?
当前位置:澳门黄金赌城 > 小柯机器人 >详情
静脉注射替奈普酶治疗急性缺血性卒中不逊于阿替普酶标准治疗
作者:小柯机器人 发布时间:2022/6/30 20:06:14

加拿大卡尔加里大学Bijoy K Menon团队研究了静脉注射替奈普酶与阿替普酶治疗急性缺血性卒中的效果。2022年6月29日出版的《柳叶刀》发表了这项成果。

阿替普酶静脉溶栓后输注是急性缺血性脑卒中患者的全球护理标准。该研究旨在确定与此标准治疗相比,单次注射替奈普酶是否可能增加再灌注。

研究组在加拿大22个初级和综合中风中心进行了一项多中心、开放标签、平行组、注册表链接、随机、对照试验,若患者年龄在18岁及以上,被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,且符合加拿大指南规定的溶栓治疗条件,则可入组。将患者按1:1随机分配,使用之前验证过的最小充分平衡算法来平衡机构分配和安全的实时网络服务器,患者分别接受静脉注射替奈普酶或阿替普酶。

在意向治疗(ITT)人群中通过盲法评估主要结局,即在治疗后90-120天,改良Rankin量表(mRS)得分为0-1的患者比例(即,所有随机分配接受治疗但未撤回同意书的患者)。若替奈普酶组和阿替普酶组达到主要结局的患者比例的95%置信区间下限大于–5%,则符合非劣效性。对所有接受任何一种溶栓剂治疗并报告接受治疗的患者进行安全性评估。

2019年12月10日至2022年1月25日,共有1600名患者被纳入研究,其中替奈普酶组816例,阿替普酶组784例;共1577名患者被纳入ITT人群(替奈普酶组806例,阿替普酶组771例)。患者的中位年龄为74岁,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(2022年1月21日),替奈普酶组802名患者中有296名(36.9%)在90-120天时的mRS评分为0-1,阿替普酶组765名患者中有266名(34.8%),未校正风险差为2.1%。在安全性分析中,替奈普酶组800名患者中有27名(3.4%)出现24小时症状性脑出血,阿替普酶组763名患者中有24名(3.2%);替奈普酶组796名患者中有122名(15.3%)在开始治疗后90天内死亡,阿替普酶组763名患者中有117名(15.4%)。

研究结果表明,对于所有符合溶栓标准的急性缺血性卒中患者,静脉注射替奈普酶是替代阿替普酶的合理选择。

附:英文原文

Title: Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trial

Author: Bijoy K Menon, Brian H Buck, Nishita Singh, Yan Deschaintre, Mohammed A Almekhlafi, Shelagh B Coutts, Sibi Thirunavukkarasu, Houman Khosravani, Ramana Appireddy, Francois Moreau, Gord Gubitz, Aleksander Tkach, Luciana Catanese, Dar Dowlatshahi, George Medvedev, Jennifer Mandzia, Aleksandra Pikula, Jai Shankar, Heather Williams, Thalia S Field, Alejandro Manosalva, Muzaffar Siddiqui, Atif Zafar, Oje Imoukhuede, Gary Hunter, Andrew M Demchuk, Sachin Mishra, Laura C Gioia, Shirin Jalini, Caroline Cayer, Stephen Phillips, Elsadig Elamin, Ashkan Shoamanesh, Suresh Subramaniam, Mahesh Kate, Gregory Jacquin, Marie-Christine Camden, Faysal Benali, Ibrahim Alhabli, Fouzi Bala, MacKenzie Horn, Grant Stotts, Michael D Hill, David J Gladstone, Alexandre Poppe, Arshia Sehgal, Qiao Zhang, Brendan Cord Lethebe, Craig Doram, Ayoola Ademola, Michel Shamy, Carol Kenney, Tolulope T Sajobi, Richard H Swartz, Abhilekh Srivastava, Ahmed M Aljammaz, Akintomide Femi Akindotun, Albert Y Jin, Alexander Fraser, Alexander V Khaw, Alexandru Lemnaru, Alisia Southwell, Alnar Ramji, Alonso Alvarado-Bolaos, Amr Mouminah, Amro B Lahlouh, Amy Y Yu, Anas Alrohimi, Andre Lavoie, Andrea Rogge, Andrew Micieli, Andrew Linh Nguyen, Angelique Callaghan-Brown, Anita Florendo-Cumbermack

Issue&Volume: 2022-06-29

Abstract:

Background

Intravenous 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.

Methods

In 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.

Findings

Between 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

Interpretation

Intravenous 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.

DOI: 10.1016/S0140-6736(22)01054-6

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)01054-6/fulltext

期刊信息

LANCET:《柳叶刀》,创刊于1823年。隶属于爱思唯尔出版社,最新IF:59.102
官方网址:http://www.thelancet.com/
投稿链接:http://ees.elsevier.com/thelancet

?