Safety and efficacy of desmoteplase given 3-9 h after ischaemic stroke in patients with occlusion or high-grade stenosis in major cerebral arteries (DIAS-3): a double-blind, randomised, placebo-controlled phase 3 trial
Safety and efficacy of desmoteplase given 3-9 h after ischaemic stroke in patients with occlusion or high-grade stenosis in major cerebral arteries (DIAS-3): a double-blind, randomised, placebo-controlled phase 3 trial
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DOI：
10.1016/s1474-4422(15)00047-2
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发表时间：
2015-06-01
期刊：
影响因子：
48
通讯作者：
Shuaib, Ashfaq
中科院分区：
文献类型：
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作者：
Albers, Gregory W.;von Kummer, Ruediger;Shuaib, Ashfaq
背景目前对缺血性卒中的溶栓治疗仅限于症状发作后3-4.5小时。我们的目的是评估去氨普酶，一种纤维蛋白依赖性纤溶酶原激活剂，在症状发作后3小时和9小时之间给予脑主要动脉闭塞或高度狭窄患者的安全性和有效性。我们从17个国家的77家医院招募了患有缺血性中风和主要脑动脉闭塞或高度狭窄的患者。我们使用计算机生成的随机化列表，根据基线国立卫生研究院卒中量表和年龄分层，以1：1的比例将患者随机分配至症状发作后3-9小时给予去氨普酶（90 μ g/kg）或安慰剂治疗组。患者、研究者、工作人员和资助者对治疗分配不知情。主要结局是所有接受治疗的患者在第90天的改良兰金量表评分（0-2）良好，这些患者至少有一次改良兰金量表的基线后测量结果。在所有随机分配的接受研究药物的患者中评估安全性。该试验注册于ClinicalTrials.gov，注册号为NCT 00790920。研究结果在2009年2月6日至2013年11月27日期间，我们招募了492名患者，随机分配247名接受去氨普酶治疗，245名接受安慰剂治疗（去氨普酶组236名，安慰剂组237名被纳入主要终点分析）。安慰剂组从卒中发作至治疗的中位时间为6.9 h（IQR 5.7-8.0），去氨普酶组为7-0 h（6.0-7.9）。121例（51%）接受去氨普酶治疗的患者和118例（50%）接受安慰剂治疗的患者在第90天的改良Ranldn量表评分（0-2分）（校正比值比1.20，95%CI 0-79-1-81，p=0.40）。240例接受去氨普酶治疗的患者中有24例（10%）死亡，而238例接受安慰剂治疗的患者中有23例（10%）死亡。240例接受去氨普酶治疗的患者中有64例（27%）发生严重不良事件，而238例接受安慰剂治疗的患者中有69例（29%）发生严重不良事件;症状性颅内出血的频率（去氨普酶组6例[3%]患者vs安慰剂组5例[2%]患者），症状性脑水肿（五[2%]对四[2%]），和大出血（10人[4%]对15人[6%]）解释当给予缺血性卒中和主要脑动脉闭塞超过3小时的患者时，去氨替普酶治疗不会引起安全性问题，也不会改善功能结局。症状发作。
Background Current treatment of ischaemic stroke with thrombolytic therapy is restricted to 3-4.5 h after symptom onset. We aimed to assess the safety and efficacy of desmoteplase, a fibrin-dependent plasminogen activator, given between 3 h and 9 h after symptom onset in patients with occlusion or high-grade stenosis in major cerebral arteries.Methods In a prospective, double-blind, multicentre, parallel-group, randomised trial, we enrolled patients from 77 hospitals in 17 countries who had ischaemic stroke and occlusion or high-grade stenosis in major cerebral arteries. We randomly assigned patients in a 1:1 ratio, using computer-generated randomisation lists with stratification for baseline National Institutes of Health Stroke Scale and age, to treatment with desmoteplase (90 mu g/kg) given 3-9 h after symptom onset or to placebo. Patients, investigators, staff, and the funder were masked to treatment assignment. The primary outcome was a favourable modified Rankin Scale score (0-2) at day 90 in all treated patients who had at least one postbaseline measurement of the modified Rankin Scale. Safety was assessed in all randomly assigned patients who received study drugs. This trial is registered with ClinicalTrials.gov, number NCT00790920.Findings Between Feb 6,2009, and Nov 27,2013, we enrolled 492 patients and randomly assigned 247 to desmoteplase and 245 to placebo (236 in the desmoteplase group and 237 in the placebo group were included in the analysis of the primary endpoint). Median time from stroke onset to treatment was 6.9 h (IQR 5.7-8.0) for placebo and 7-0 h (6.0-7.9) for desmoteplase. Modified Ranldn Scale score (0-2) at day 90 occurred in 121 (51%) patients given desmoteplase and 118 (50%) patients given placebo (adjusted odds ratio 1.20,95% CI 0-79-1-81, p=0.40). 24 (10%) of 240 patients given desmoteplase died compared with 23 (10%) of 238 patients given placebo. Serious adverse events occurred in 64 (27%) of 240 patients receiving desmoteplase compared with 69 (29%) of 238 patients receiving placebo; frequency of symptomatic intracranial haemorrhage (six [3%] patients in the desmoteplase group vs five [2%] in the placebo group), symptomatic cerebral oedema (five [2%] vs four [2%]), and major haemorrhage (ten [4%] vs 15 [6%]) was much the same between treatment groups.Interpretation Treatment with desmoteplase did not cause safety concerns and did not improve functional outcome when given to patients who had ischaemic stroke and major cerebral artery occlusion beyond 3 h of symptom onset.