{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:23:47Z","timestamp":1791901427945,"version":"4.3.4"},"reference-count":13,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:sec>\n            <jats:title>Background and Purpose\u2014<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods\u2014<\/jats:title>\n            <jats:p>Ischemic stroke patients with occlusion\/high-grade stenosis in major cerebral arteries were randomly assigned to intravenous treatment with desmoteplase (90 \u03bcg\/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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results\u2014<\/jats:title>\n            <jats:p>\n              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;\n              <jats:italic>P<\/jats:italic>\n              =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;\n              <jats:italic>P<\/jats:italic>\n              =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\u20132.35;\n              <jats:italic>P<\/jats:italic>\n              =0.019). Recanalization was associated with favorable outcomes (mRS 0\u20132) at day 90 in both the treatment arms.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Late treatment with intravenous 90 \u00b5g\/kg desmoteplase is safe, increases arterial recanalization, but does not significantly improve functional outcome at 3 months.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Clinical Trial Registration\u2014<\/jats:title>\n            <jats:p>\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.clinicaltrials.gov\">http:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              . Unique identifier: NCT00856661.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.116.013715","type":"journal-article","created":{"date-parts":[[2016,11,2]],"date-time":"2016-11-02T01:08:37Z","timestamp":1478048917000},"page":"2880-2887","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":58,"title":["Desmoteplase 3 to 9 Hours After Major Artery Occlusion Stroke"],"prefix":"10.1161","volume":"47","author":[{"suffix":"Prof Dr me","given":"R\u00fcdiger","family":"von Kummer","sequence":"first","affiliation":[{"name":"From the Universit\u00e4tsklinikum Carl Gustav Carus an der Technischen Universit\u00e4t, 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, Charit\u00e9-Universit\u00e4tsmedizin 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.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etsuro","family":"Mori","sequence":"additional","affiliation":[{"name":"From the Universit\u00e4tsklinikum Carl Gustav Carus an der Technischen Universit\u00e4t, 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, Charit\u00e9-Universit\u00e4tsmedizin 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.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Truelsen","sequence":"additional","affiliation":[{"name":"From the Universit\u00e4tsklinikum Carl Gustav Carus an der Technischen Universit\u00e4t, 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, Charit\u00e9-Universit\u00e4tsmedizin 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.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens-Kristian S.","family":"Jensen","sequence":"additional","affiliation":[{"name":"From the Universit\u00e4tsklinikum Carl Gustav Carus an der Technischen Universit\u00e4t, 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, Charit\u00e9-Universit\u00e4tsmedizin 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.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f8rn A.","family":"Gr\u00f8nning","sequence":"additional","affiliation":[{"name":"From the Universit\u00e4tsklinikum Carl Gustav Carus an der Technischen Universit\u00e4t, 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, Charit\u00e9-Universit\u00e4tsmedizin 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.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Prof Dr me","given":"Jochen B.","family":"Fiebach","sequence":"additional","affiliation":[{"name":"From the Universit\u00e4tsklinikum Carl Gustav Carus an der Technischen Universit\u00e4t, 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, Charit\u00e9-Universit\u00e4tsmedizin 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.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Prof Dr me","given":"Karl-Olof","family":"Lovblad","sequence":"additional","affiliation":[{"name":"From the Universit\u00e4tsklinikum Carl Gustav Carus an der Technischen Universit\u00e4t, 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, Charit\u00e9-Universit\u00e4tsmedizin 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.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvador","family":"Pedraza","sequence":"additional","affiliation":[{"name":"From the Universit\u00e4tsklinikum Carl Gustav Carus an der Technischen Universit\u00e4t, 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, Charit\u00e9-Universit\u00e4tsmedizin 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.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier M.","family":"Romero","sequence":"additional","affiliation":[{"name":"From the Universit\u00e4tsklinikum Carl Gustav Carus an der Technischen Universit\u00e4t, 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, Charit\u00e9-Universit\u00e4tsmedizin 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.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugues","family":"Chabriat","sequence":"additional","affiliation":[{"name":"From the Universit\u00e4tsklinikum Carl Gustav Carus an der Technischen Universit\u00e4t, 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, Charit\u00e9-Universit\u00e4tsmedizin 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.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ku-Chou","family":"Chang","sequence":"additional","affiliation":[{"name":"From the Universit\u00e4tsklinikum Carl Gustav Carus an der Technischen Universit\u00e4t, 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, Charit\u00e9-Universit\u00e4tsmedizin 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.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoni","family":"D\u00e1valos","sequence":"additional","affiliation":[{"name":"From the Universit\u00e4tsklinikum Carl Gustav Carus an der Technischen Universit\u00e4t, 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, Charit\u00e9-Universit\u00e4tsmedizin 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.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary A.","family":"Ford","sequence":"additional","affiliation":[{"name":"From the Universit\u00e4tsklinikum Carl Gustav Carus an der Technischen Universit\u00e4t, 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, Charit\u00e9-Universit\u00e4tsmedizin 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.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Grotta","sequence":"additional","affiliation":[{"name":"From the Universit\u00e4tsklinikum Carl Gustav Carus an der Technischen Universit\u00e4t, 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, Charit\u00e9-Universit\u00e4tsmedizin 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.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markku","family":"Kaste","sequence":"additional","affiliation":[{"name":"From the Universit\u00e4tsklinikum Carl Gustav Carus an der Technischen Universit\u00e4t, 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, Charit\u00e9-Universit\u00e4tsmedizin 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.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee H.","family":"Schwamm","sequence":"additional","affiliation":[{"name":"From the Universit\u00e4tsklinikum Carl Gustav Carus an der Technischen Universit\u00e4t, 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, Charit\u00e9-Universit\u00e4tsmedizin 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.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashfaq","family":"Shuaib","sequence":"additional","affiliation":[{"name":"From the Universit\u00e4tsklinikum Carl Gustav Carus an der Technischen Universit\u00e4t, 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, Charit\u00e9-Universit\u00e4tsmedizin 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.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory W.","family":"Albers","sequence":"additional","affiliation":[{"name":"From the Universit\u00e4tsklinikum Carl Gustav Carus an der Technischen Universit\u00e4t, 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, Charit\u00e9-Universit\u00e4tsmedizin 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.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60584-5"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000149938.08731.2c"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000217403.66996.6d"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(08)70267-9"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.111.642322"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(15)00047-2"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.115.009917"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1747-4949.2012.00910.x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1411587"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1414792"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1414905"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1503780"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1415061"}],"container-title":["Stroke"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/STROKEAHA.116.013715","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T14:00:29Z","timestamp":1715608829000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/STROKEAHA.116.013715"}},"subtitle":["The DIAS-4 Trial (Efficacy and Safety Study of Desmoteplase to Treat Acute Ischemic Stroke)"],"short-title":[],"issued":{"date-parts":[[2016,12]]},"references-count":13,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2016,12]]}},"alternative-id":["10.1161\/STROKEAHA.116.013715"],"URL":"https:\/\/doi.org\/10.1161\/strokeaha.116.013715","relation":{},"ISSN":["0039-2499","1524-4628"],"issn-type":[{"value":"0039-2499","type":"print"},{"value":"1524-4628","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12]]},"assertion":[{"value":"2016-04-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-08-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-11-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}