Emergency administration of abciximab for treatment of patients with acute ischemic stroke:: Results of an international phase III trial -: Abciximab in emergency treatment of stroke trial (AbESTT-II)
Emergency administration of abciximab for treatment of patients with acute ischemic stroke:: Results of an international phase III trial -: Abciximab in emergency treatment of stroke trial (AbESTT-II)
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DOI：
10.1161/strokeaha.106.476648
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发表时间：
2008-01-01
期刊：
影响因子：
8.3
通讯作者：
Hacke, Werner
中科院分区：
文献类型：
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作者：
Adams, Harold P., Jr.;Effron, Mark B.;Hacke, Werner
背景与目的 - 先前一项随机、安慰剂对照、双盲研究表明，阿昔单抗在治疗急性缺血性脑卒中可能是安全有效的。当前的3期研究旨在测试阿昔单抗在急性缺血性脑卒中患者中症状发作后5小时内按计划治疗的相对有效性和安全性。
方法 - 一项国际性、随机、安慰剂对照、双盲3期试验，使用发病时间和卒中严重程度作为分层变量，在2个研究队列中测试阿昔单抗的静脉给药。计划招募1800名患者。主要队列招募那些在卒中发作5小时内可接受治疗的患者。一个伴随队列招募在卒中后5 - 6小时接受治疗的患者以及一个较小的在觉醒时发现卒中且能在3小时内接受治疗的患者队列。主要疗效指标是主要队列受试者中在3个月时根据卒中基线严重程度调整后的改良Rankin量表二分法评分。主要安全结局是卒中后5天内发生的有症状或致命性颅内出血的发生率。
结果 - 由于获益 - 风险状况不佳，在独立的安全性和有效性监测委员会的建议下，所有队列共招募808名患者后该试验提前终止。在3个月时，主要队列中约33%接受安慰剂治疗的患者（72/218）和32%接受阿昔单抗治疗的患者（71/221；P = 0.944）被判定对治疗有良好反应。改良Rankin量表的结果分布在治疗组和对照组之间相似。在入组后5天内，主要队列中约5.5%接受阿昔单抗治疗的患者和0.5%接受安慰剂治疗的患者发生有症状或致命性颅内出血（P = 0.002）。该试验也未表明在伴随队列和觉醒队列患者中使用阿昔单抗的结果有改善。尽管患者数量较少，但在接受阿昔单抗治疗的觉醒人群患者中，5天内出血率增加（13.6%对比安慰剂组的5%）。
结论 - 无论研究的终点或人群如何，本试验均未证明静脉注射阿昔单抗治疗急性缺血性脑卒中患者的安全性或有效性。在主要队列和觉醒队列中，有症状或致命性颅内出血的发生率增加。
Background and Purpose-A previous randomized, placebo-controlled, double-blind study suggested that abciximab may be safe and effective in treatment of acute ischemic stroke. The current phase 3 study was planned to test the relative efficacy and safety of abciximab in patients with acute ischemic stroke with planned treatment within 5 hours since symptoms onset.Methods-An international, randomized, placebo-controlled, double-blind phase 3 trial tested intravenous administration of abciximab in 2 study cohorts using stratification variables of time since onset and stroke severity. The planned enrollment was 1800 patients. The primary cohort enrolled those patients who could be treated within 5 hours of onset of stroke. A companion cohort enrolled patients that were treated 5 to 6 hours after stroke as well as a smaller cohort of patients who could be treated within 3 hours of stroke present on awakening. The primary efficacy measure was the dichotomous modified Rankin Scale score at 3 months as adjusted to the baseline severity of stroke among subjects in the primary cohort. The primary safety outcome was the rate of symptomatic or fatal intracranial hemorrhage that occurred within 5 days of stroke.Results-The trial was terminated prematurely after 808 patients in all cohorts were enrolled by recommendation of an independent safety and efficacy monitoring board due to an unfavorable benefit-risk profile. At 3 months, approximately 33% of patients assigned placebo (72/218) and 32% of patients assigned abciximab (71/221; P = 0.944) in the primary cohort were judged to have a favorable response to treatment. The distributions of outcomes on the modified Rankin Scale were similar between the treated and control groups. Within 5 days of enrollment, approximate to 5.5% of abciximab-treated and 0.5% of placebo-treated patients in the primary cohort had symptomatic or fatal intracranial hemorrhage (P = 0.002). The trial also did not demonstrate an improvement in outcomes with abciximab among patients in the companion and wake-up cohorts. Although the number of patients was small, an increased rate of hemorrhage was noted within 5 days among patients in the wake-up population who received abciximab (13.6% versus 5% for placebo).Conclusions-This trial did not demonstrate either safety or efficacy of intravenous administration of abciximab for the treatment of patients with acute ischemic stroke regardless of end point or population studied. There was an increased rate of symptomatic or fatal intracranial hemorrhage in the primary and wake-up cohorts.