首都医科大学北京天坛医院王拥军教授比较了替奈普酶与阿替普酶治疗急性缺血性脑血管事件的疗效与安全性。该研究于2023年2月9日发表在《柳叶刀》杂志上。

替奈普酶替代阿替普酶作为急性缺血性脑卒中患者首选的溶栓治疗方法越来越受到关注。该研究组旨在评估替奈普酶与阿替普酶对这些患者的非劣效性。

在这项多中心、前瞻性、开放标签、盲终点、随机对照、非劣效性试验中，研究组从中国53个中心招募符合标准静脉溶栓条件但不符合血管内取栓条件的急性缺血性卒中成人患者，并随机分配（1：1）接受静脉注射替奈普酶（0.25 mg/kg，最大剂量25mg）或静脉注射阿替普酶（0.9 mg/kg，最大剂量90mg）。参与者必须能够在中风后4.5小时内接受治疗，在入组前改良Rankin量表（mRS）评分不超过1，并且美国国立卫生研究院中风量表评分5 - 25分。

患者和治疗临床医生没有双盲分组，临床医生对治疗类型的结果进行了评估。主要疗效结局是在改良意向治疗人群（所有随机分配的接受溶栓治疗的参与者）中评估的90天mRS评分为0 - 1的参与者比例，风险比（RR）的非劣效性边界为0.937。主要安全性结局是36小时内出现症状性颅内出血，对所有接受研究药物的参与者进行评估，并进行安全性评估。

2021年6月12日至2022年5月29日，1430名参与者被随机分配，其中替奈普酶组716名，阿替普酶组714名。6名接受替奈普酶治疗的患者和7名接受阿替普酶治疗的患者没有接受相应治疗，5名接受替奈普酶治疗的患者和11名接受阿替普酶治疗的患者失去了90天的随访。在改良意向治疗人群中，替奈普酶组705例患者中有439例（62%）出现主要结局，阿替普酶组696例患者有405例（58%），RR为1.07。

RR的95%CI下限大于非劣效性边界。替奈普酶组711人中有15人（2%）在36小时内出现症状性颅内出血，阿替普酶组706人中有13人（2%），RR为1.18。替奈普酶组90天内死亡46人（7%），阿替普酶组35人（5%），RR为1.31。

研究结果表明，在符合标准静脉溶栓条件但不符合或拒绝血管内取栓的缺血性脑卒中患者中，替奈普酶的疗效不逊于阿替普酶。

附：英文原文

Title: Tenecteplase versus alteplase in acute ischaemic cerebrovascular events (TRACE-2): a phase 3, multicentre, open-label, randomised controlled, non-inferiority trial

Author: Yongjun Wang, Shuya Li, Yuesong Pan, Hao Li, Mark W Parsons, Bruce C V Campbell, Lee H Schwamm, Marc Fisher, Fengyuan Che, Hongguo Dai, Deyang Li, Runhui Li, Junhai Wang, Yilong Wang, Xingquan Zhao, Zixiao Li, Huaguang Zheng, Yunyun Xiong, Xia Meng, Runhui Li, Dong Wang, Yongjun Wang, Shengli Chen, Dan Deng, Hong Zhang, Junhai Wang, Huisheng Chen, Hongwei Zhang, Yiping Wu, Hong Liu, Guozhi Lu, Liandong Zhao, Runxiu Zhu, Ying Liu, Fei Yi, Jianhua Gao, Hongguo Dai, Junfang Hao, Fengyuan Che, Xueli Cai, Zhihui Duan, Hong Yu, Tongguo Wei, Yufeng Tang, Zhaolong Peng, Baochao Zhang, Yan Song, Xiaofei Chen, Yunlin Liu, Jing Liu, Deyang Li, Weili Zhao, Xiue Wei, Qian Xue, Xuewen Liu, Yi Yang, Chuansheng zhao, Jun Chen, Yi Sui, Guizhi Sheng, Yun Zhang, Junyan Liu, Lianhuan Zhang, Weiwei Wang, Zhiyong Guo, Hao Li, Renping Hu, Guofang Chen, Zhigang Liang, Junbin Chen, Lei Xia, Zhihua Long

Issue&Volume: 2023-02-09

Abstract:

Background

There is increasing interest in replacing alteplase with tenecteplase as the preferred thrombolytic treatment for patients with acute ischaemic stroke. We aimed to establish the non-inferiority of tenecteplase to alteplase for these patients.

Methods

In this multicentre, prospective, open-label, blinded-endpoint, randomised controlled, non-inferiority trial, adults with an acute ischaemic stroke who were eligible for standard intravenous thrombolysis but ineligible for endovascular thrombectomy were enrolled from 53 centres in China and randomly assigned (1:1) to receive intravenous tenecteplase (0·25 mg/kg, maximum dose of 25 mg) or intravenous alteplase (0·9 mg/kg, maximum dose of 90 mg). Participants had to be able to receive treatment within 4·5 h of stroke, have a modified Rankin Scale (mRS) score of no more than 1 before enrolment, and have a National Institutes of Health Stroke Scale score of 5–25. Patients and treating clinicians were not masked to group assignment; clinicians evaluating outcomes were masked to treatment type. The primary efficacy outcome was the proportion of participants who had a mRS score of 0–1 at 90 days, assessed in the modified intention-to-treat population (all randomly assigned participants who received the allocated thrombolytic), with a non-inferiority margin of 0·937 for the risk ratio (RR). The primary safety outcome was symptomatic intracranial haemorrhage within 36 h, assessed in all participants who received study drug and had a safety assessment available. The trial is registered with ClinicalTrials.gov, NCT04797013, and has been completed.

Findings

Between June 12, 2021, and May 29, 2022, 1430 participants were enrolled and randomly assigned to tenecteplase (n=716) or alteplase (n=714). Six patients assigned to tenecteplase and seven to alteplase did not receive study product, and five participants in the tenecteplase group and 11 in the alteplase group were lost to follow-up at 90 days. The primary outcome in the modified intention-to-treat population occurred in 439 (62%) of 705 in the tenecteplase group versus 405 (58%) of 696 in the alteplase group (RR 1·07, 95% CI 0·98–1·16). The lower limit of the RR's 95% CI was greater than the non-inferiority margin. Symptomatic intracranial haemorrhage within 36 h was observed in 15 (2%) of 711 in the tenecteplase group and 13 (2%) of 706 in the alteplase group (RR 1·18, 95% CI 0·56–2·50). Mortality within 90 days occurred in 46 (7%) individuals in the tenecteplase group versus 35 (5%) in the alteplase group (RR 1·31, 95% CI 0·86–2·01).

Interpretation

Tenecteplase was non-inferior to alteplase in people with ischaemic stroke who were eligible for standard intravenous thrombolytic but ineligible for or refused endovascular thrombectomy.

DOI: 10.1016/S0140-6736(22)02600-9

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)02600-9/fulltext