Intravenous desmoteplase in patients with acute ischaemic stroke selected by MRI perfusion-diffusion weighted imaging or perfusion CT (DIAS-2): a prospective, randomised, double-blind, placebo-controlled study.
Intravenous desmoteplase in patients with acute ischaemic stroke selected by MRI perfusion-diffusion weighted imaging or perfusion CT (DIAS-2): a prospective, randomised, double-blind, placebo-controlled study.
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DOI：
10.1016/s1474-4422(08)70267-9
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发表时间：
2009-02
期刊：
影响因子：
48
通讯作者：
Warach, Steven
中科院分区：
文献类型：
--
作者：
Hacke, Werner;Furlan, Anthony J.;Al-Rawi, Yasir;Davalos, Antoni;Fiebach, Jochen B.;Gruber, Franz;Kaste, Markku;Lipka, Leslie J.;Pedraza, Salvador;Ringleb, Peter A.;Rowley, Howard A.;Schneider, Dietmar;Schwamm, Lee H.;Leal, Joaquin Serena;Soehngen, Mariola;Teal, Phil A.;Wilhelm-Ogunbiyi, Karin;Wintermark, Max;Warach, Steven
先前的研究表明，去氨普酶（一种新型纤溶酶原激活剂）对于通过磁共振灌注成像 (PI) 和弥散加权成像 (DWI) 识别的推定组织处于危险中的患者，在中风症状出现 3-9 小时后给予，具有临床益处。在这项随机、安慰剂对照、双盲、剂量范围的研究中，患有急性缺血性中风且在 MRI 或 CT 成像中发现有风险组织的患者在中风症状出现后 3-9 小时内被随机分配 (1:1:1) 至 90 µg/kg 去氨普酶、125 µg/kg 去氨普酶或安慰剂。主要终点是第 90 天的临床缓解率，定义为美国国立卫生研究院卒中量表 (NIHSS) 评分改善为 8 分或以上或 NIHSS 评分为 1 分或以下、改良 Rankin 量表评分为 0-2 分以及 Barthel 指数为 75-100 的综合结果。次要终点包括基线和第 30 天之间病变体积的变化、症状性颅内出血率和死亡率。分析是按意向治疗进行的。本研究已在 ClinicalTrials.gov 注册，NCT00111852。 2005年6月至2007年3月期间，193名患者被随机分组，186名患者接受治疗：57名接受90 µg/kg去氨普酶； 66 人接受了 125 µg/kg 去氨普酶； 63 人接受安慰剂。 158 名患者完成了这项研究。 NIHSS 基线评分中位数为 9 分（IQR 6-14）分，30%（179 名患者中的 53 名）就诊时有明显的血管闭塞。核心病变和错配体积较小（中位体积分别为10·6 cm3 和52·5 cm3）。第 90 天时，90 µg/kg 去氨普酶的临床反应率为 47%（57 人中的 27 人），125 µg/kg 去氨普酶为 36%（66 人中的 24 人），安慰剂为 46%（63 人中的 29 人）。病变体积的中位变化为： 90 µg/kg 去氨普酶 14·0% (0·5 cm3)； 125 µg/kg 去氨普酶 10·8%（0·3 cm3 安慰剂 −10·0%（−0·9 cm3）。90 µg/kg 去氨普酶的症状性颅内出血率为 3·5%（57 人中的 2 人），125 µg/kg 去氨普酶为 4·5%（66 人中的 3 人），安慰剂为 0%。死亡率为 11%（90 µg/kg 去氨普酶组为 5%（57 人中的 3 人）；125 µg/kg 去氨普酶组为 21%（66 人中的 14 人）；安慰剂组为 6%（63 人中的 4 人）。DIAS-2 研究并未显示中风发作后 3-9 小时给予去氨普酶的益处。安慰剂组的高反应率可以用轻度来解释。记录的中风（低基线 NIHSS 评分、小核心病变以及与无血管闭塞相关的小错配体积），这可能降低检测去氨普酶任何作用的可能性。
Previous studies have suggested that desmoteplase, a novel plasminogen activator, has clinical benefit when given 3–9 h after the onset of the symptoms of stroke in patients with presumptive tissue at risk that is identified by magnetic resonance perfusion imaging (PI) and diffusion-weighted imaging (DWI). In this randomised, placebo-controlled, double-blind, dose-ranging study, patients with acute ischaemic stroke and tissue at risk seen on either MRI or CT imaging were randomly assigned (1:1:1) to 90 µg/kg desmoteplase, 125 µg/kg desmoteplase, or placebo within 3–9 h after the onset of symptoms of stroke. The primary endpoint was clinical response rates at day 90, defined as a composite of improvement in National Institutes of Health stroke scale (NIHSS) score of 8 points or more or an NIHSS score of 1 point or less, a modified Rankin scale score of 0–2 points, and a Barthel index of 75–100. Secondary endpoints included change in lesion volume between baseline and day 30, rates of symptomatic intracranial haemorrhage, and mortality rates. Analysis was by intention to treat. This study registered with ClinicalTrials.gov, NCT00111852. Between June, 2005, and March, 2007, 193 patients were randomised, and 186 patients received treatment: 57 received 90 µg/kg desmoteplase; 66 received 125 µg/kg desmoteplase; and 63 received placebo. 158 patients completed the study. The median baseline NIHSS score was 9 (IQR 6–14) points, and 30% (53 of 179) of the patients had a visible occlusion of a vessel at presentation. The core lesion and the mismatch volumes were small (median volumes were 10·6 cm3 and 52·5 cm3, respectively). The clinical response rates at day 90 were 47% (27 of 57) for 90 µg/kg desmoteplase, 36% (24 of 66) for 125 µg/kg desmoteplase, and 46% (29 of 63) for placebo. The median changes in lesion volume were: 90 µg/kg desmoteplase 14·0% (0·5 cm3); 125 µg/kg desmoteplase 10·8% (0·3 cm3 placebo −10·0% (−0·9 cm3). The rates of symptomatic intracranial haemorrhage were 3·5% (2 of 57) for 90 µg/kg desmoteplase, 4·5% (3 of 66) for 125 µg/kg desmoteplase, and 0% for placebo. The overall mortality rate was 11% (5% [3 of 57] for 90 µg/kg desmoteplase; 21% [14 of 66] for 125 µg/kg desmoteplase; and 6% [4 of 63] for placebo). The DIAS-2 study did not show a benefit of desmoteplase given 3–9 h after the onset of stroke. The high response rate in the placebo group could be explained by the mild strokes recorded (low baseline NIHSS scores, small core lesions, and small mismatch volumes that were associated with no vessel occlusions), which possibly reduced the potential to detect any effect of desmoteplase.