Desmoteplase 3 to 9 Hours after Major Artery Occlusion Stroke

Rüdiger Von Kummer, Etsuro Mori, Thomas Truelsen, Jens Kristian S. Jensen, Bjørn A. Grønning, Jochen B. Fiebach, Karl Olof Lovblad, Salvador Pedraza, Javier M. Romero, Hugues Chabriat, Ku Chou Chang, Antoni Dávalos, Gary A. Ford, James Grotta, Markku Kaste, Lee H. Schwamm, Ashfaq Shuaib, Gregory W. Albers

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2880-2887
Number of pages8
JournalStroke
Volume47
Issue number12
DOIs
Publication statusPublished - 2016 Dec 1

Keywords

  • brain ischemia
  • cerebral arteries
  • goals
  • intracranial hemorrhage
  • stroke

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialised Nursing

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