on March 30, 2006
Stroke. 2006
Published online before print March 30, 2006, doi: 10.1161/01.STR.0000217403.66996.6d
Published online before print March 30, 2006, doi: 10.1161/01.STR.0000217403.66996.6d
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Submitted on January 4, 2006
From The Cleveland Clinic (A.F.), Department of Neurology, Cleveland, Ohio; PAION Deutschland GmbH (D.E., Y.A.-R., M.S.), Aachen, Germany; the Stanford Stroke Center (G.A.), Palo Alto, Calif; the Western Infirmery (K.R.L.), University Department of Medicine & Therapeutics, Glasgow, United Kingdom; the University of Wisconsin (H.A.R.), Department of Radiology, Madison, Wis; the ClinResearch GmbH (C.S.), Köln, Germany; the NINDS (S.W.), Bethesda, Md; and the Department of Neurology (W.H.), University of Heidelberg, Heidelberg, Germany. * To whom correspondence should be addressed. E-mail: furlana{at}ccf.org.
Background and Purpose--Desmoteplase is a novel plasminogen activator with favorable features in vitro compared with available agents. This study evaluated safety and efficacy of intravenous (IV) desmoteplase in patients with perfusion/diffusion mismatch on MRI 3 to 9 hours after onset of acute ischemic stroke. Methods--DEDAS was a placebo-controlled, double-blind, randomized, dose-escalation study investigating doses of 90 µg/kg and 125 µg/kg desmoteplase. Eligibility criteria included baseline National Institute of Health Stroke Scale (NIHSS) scores of 4 to 20 and MRI evidence of perfusion/diffusion mismatch. The safety end point was the rate of symptomatic intracranial hemorrhage. Primary efficacy co-end points were MRI reperfusion 4 to 8 hours after treatment and good clinical outcome at 90 days. The primary analyses were intent-to-treat. Before unblinding, a target population, excluding patients violating specific MRI criteria, was defined. Results--Thirty-seven patients were randomized and received treatment (intent-to-treat; placebo: n=8; 90 µg/kg: n=14; 125 µg/kg: n=15). No symptomatic intracranial hemorrhage occurred. Reperfusion was achieved in 37.5% (95% CI [8.5; 75.5]) of placebo patients, 18.2% (2.3; 51.8) of patients treated with 90 µg/kg desmoteplase, and 53.3% (26.6; 78.7) of patients treated with 125 µg/kg desmoteplase. Good clinical outcome at 90 days occurred in 25.0% (3.2; 65.1) treated with placebo, 28.6% (8.4; 58.1) treated with 90 µg/kg desmoteplase and 60.0% (32.3; 83.7) treated with 125 µg/kg desmoteplase. In the target population (n=25), the difference compared with placebo increased and was statistically significant for good clinical outcome with 125 µg/kg desmoteplase (P=0.022). Conclusions--Treatment with IV desmoteplase 3 to 9 hours after ischemic stroke onset appears safe. At a dose of 125 µg/kg desmoteplase appeared to improve clinical outcome, especially in patients fulfilling all MRI criteria. The results of DEDAS generally support the results of its predecessor study, Desmoteplase in Acute Ischemic Stroke (DIAS).
Accepted on January 24, 2006
Dose Escalation of Desmoteplase for Acute Ischemic Stroke (DEDAS). Evidence of Safety and Efficacy 3 to 9 Hours After Stroke Onset
Anthony J. Furlan MD*;
Key words: desmoteplase • stroke • thrombolytic therapy
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