Recombinant tissue-type plasminogen activator (alteplase) for ischemic stroke 3 to 5 hours after symptom onset - The ATLANTIS study: A randomized controlled trial
Recombinant tissue-type plasminogen activator (alteplase) for ischemic stroke 3 to 5 hours after symptom onset - The ATLANTIS study: A randomized controlled trial
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DOI：
10.1001/jama.282.21.2019
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发表时间：
1999-12-01
影响因子：
120.7
通讯作者：
Hamilton, S
中科院分区：
文献类型：
--
作者：
Clark, WM;Wissman, S;Hamilton, S
重组组织型纤溶酶原激活剂（rt-PA）可改善急性缺血性卒中患者的预后，但目前批准的使用仅限于症状发作后3小时内。目的探讨急性缺血性脑卒中患者在发病后3 ~ 5 h内给予rt-PA的有效性和安全性。设计阿替普酶溶栓治疗急性缺血性脑卒中（ATLANTIS）研究是一项在1993年12月至1998年7月期间进行的III期、安慰剂对照、双盲随机化研究，在北美的140所大学和社区医院中，纳入了613例急性缺血性卒中患者的治疗人群，其中547例在症状发作后3 - 5小时内接受了治疗。另外39人在症状发作3小时内接受治疗，24人在症状发作5小时后接受治疗，干预组272例静脉注射rt-PA 0.9mg/kg，安慰剂275例静脉注射rt-PA 0.9mg/kg（美国国立卫生研究院卒中量表[NIHSS]评分小于或等于1）;次要终点包括第30天和第90天功能结局指标（Barthel指数、改良兰金量表和格拉斯哥结局量表）的良好恢复。结果在目标人群中，32%的安慰剂组和34%的rt-PA组患者在90天时恢复良好（P = 0.65）。任何次要功能结局指标均无差异。在前10天，rt-PA治疗显著增加了症状性脑出血（ICH）的发生率（1.1% vs 7.0% [P
Context Recombinant tissue-type plasminogen activator (rt-PA) improves outcomes for patients with acute ischemic stroke, but current approved use is limited to within 3 hours of symptom onset. This restricts the number of patients who can be treated, since most stroke patients present more than 3 hours after symptom onset.Objective To test the efficacy and safety of rt-PA in patients with acute ischemic stroke when administered between 3 and 5 hours after symptom onset.Design The Alteplase ThromboLysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) study is a phase 3, placebo-controlled, double-blind randomized study conducted between December 1993 and July 1998, with up to 90 days of follow-up.Setting One hundred forty university and community hospitals in North America.Patients An intent-to-treat population of 613 acute ischemic stroke patients was enrolled, with 547 of these treated as assigned within 3 to 5 hours of symptom onset. A total of 39 others were treated within 3 hours of symptom onset, 24 were treated more than 5 hours after symptom onset, and 3 never received any study drug.Intervention Administration of 0.9 mg/kg of rt-PA (n = 272) or placebo (n = 275) intravenously over 1 hour.Main Outcome Measures Primary efficacy was an excellent neurologic recovery at day 90 (National Institutes of Health Stroke Scale [NIHSS] score of less than or equal to 1); secondary end points included excellent recovery on functional outcome measures (Barthel index, modified Rankin scale, and Glasgow Outcome Scale) at days 30 and 90. Serious adverse events were also assessed.Results In the target population, 32% of the placebo and 34% of rt-PA patients had an excellent recovery at 90 days (P = .65). There were no differences on any of the secondary functional outcome measures. In the first 10 days treatment with rt-PA significantly increased the rate of symptomatic intracerebral hemorrhage (ICH) (1.1% vs 7.0% [P