Recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) versus alteplase (rt-PA) as fibrinolytic therapy for acute ST-segment elevation myocardial infarction (China TNK STEMI): protocol for a randomised, controlled, non-inferiority trial

Abstract

Aim: 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.

Methods and analysis: 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.

Ethics and dissemination: 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.

Trial registration number: NCT02835534.

Keywords: China; Fibrinolysis; alteplase; myocardial infarction; recombinant human TNK tissue-type plasminogen activator.

Conflict of interest statement

Competing interests: Guangzhou Recomgen Biotech Co., Ltd sponsored the clinical study. HBW, PJ, XYY, CY and YFW were responsible for study design and data analysis at the Peking University Clinical Research Institute, without direct payment from Guangzhou Recomgen Biotech Co., Ltd. XSZ, HYX, RLG and SBQ were clinical investigators in this clinical trial, without direct payment from Guangzhou Recomgen Biotech Co., Ltd for their roles in conducting the study. QY is the employee of Guangzhou Recomgen Biotech Co., Ltd. Principal investigator has full access to the final trial data set, but the sponsor does not have access to the data.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1

Recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) therapeutic efficacy non-inferiority trial flow chart. IRA, infarct-related artery; MACCEs, major adverse cardiovascular and cerebrovascular events; PCI, percutaneous coronary intervention; p.o., orally; rt-PA, recombinant human tissue-type plasminogen activator.

Figure 2

Baseline evaluation, fibrinolytic therapy, and follow-up schedule. †Including past medical history and past therapeutic history. §Based on Killip class. ¶Blood routine examination, blood biochemistry, routine urine test and myocardial damage biomarker. ζBlood routine examination and myocardial damage biomarker. Ψ18 lead electrocardiogram (ECG) before fibrinolytic therapy; 12 lead ECG (18 lead ECG for posterior wall and right ventricular MI) examination repeated at 30, 60, 90 and 120 mins after fibrinolysis; when appropriate, ECG examination could be done at the discretion of the responsible physicians. ‡Detected at 10, 12, 14, 16, 18 and 24 hours after symptom onset, and on the second and third day after hospital admission. If available, cardiac troponin (cTn) will be collected at the time points. £Including mortality, non-fatal reinfarction, non-fatal stroke (both ischaemic and haemorrhagic stroke), percutaneous coronary intervention (PCI) due to thrombolysis failure and PCI due to reocclusion. ᶋHospital readmission and emergency department visiting due to cardiovascular disease. CK-MB, creatine kinase-MB; IRA, infarct-related artery; MACCEs, major adverse cardiovascular and cerebrovascular events.