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日进一卒，功不唐捐。 今天是咱们一起学习的第 909 天
静脉注射替萘普酶与阿替普酶治疗加拿大急性缺血性卒中的比较：一项实用、多中心、开放标签、注册链接、随机、对照、非劣效性试验 背景 阿替普酶静脉溶栓是标准。我们的目的是确定与此标准护理相比，单次给药的替萘普酶是否可能增加再灌注。 方法 在这项多中心、开放标签、平行组、注册表链接、随机对照试验（AcT）中，患者来自加拿大22个主要和综合卒中中心。如果患者年龄在18岁或以上，诊断为缺血性中风导致致残性神经功能缺损，在症状出现后4.5小时内出现，并且符合加拿大指南规定的溶栓治疗条件，则符合入选条件。符合条件的患者被随机分配（1:1），两组分别为静脉注射替萘普酶（0.25 mg/kg，最大25 mg）或静脉滴注阿替普酶（0.9 mg/kg，最大90 mg；0.09 mg/kg，然后60分钟输注剩余的0.81 mg/kg）。主要结果是在意向治疗（ITT）人群中通过盲法评估的治疗后90-120天改良Rankin量表（mRS）评分为0-1的患者比例。如果替萘普酶组和阿替普酶组之间达到主要结果的患者比例差异的95%置信区间低于-5%，则符合非劣效性。 结果 2019年12月10日至2022年1月25日期间，招募了1600名患者，并随机分配给替萘普酶（n=816）或阿替普酶（n=784），其中1577名患者被纳入ITT人群（n=806替萘普酶；n=771阿替普酶）。中位年龄为74岁（IQR 63-83），1577例患者中755例（47.9%）为女性，822例（52.1%）为男性。截至数据截止日期（2022年1月21日），替萘普酶组802名患者中的296名（36.9%）和阿替普酶组765名患者中的266名（34.8%）在90-120天的mRS评分为0-1（未经调整的风险差2.1%[95%CI-2.6至6.9]，符合预先指定的非劣性阈值）。在安全性分析中，替萘普酶组800例患者中有27例（3.4%）和阿替普酶组763例患者中有24例（3.2%）出现24小时症状性脑出血，796例患者中有122例（15.3%）和763例患者中有117例（15.4%）在开始治疗后90天内死亡 结论： 静脉注射替萘普酶（0.25 mg/kg）是所有符合溶栓标准的急性缺血性卒中患者替代阿替普酶的合理选择。 Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trialSummaryBackgroundIntravenous thrombolysis with alteplase bolus followed by infusion is a global standard of care for patients with acute ischaemic stroke. We aimed to determine whether tenecteplase given as a single bolus might increase reperfusion compared with this standard of care. MethodsIn this multicentre, open-label, parallel-group, registry-linked, randomised, controlled trial (AcT), patients were enrolled from 22 primary and comprehensive stroke centres across Canada. Patients were eligible for inclusion if they were aged 18 years or older, with a diagnosis of ischaemic stroke causing disabling neurological deficit, presenting within 4·5 h of symptom onset, and eligible for thrombolysis per Canadian guidelines. Eligible patients were randomly assigned (1:1), using a previously validated minimal sufficient balance algorithm to balance allocation by site and a secure real-time web-based server, to either intravenous tenecteplase (0·25 mg/kg to a maximum of 25 mg) or alteplase (0·9 mg/kg to a maximum of 90mg; 0·09 mg/kg as a bolus and then a 60 min infusion of the remaining 0·81 mg/kg). The primary outcome was the proportion of patients who had a modified Rankin Scale (mRS) score of 0–1 at 90–120 days after treatment, assessed via blinded review in the intention-to-treat (ITT) population (ie, all patients randomly assigned to treatment who did not withdraw consent). Non-inferiority was met if the lower 95% CI of the difference in the proportion of patients who met the primary outcome between the tenecteplase and alteplase groups was more than –5%. Safety was assessed in all patients who received any of either thrombolytic agent and who were reported as treated. The trial is registered with ClinicalTrials.gov, NCT03889249, and is closed to accrual. FindingsBetween Dec 10, 2019, and Jan 25, 2022, 1600 patients were enrolled and randomly assigned to tenecteplase (n=816) or alteplase (n=784), of whom 1577 were included in the ITT population (n=806 tenecteplase; n=771 alteplase). The median age was 74 years (IQR 63–83), 755 (47·9%) of 1577 patients were female and 822 (52·1%) were male. As of data cutoff (Jan 21, 2022), 296 (36·9%) of 802 patients in the tenecteplase group and 266 (34·8%) of 765 in the alteplase group had an mRS score of 0–1 at 90–120 days (unadjusted risk difference 2·1% [95% CI – 2·6 to 6·9], meeting the prespecified non-inferiority threshold). In safety analyses, 27 (3·4%) of 800 patients in the tenecteplase group and 24 (3·2%) of 763 in the alteplase group had 24 h symptomatic intracerebral haemorrhage and 122 (15·3%) of 796 and 117 (15·4%) of 763 died within 90 days of starting treatment InterpretationIntravenous tenecteplase (0·25 mg/kg) is a reasonable alternative to alteplase for all patients presenting with acute ischaemic stroke who meet standard criteria for thrombolysis.
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