Furlan Anthony J, Eyding Dirk, Albers Gregory W, Al-Rawi Yasir, Lees Kennedy R, Rowley Howard A, Sachara Christian, Soehngen Mariola, Warach Steven, Hacke Werner
Department of Neurology, The Cleveland Clinic, Cleveland, OH 44195, USA.
Stroke. 2006 May;37(5):1227-31. doi: 10.1161/01.STR.0000217403.66996.6d. Epub 2006 Mar 30.
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.
DEDAS was a placebo-controlled, double-blind, randomized, dose-escalation study investigating doses of 90 microg/kg and 125 microg/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.
Thirty-seven patients were randomized and received treatment (intent-to-treat; placebo: n=8; 90 microg/kg: n=14; 125 microg/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 microg/kg desmoteplase, and 53.3% (26.6; 78.7) of patients treated with 125 microg/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 microg/kg desmoteplase and 60.0% (32.3; 83.7) treated with 125 microg/kg desmoteplase. In the target population (n=25), the difference compared with placebo increased and was statistically significant for good clinical outcome with 125 microg/kg desmoteplase (P=0.022).
Treatment with IV desmoteplase 3 to 9 hours after ischemic stroke onset appears safe. At a dose of 125 microg/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).
去氨普酶是一种新型纤溶酶原激活剂，与现有药物相比，在体外具有良好特性。本研究评估了急性缺血性卒中发病3至9小时后，静脉注射去氨普酶对MRI显示灌注/弥散不匹配患者的安全性和有效性。
DEDAS是一项安慰剂对照、双盲、随机、剂量递增研究，研究了90μg/kg和125μg/kg去氨普酶剂量。入选标准包括基线美国国立卫生研究院卒中量表（NIHSS）评分为4至20分以及MRI显示灌注/弥散不匹配。安全终点是症状性颅内出血发生率。主要疗效共同终点是治疗后4至8小时的MRI再灌注以及90天时良好的临床结局。主要分析采用意向性治疗。在揭盲前，定义了一个排除违反特定MRI标准患者的目标人群。
37例患者被随机分组并接受治疗（意向性治疗；安慰剂：n = 8；90μg/kg：n = 14；125μg/kg：n = 15）。未发生症状性颅内出血。安慰剂组37.5%（95%CI[8.5；75.5]）的患者实现再灌注，90μg/kg去氨普酶治疗组为18.2%（2.3；51.8），125μg/kg去氨普酶治疗组为53.3%（26.6；78.7）。安慰剂治疗组90天时良好临床结局发生率为25.0%（3.2；65.1），90μg/kg去氨普酶治疗组为28.6%（8.4；58.1），125μg/kg去氨普酶治疗组为60.0%（32.3；83.7）。在目标人群（n = 25）中，与安慰剂相比，125μg/kg去氨普酶治疗组良好临床结局的差异增大且具有统计学意义（P = 0.022）。
缺血性卒中发病3至9小时后静脉注射去氨普酶治疗似乎安全。125μg/kg剂量的去氨普酶似乎可改善临床结局，尤其是在符合所有MRI标准的患者中。DEDAS的结果总体上支持其前期研究“急性缺血性卒中中的去氨普酶（DIAS）”的结果。
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