Zhao Xingshan, Zhu Yidan, Zhang Zheng, Tao Guizhou, Xu Haiyan, Cheng Guanchang, Gao Wen, Ma Liping, Qi Liping, Yan Xiaoyan, Wang Haibo, Xia Qingde, Yang Yuwang, Li Wanke, Rong Juwen, Wang Limei, Ding Yutian, Guo Qiang, Dang Wanjun, Yao Chen, Yang Qin, Gao Runlin, Wu Yangfeng, Qiao Shubin
Department of Cardiology, Beijing Jishuitan Hospital, Capital Medical University, The Fourth Clinical Medical College of Peking University, Beijing 100035, China.
Peking University Clinical Research Institute, Peking University First Hospital, Beijing 100191, China.
Chin Med J (Engl). 2024 Feb 5;137(3):312-319. doi: 10.1097/CM9.0000000000002731. Epub 2023 Jun 2.
A phase II trial on recombinant human tenecteplase tissue-type plasminogen activator (rhTNK-tPA) has previously shown its preliminary efficacy in ST elevation myocardial infarction (STEMI) patients. This study was designed as a pivotal postmarketing trial to compare its efficacy and safety with rrecombinant human tissue-type plasminogen activator alteplase (rt-PA) in Chinese patients with STEMI.
In this multicenter, randomized, open-label, non-inferiority trial, patients with acute STEMI were randomly assigned (1:1) to receive an intravenous bolus of 16 mg rhTNK-tPA or an intravenous bolus of 8 mg rt-PA followed by an infusion of 42 mg in 90 min. The primary endpoint was recanalization defined by thrombolysis in myocardial infarction (TIMI) flow grade 2 or 3. The secondary endpoint was clinically justified recanalization. Other endpoints included 30-day major adverse cardiovascular and cerebrovascular events (MACCEs) and safety endpoints.
From July 2016 to September 2019, 767 eligible patients were randomly assigned to receive rhTNK-tPA ( n = 384) or rt-PA ( n = 383). Among them, 369 patients had coronary angiography data on TIMI flow, and 711 patients had data on clinically justified recanalization. Both used a -15% difference as the non-inferiority efficacy margin. In comparison to rt-PA, both the proportion of patients with TIMI grade 2 or 3 flow (78.3% [148/189] vs. 81.7% [147/180]; differences: -3.4%; 95% confidence interval [CI]: -11.5%, 4.8%) and clinically justified recanalization (85.4% [305/357] vs. 85.9% [304/354]; difference: -0.5%; 95% CI: -5.6%, 4.7%) in the rhTNK-tPA group were non-inferior. The occurrence of 30-day MACCEs (10.2% [39/384] vs. 11.0% [42/383]; hazard ratio: 0.96; 95% CI: 0.61, 1.50) did not differ significantly between groups. No safety outcomes significantly differed between groups.
rhTNK-tPA was non-inferior to rt-PA in the effect of improving recanalization of the infarct-related artery, a validated surrogate of clinical outcomes, among Chinese patients with acute STEMI.
www.ClinicalTrials.gov (No. NCT02835534).
一项关于重组人替奈普酶组织型纤溶酶原激活剂（rhTNK - tPA）的II期试验先前已显示其在ST段抬高型心肌梗死（STEMI）患者中的初步疗效。本研究旨在作为一项关键的上市后试验，比较其与重组人组织型纤溶酶原激活剂阿替普酶（rt - PA）在中国STEMI患者中的疗效和安全性。
在这项多中心、随机、开放标签、非劣效性试验中，急性STEMI患者被随机分配（1:1）接受静脉推注16 mg rhTNK - tPA或静脉推注8 mg rt - PA，随后在90分钟内输注42 mg。主要终点是根据心肌梗死溶栓（TIMI）血流分级2级或3级定义的再通。次要终点是临床合理的再通。其他终点包括30天主要不良心血管和脑血管事件（MACCEs）以及安全性终点。
2016年7月至2019年9月，767例符合条件的患者被随机分配接受rhTNK - tPA（n = 384）或rt - PA（n = 383）。其中，369例患者有TIMI血流的冠状动脉造影数据，711例患者有临床合理再通的数据。两者均采用-15%的差异作为非劣效性疗效界值。与rt - PA相比，rhTNK - tPA组中TIMI 2级或3级血流患者的比例（78.3% [148/189] 对81.7% [147/180]；差异：-3.4%；95%置信区间[CI]：-11.5%，4.8%）和临床合理再通的比例（85.4% [305/357] 对85.9% [304/354]；差异：-0.5%；95% CI：-5.6%，4.7%）均为非劣效。两组间30天MACCEs的发生率（10.2% [39/384] 对11.0% [42/383]；风险比：0.96；95% CI：0.61，1.50）无显著差异。两组间的安全性结果无显著差异。
在中国急性STEMI患者中，rhTNK - tPA在改善梗死相关动脉再通效果方面不劣于rt - PA，梗死相关动脉再通是临床结局的有效替代指标。
