment arms. CONCLUSIONS: Late treatment with intravenous 90 µg/kg desmoteplase is safe, increases arterial recanalization, but does not significantly improve functional outcome at 3 months. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00856661.
Authors: Jose Fernandez-Ferro; Lee H Schwamm; Miguel A Descalzo; Rachael MacIsaac; Patrick D Lyden; Kennedy R Lees Journal: Eur Stroke J Date: 2020-02-06
Authors: Paula Muñoz Venturelli; Jason P Appleton; Craig S Anderson; Philip M Bath Journal: Curr Neurol Neurosci Rep Date: 2018-09-18 Impact factor: 5.081