Background: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 w...Background: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.Methods: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.Results: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.Conclusion: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.Trial registration:www.ClinicalTrials.gov(No.NCT02835534).展开更多
基金supported by the Guangzhou Recomgen Biotech Co.,Ltd.The funder had no role in the design and conduct of the studycollection,management,analysis,and interpretation of the data
文摘Background: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.Methods: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.Results: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.Conclusion: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.Trial registration:www.ClinicalTrials.gov(No.NCT02835534).
