The Desmoteplase in Acute Ischemic Stroke Trial (DIAS): A phase II MRI-based 9-hour window acute stroke thrombolysis trial with intravenous desmoteplase

Werner Hacke, Greg Albers, Yasir Al-Rawi, Julien Bogousslavsky, Antonio Davalos, Michael Eliasziw, Michael Fischer, Anthony Furlan, Markku Kaste, Kennedy R. Lees, Mariola Soehngen, Steven Warach

Research output: Contribution to journalArticle

855 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)66-73
Number of pages8
JournalStroke
Volume36
Issue number1
DOIs
StatePublished - Jan 2005

Fingerprint

Stroke
Intracranial Hemorrhages
Reperfusion
Placebos
Perfusion
National Institutes of Health (U.S.)
salivary plasminogen activator alpha 1, Desmodus rotundus
Safety
Fibrinolytic Agents
Tissue Plasminogen Activator
Fibrin
Weights and Measures

Keywords

  • Desmoteplase
  • Magnetic resonance imaging
  • Stroke
  • Thrombolytic therapy

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

Cite this

The Desmoteplase in Acute Ischemic Stroke Trial (DIAS) : A phase II MRI-based 9-hour window acute stroke thrombolysis trial with intravenous desmoteplase. / Hacke, Werner; Albers, Greg; Al-Rawi, Yasir; Bogousslavsky, Julien; Davalos, Antonio; Eliasziw, Michael; Fischer, Michael; Furlan, Anthony; Kaste, Markku; Lees, Kennedy R.; Soehngen, Mariola; Warach, Steven.

In: Stroke, Vol. 36, No. 1, 01.2005, p. 66-73.

Research output: Contribution to journalArticle

Hacke, W, Albers, G, Al-Rawi, Y, Bogousslavsky, J, Davalos, A, Eliasziw, M, Fischer, M, Furlan, A, Kaste, M, Lees, KR, Soehngen, M & Warach, S 2005, 'The Desmoteplase in Acute Ischemic Stroke Trial (DIAS): A phase II MRI-based 9-hour window acute stroke thrombolysis trial with intravenous desmoteplase', Stroke, vol. 36, no. 1, pp. 66-73. https://doi.org/10.1161/01.STR.0000149938.08731.2c
Hacke, Werner ; Albers, Greg ; Al-Rawi, Yasir ; Bogousslavsky, Julien ; Davalos, Antonio ; Eliasziw, Michael ; Fischer, Michael ; Furlan, Anthony ; Kaste, Markku ; Lees, Kennedy R. ; Soehngen, Mariola ; Warach, Steven. / The Desmoteplase in Acute Ischemic Stroke Trial (DIAS) : A phase II MRI-based 9-hour window acute stroke thrombolysis trial with intravenous desmoteplase. In: Stroke. 2005 ; Vol. 36, No. 1. pp. 66-73.
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abstract = "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.",
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T1 - The Desmoteplase in Acute Ischemic Stroke Trial (DIAS)

T2 - A phase II MRI-based 9-hour window acute stroke thrombolysis trial with intravenous desmoteplase

AU - Hacke, Werner

AU - Albers, Greg

AU - Al-Rawi, Yasir

AU - Bogousslavsky, Julien

AU - Davalos, Antonio

AU - Eliasziw, Michael

AU - Fischer, Michael

AU - Furlan, Anthony

AU - Kaste, Markku

AU - Lees, Kennedy R.

AU - Soehngen, Mariola

AU - Warach, Steven

PY - 2005/1

Y1 - 2005/1

N2 - 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.

AB - 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.

KW - Desmoteplase

KW - Magnetic resonance imaging

KW - Stroke

KW - Thrombolytic therapy

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