Department of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.
The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia.
JAMA. 2020 Apr 7;323(13):1257-1265. doi: 10.1001/jama.2020.1511.
Intravenous thrombolysis with tenecteplase improves reperfusion prior to endovascular thrombectomy for ischemic stroke compared with alteplase.
To determine whether 0.40 mg/kg of tenecteplase safely improves reperfusion before endovascular thrombectomy vs 0.25 mg/kg of tenecteplase in patients with large vessel occlusion ischemic stroke.
DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial at 27 hospitals in Australia and 1 in New Zealand using open-label treatment and blinded assessment of radiological and clinical outcomes. Patients were enrolled from December 2017 to July 2019 with follow-up until October 2019. Adult patients (N = 300) with ischemic stroke due to occlusion of the intracranial internal carotid, \basilar, or middle cerebral artery were included less than 4.5 hours after symptom onset using standard intravenous thrombolysis eligibility criteria.
Open-label tenecteplase at 0.40 mg/kg (maximum, 40 mg; n = 150) or 0.25 mg/kg (maximum, 25 mg; n = 150) given as a bolus before endovascular thrombectomy.
The primary outcome was reperfusion of greater than 50% of the involved ischemic territory prior to thrombectomy, assessed by consensus of 2 blinded neuroradiologists. Prespecified secondary outcomes were level of disability at day 90 (modified Rankin Scale [mRS] score; range, 0-6); mRS score of 0 to 1 (freedom from disability) or no change from baseline at 90 days; mRS score of 0 to 2 (functional independence) or no change from baseline at 90 days; substantial neurological improvement at 3 days; symptomatic intracranial hemorrhage within 36 hours; and all-cause death.
All 300 patients who were randomized (mean age, 72.7 years; 141 [47%] women) completed the trial. The number of participants with greater than 50% reperfusion of the previously occluded vascular territory was 29 of 150 (19.3%) in the 0.40 mg/kg group vs 29 of 150 (19.3%) in the 0.25 mg/kg group (unadjusted risk difference, 0.0% [95% CI, -8.9% to -8.9%]; adjusted risk ratio, 1.03 [95% CI, 0.66-1.61]; P = .89). Among the 6 secondary outcomes, there were no significant differences in any of the 4 functional outcomes between the 0.40 mg/kg and 0.25 mg/kg groups nor in all-cause deaths (26 [17%] vs 22 [15%]; unadjusted risk difference, 2.7% [95% CI, -5.6% to 11.0%]) or symptomatic intracranial hemorrhage (7 [4.7%] vs 2 [1.3%]; unadjusted risk difference, 3.3% [95% CI, -0.5% to 7.2%]).
Among patients with large vessel occlusion ischemic stroke, a dose of 0.40 mg/kg, compared with 0.25 mg/kg, of tenecteplase did not significantly improve cerebral reperfusion prior to endovascular thrombectomy. The findings suggest that the 0.40-mg/kg dose of tenecteplase does not confer an advantage over the 0.25-mg/kg dose in patients with large vessel occlusion ischemic stroke in whom endovascular thrombectomy is planned.
ClinicalTrials.gov Identifier: NCT03340493.
重要性：与阿替普酶相比，替奈普酶静脉溶栓可改善血管内血栓切除术治疗缺血性脑卒中前的再灌注。
目的：确定在计划进行血管内血栓切除术的大血管闭塞性缺血性脑卒中患者中，与 0.25mg/kg 替奈普酶相比，0.40mg/kg 替奈普酶是否能更安全地改善血管内血栓切除术前的再灌注。
设计、地点和参与者：在澳大利亚 27 家医院和新西兰 1 家医院进行的随机临床试验，使用开放标签治疗和盲法评估影像学和临床结局。2017 年 12 月至 2019 年 7 月期间招募患者，随访至 2019 年 10 月。使用标准静脉溶栓入选标准，将小于 4.5 小时起病的颅内颈内动脉、基底动脉或大脑中动脉闭塞的成人（N=300）患者纳入研究。
干预措施：血管内血栓切除术前给予开放标签替奈普酶 0.40mg/kg（最大剂量 40mg；n=150）或 0.25mg/kg（最大剂量 25mg；n=150），作为推注给药。
主要结局和测量指标：主要结局是由 2 位盲法神经放射学家一致评估的血管内血栓切除术前大于受累缺血区域 50%的再灌注程度。预先设定的次要结局是 90 天的残疾程度（改良 Rankin 量表[mRS]评分；范围 0-6）；90 天时 mRS 评分为 0 至 1（无残疾）或与基线相比无变化；90 天时 mRS 评分为 0 至 2（功能独立）或与基线相比无变化；3 天内有明显的神经改善；36 小时内症状性颅内出血；以及全因死亡。
结果：所有 300 名随机分组的患者（平均年龄 72.7 岁；141[47%]名女性）均完成了试验。0.40mg/kg 组和 0.25mg/kg 组中，闭塞血管前大于 50%再灌注的患者人数分别为 150 例中的 29 例（19.3%）和 150 例中的 29 例（19.3%）（未调整的风险差异，0.0%[95%CI，-8.9%至-8.9%]；调整后的风险比，1.03[95%CI，0.66-1.61]；P=0.89）。在 6 项次要结局中，0.40mg/kg 组和 0.25mg/kg 组之间，4 项功能结局均无显著差异，全因死亡率也无显著差异（26[17%]vs 22[15%]；未调整的风险差异，2.7%[95%CI，-5.6%至 11.0%]）或症状性颅内出血（7[4.7%]vs 2[1.3%]；未调整的风险差异，3.3%[95%CI，-0.5%至 7.2%]）。
结论和相关性：在大血管闭塞性缺血性脑卒中患者中，与 0.25mg/kg 相比，0.40mg/kg 剂量的替奈普酶并未显著改善血管内血栓切除术前的脑再灌注。这些发现表明，在计划进行血管内血栓切除术的大血管闭塞性缺血性脑卒中患者中，与 0.25mg/kg 相比，0.40mg/kg 剂量的替奈普酶并没有优势。
试验注册：ClinicalTrials.gov 标识符：NCT03340493。
