Department of Neurology, Nippon Medical School, Tokyo, Japan.
Division of Stroke Prevention and Treatment, Department of Neurosurgery, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
JAMA. 2021 Jan 19;325(3):244-253. doi: 10.1001/jama.2020.23522.
Whether intravenous thrombolysis is needed in combination with mechanical thrombectomy in patients with acute large vessel occlusion stroke is unclear.
To examine whether mechanical thrombectomy alone is noninferior to combined intravenous thrombolysis plus mechanical thrombectomy for favorable poststroke outcome.
DESIGN, SETTING, AND PARTICIPANTS: Investigator-initiated, multicenter, randomized, open-label, noninferiority clinical trial in 204 patients with acute ischemic stroke due to large vessel occlusion enrolled at 23 hospital networks in Japan from January 1, 2017, to July 31, 2019, with final follow-up on October 31, 2019.
Patients were randomly assigned to mechanical thrombectomy alone (n = 101) or combined intravenous thrombolysis (alteplase at a 0.6-mg/kg dose) plus mechanical thrombectomy (n = 103).
The primary efficacy end point was a favorable outcome defined as a modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]) of 0 to 2 at 90 days, with a noninferiority margin odds ratio of 0.74, assessed using a 1-sided significance threshold of .025 (97.5% CI). There were 7 prespecified secondary efficacy end points, including mortality by day 90. There were 4 prespecified safety end points, including any intracerebral hemorrhage and symptomatic intracerebral hemorrhage within 36 hours.
Among 204 patients (median age, 74 years; 62.7% men; median National Institutes of Health Stroke Scale score, 18), all patients completed the trial. Favorable outcome occurred in 60 patients (59.4%) in the mechanical thrombectomy alone group and 59 patients (57.3%) in the combined intravenous thrombolysis plus mechanical thrombectomy group, with no significant between-group difference (difference, 2.1% [1-sided 97.5% CI, -11.4% to ∞]; odds ratio, 1.09 [1-sided 97.5% CI, 0.63 to ∞]; P = .18 for noninferiority). Among the 7 secondary efficacy end points and 4 safety end points, 10 were not significantly different, including mortality at 90 days (8 [7.9%] vs 9 [8.7%]; difference, -0.8% [95% CI, -9.5% to 7.8%]; odds ratio, 0.90 [95% CI, 0.33 to 2.43]; P > .99). Any intracerebral hemorrhage was observed less frequently in the mechanical thrombectomy alone group than in the combined group (34 [33.7%] vs 52 [50.5%]; difference, -16.8% [95% CI, -32.1% to -1.6%]; odds ratio, 0.50 [95% CI, 0.28 to 0.88]; P = .02). Symptomatic intracerebral hemorrhage was not significantly different between groups (6 [5.9%] vs 8 [7.7%]; difference, -1.8% [95% CI, -9.7% to 6.1%]; odds ratio, 0.75 [95% CI, 0.25 to 2.24]; P = .78).
Among patients with acute large vessel occlusion stroke, mechanical thrombectomy alone, compared with combined intravenous thrombolysis plus mechanical thrombectomy, failed to demonstrate noninferiority regarding favorable functional outcome. However, the wide confidence intervals around the effect estimate also did not allow a conclusion of inferiority.
umin.ac.jp/ctr Identifier: UMIN000021488.
对于急性大血管闭塞性卒中患者，静脉溶栓是否联合机械取栓仍不明确。
检验机械取栓是否不劣于单纯静脉溶栓联合机械取栓对改善卒中后结局。
设计、地点和参与者：多中心、随机、开放标签、非劣效性临床试验，纳入了 2017 年 1 月 1 日至 2019 年 7 月 31 日期间，日本 23 家医院网络中 204 例因大血管闭塞导致的急性缺血性卒中患者，最终随访时间为 2019 年 10 月 31 日。
患者被随机分为机械取栓组（n=101）或单纯静脉溶栓（阿替普酶 0.6mg/kg 剂量）联合机械取栓组（n=103）。
主要疗效终点为 90 天改良 Rankin 量表评分（范围：0 分[无症状]至 6 分[死亡]）为 0 至 2 分，非劣效性边缘比值比为 0.74，使用单侧显著性阈值为 0.025（97.5%置信区间）评估。有 7 个预先指定的次要疗效终点，包括 90 天死亡率。有 4 个预先指定的安全性终点，包括 36 小时内任何颅内出血和症状性颅内出血。
在 204 例患者中（中位年龄 74 岁；62.7%为男性；中位国立卫生研究院卒中量表评分 18 分），所有患者均完成了试验。机械取栓组有 60 例（59.4%）和单纯静脉溶栓联合机械取栓组有 59 例（57.3%）患者预后良好，两组间无显著差异（差异，2.1%[单侧 97.5%置信区间，-11.4%至 ∞]；比值比，1.09[单侧 97.5%置信区间，0.63 至 ∞]；P=0.18 非劣效性）。在 7 个次要疗效终点和 4 个安全性终点中，有 10 个无显著差异，包括 90 天死亡率（8 [7.9%] vs 9 [8.7%]；差异，-0.8%[95%置信区间，-9.5%至 7.8%]；比值比，0.90[95%置信区间，0.33 至 2.43]；P＞0.99）。机械取栓组颅内出血发生率低于联合组（34 [33.7%] vs 52 [50.5%]；差异，-16.8%[95%置信区间，-32.1%至 -1.6%]；比值比，0.50[95%置信区间，0.28 至 0.88]；P=0.02）。两组症状性颅内出血无显著差异（6 [5.9%] vs 8 [7.7%]；差异，-1.8%[95%置信区间，-9.7%至 6.1%]；比值比，0.75[95%置信区间，0.25 至 2.24]；P=0.78）。
在急性大血管闭塞性卒中患者中，与单纯静脉溶栓联合机械取栓相比，机械取栓单独治疗未能显示在改善功能结局方面具有非劣效性。然而，效应估计的置信区间也不允许得出劣效性的结论。
umin.ac.jp/ctr 标识符：UMIN000021488。
