Stroke. 2005;36:66-73
Published online before print November 29, 2004, doi: 10.1161/01.STR.0000149938.08731.2c
Published online before print November 29, 2004, doi: 10.1161/01.STR.0000149938.08731.2c
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(Stroke. 2005;36:66.)
© 2005 American Heart Association, Inc.
Original Contributions |
The Desmoteplase in Acute Ischemic Stroke Trial (DIAS)
A Phase II MRI-Based 9-Hour Window Acute Stroke Thrombolysis Trial With Intravenous Desmoteplase
From the Department of Neurology (W.H.), University of Heidelberg, Heidelberg; PAION GmbH (Y.A.-R., M.S.), Aachen; ClinResearch GmbH (M.F.), Köln, Germany; Centre Hospitalier Universitaire Vaudois (J.B.), Department of Neurology, Lausanne, Switzerland; Hospital Universitari Dr Josep Trueta (A.D.), Girona, Spain; the University of Calgary (M.E.), Heritage Medical Research Building. Calgary, Alberta, Canada; Helsinki University Central Hospital (M.K.), Department of Clinical Neurosciences, Helsinki, Finland; Western Infirmary (K.R.L.), University Department, of Medicine & Therapeutics, Glasgow, United Kingdom; the Stanford Stroke Center (G.A), Palo Alto, Calif; the Cleveland Clinic Foundation (A.F.), Department of Neurology, Cleveland, Ohio; and the National Institute of Neurological Disorders and Stroke (S.W.), Bethesda, Md.
Correspondence to Dr Werner Hacke, Department of Neurology, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany. E-mail werner_hacke{at}med.uni-heidelberg.de
Background and Purpose— Most acute ischemic stroke patients arrive after the 3-hour time window for recombinant tissue plasminogen activator (rtPA) administration. The Desmoteplase In Acute Ischemic Stroke trial (DIAS) was a dose-finding randomized trial designed to evaluate the safety and efficacy of intravenous desmoteplase, a highly fibrin-specific and nonneurotoxic thrombolytic agent, administered within 3 to 9 hours of ischemic stroke onset in patients with perfusion/diffusion mismatch on MRI.
Methods— DIAS was a placebo-controlled, double-blind, randomized, dose-finding phase II trial. Patients with National Institute of Health Stroke Scale (NIHSS) scores of 4 to 20 and MRI evidence of perfusion/diffusion mismatch were eligible. Of 104 patients, the first 47 (referred to as Part 1) were randomized to fixed doses of desmoteplase (25 mg, 37.5 mg, or 50 mg) or placebo. Because of an excessive rate of symptomatic intracranial hemorrhage (sICH), lower weight-adjusted doses escalating through 62.5 µg/kg, 90 µg/kg, and 125 µg/kg were subsequently investigated in 57 patients (referred to as Part 2). The safety endpoint was the rate of sICH. Efficacy endpoints were the rate of reperfusion on MRI after 4 to 8 hours and clinical outcome as assessed by NIHSS, modified Rankin scale, and Barthel Index at 90 days.
Results— Part 1 was terminated prematurely because of high rates of sICH with desmoteplase (26.7%). In Part 2, the sICH rate was 2.2%. No sICH occurred with placebo in either part. Reperfusion rates up to 71.4% (P=0.0012) were observed with desmoteplase (125 µg/kg) compared with 19.2% with placebo. Favorable 90-day clinical outcome was found in 22.2% of placebo-treated patients and between 13.3% (62.5 µg/kg; P=0.757) and 60.0% (125 µg/kg; P=0.0090) of desmoteplase-treated patients. Early reperfusion correlated favorably with clinical outcome (P=0.0028). Favorable outcome occurred in 52.5% of patients experiencing reperfusion versus 24.6% of patients without reperfusion.
Conclusions— Intravenous desmoteplase administered 3 to 9 hours after acute ischemic stroke in patients selected with perfusion/diffusion mismatch is associated with a higher rate of reperfusion and better clinical outcome compared with placebo. The sICH rate with desmoteplase was low, using doses up to 125 µg/kg.
Key Words: desmoteplase • magnetic resonance imaging • stroke • thrombolytic therapy
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