Wang Hai-Bo, Ji Ping, Zhao Xing-Shan, Xu Haiyan, Yan Xiao-Yan, Yang Qin, Yao Chen, Gao Run-Lin, Wu Yang-Feng, Qiao Shu-Bin
Peking University Clinical Research Institute, Beijing, China.
Shenzhen-Peking University-The Hongkong University of Science & Technology Medical Center, Shenzhen, China.
BMJ Open. 2017 Sep 18;7(9):e016838. doi: 10.1136/bmjopen-2017-016838.
To evaluate the efficacy and safety of recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) in lowering major adverse cardiovascular and cerebrovascular events (MACCEs) in Chinese acute ST-segment elevation myocardial infarction (STEMI) patients.
The study is designed as a multicentre, randomised, controlled non-inferiority phase IV trial with balanced randomisation (1:1) in patients with STEMI. The planned sample size is 6200 participants (or 3100 per arm). Participants with STEMI will be randomised to receive either rhTNK-tPA or alteplase (rt-PA), with stratification by research centre, age and the time from symptom onset to randomisation. All patients will receive concomitant antiplatelet and anticoagulant therapy before fibrinolytic therapy. The participants assigned to the intervention group will receive an intravenous bolus of 16 mg rhTNK-tPA, while those assigned to the control group will receive an intravenous bolus of 8 mg rt-PA followed by 42 mg infusion over 90 mins. Other medications can also be administered at the discretion of the cardiologists in charge. All participants will be followed up for the primary study endpoint, the occurrence of MACCEs within 30 days after fibrinolytic therapy, which is defined as all-cause mortality, non-fatal re-infarction, non-fatal stroke, percutaneous coronary intervention (PCI) due to thrombolysis failure, and PCI due to reocclusion. Both intention-to-treat and per-protocol analyses will be done for the primary analyses.
The study procedures and informed consent form were approved by all participating hospitals. The results will be disseminated in peer review journals and academic conferences. This multicentre randomised controlled trial will provide high-quality data about the efficacy and safety of rhTNK-tPA and, once approved, its easier use should help improve the application of reperfusion therapy and hence the treatment outcomes of STEMI patients.
NCT02835534.
评估重组人TNK组织型纤溶酶原激活剂（rhTNK-tPA）降低中国急性ST段抬高型心肌梗死（STEMI）患者主要不良心血管和脑血管事件（MACCEs）的疗效及安全性。
本研究设计为一项多中心、随机、对照的非劣效性IV期试验，对STEMI患者进行均衡随机分组（1:1）。计划样本量为6200名参与者（每组3100名）。STEMI患者将被随机分配接受rhTNK-tPA或阿替普酶（rt-PA）治疗，按研究中心、年龄以及症状发作至随机分组的时间进行分层。所有患者在溶栓治疗前均接受抗血小板和抗凝治疗。分配至干预组的参与者将静脉推注16mg rhTNK-tPA，而分配至对照组的参与者将静脉推注8mg rt-PA，随后在90分钟内输注42mg。其他药物也可由负责的心脏病专家酌情使用。所有参与者将接受随访，以观察主要研究终点，即溶栓治疗后30天内MACCEs的发生情况，其定义为全因死亡率、非致死性再梗死、非致死性卒中、因溶栓失败进行的经皮冠状动脉介入治疗（PCI）以及因再闭塞进行的PCI。主要分析将进行意向性分析和符合方案分析。
研究程序和知情同意书已获得所有参与医院的批准。研究结果将在同行评审期刊和学术会议上发表。这项多中心随机对照试验将提供关于rhTNK-tPA疗效和安全性的高质量数据，一旦获批，其更简便的使用应有助于改善再灌注治疗的应用，从而提高STEMI患者的治疗效果。
NCT02835534。
