The Efficacy and Safety of rhTNK-tPA in Comparison With Alteplase(Rt-PA) as Fibrinolytic Therapy of Acute STEMI

Study Overview
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Brief Summary
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This study is aiming to test the hypothesis that efficacy of rhTNK-tPA was not inferior to rt-PA with respect to the 30-day MACCE rates after fibrinolytic therapy for STEMI patients. It is a multicenter, randomized, open, parallel, active-controlled, non-inferiority trial.

Detailed Description
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The study includes screening and baseline, randomization & intervention, in-hospital visit, at 30±3 days visit after fibrinolytic therapy. Following an initial eligibility screening assessment, all eligible patients who have signed the informed consent will be randomly assigned by an interactive Web-based central system for fibrinolytic therapy with either rhTNK-tPA or rt-PA. The standard care should be given to all patients except for the study interventions. Prior to fibrinolytic administration, enoxaparin (30-mg intravenous) or Un- Fractionated Heparin (maximum 4000U, intravenous) should be administered, combined with antiplatelet therapy consisted of both clopidogrel and aspirin in a 300-mg loading dose followed by routine dosage. Successful reperfusion according to the clinical evidence (EKG) should be assessed after fibrinolytic therapy.TIMI flow should be assessed for those patients with 24 hours coronary angiography. MACCE and bleeding events should be followed up and documented during the study until 30 days after fibrinolytic therap. An independent adjudication committee will judge the major endpoint events.

Official Title
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The Efficacy and Safety of rhTNK-tPA in Comparison With Alteplase(Rt-PA) as Fibrinolytic Therapy of Acute ST Elevation Myocardial Infarction(STEMI): a Multi-center, Randomized, Open, Parallel, Non-inferiority, Active Controlled Trial

Conditions
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Acute ST Elevation Myocardial Infarction

Intervention / Treatment
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* Drug: rhTNK-tPA
* Drug: alteplase


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of acute STEMI（meet with both conditions）: Ischemic chest pain ≥30mins in duration ST elevation ≥0.1 mV in two or more limb ECG leads or ≥0.2 mV in two or more contiguous precordial leads Onset of continuous ischemic symptoms of STEMI ≤6 hours prior to randomisation Anticipated Delay to Performing Primary PCI >60mins，or time from hospital arrival to to balloon inflation >90mins Signed Informed consent received prior to participation the study Exclusion Criteria: Non-ST-segment-elevation myocardial infarction or unstable angina Reinfacrtion Cardiacgenic shock Suspected aortic dissection New left bundle branch block in ECG Absolute and relative contraindications for Fibrinolytic Therapy in STEMI(referred from 2015 China STEMI Management Guideline）： Severe uncontrolled hypertension (unresponsive to emergency Therapy,BPs > 180 mmHg and/or BPd > 110 mmHg) Any prior ICH,stroke with unknown cause, Ischemic stroke within 3 months Known structural cerebral vascular lesion, malignant intracranial neoplasm Active bleeding, or bleeding diathesis, active peptic ulcer Significant closed-head or facial trauma within 3 months Intracranial or intraspinal surgery within 2 months Recent internal bleeding within 4 weeks Major surgery within 3 weeks, or Traumatic Prolonged cardiopulmonary resuscitation (>10 minutes) Noncompressible vascular punctures within 2 weeks Current use of anticoagulant therapy Current or with a history of significant diseases： Damage to the central nervous system Severe renal or hepatic dysfunction, blood system diseases, Present with cardiac rupture evidence Acute pericarditis,Subacute bacterial endocarditis, Septic thrombophlebitis or occluded AV cannula at seriously infected site Malignancy High likelihood of left heart thrombus, e.g., mitral stenosis with atrial fibrillation Diabetic hemorrhagic retinopathy or other hemorrhagic ophthalmic conditions History of PCI or coronary artery bypass graft（CABG）within 1 month Administration of fibrinlytic therapy prior to participation Weight below 50 kg Known current histroy of fall-down accident Any other unfavourable conditions for participation： Known participation in other clinical trials Known to allergic to rhTNK-tPA or tPA or relevant vehicle Pregnancy or lactation Mental disorder Present with any unsuitable conditions for participation or completion of the study at the discretion of their treating physician

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rhTNK-tPA<br>rhTNK-tPA; Dose:16mg; Mode of admin: Single bolus Dose:50mg; Enoxaparin or unfractionated heparin for anticoagulant therapy, clopidogrel and aspirin for antiplatelet therapy before fibrinolytic therapy. | Drug: rhTNK-tPA<br>* Dose:16mg; Mode of admin: Single bolus Enoxaparin or unfractionated heparin for anticoagulant therapy, clopidogrel and aspirin for antiplatelet therapy before fibrinolytic therapy.<br>* Other names: Recombinant Human TNK Tissue-type Plasminogen Activator;|
| Active Comparator: rt-PA<br>Drug:alteplase;Dose:50mg; Mode of admin: administered as an 8-mg initial IV bolus followed by an infusion of 42 mg over the next 90 minutes Enoxaparin or unfractionated heparin for anticoagulant therapy, clopidogrel and aspirin for antiplatelet therapy before fibrinolytic therapy. | Drug: alteplase<br>* Dose:50mg; Mode of admin: administered as an 8-mg initial IV bolus followed by an infusion of 42 mg over the next 90 minutes Enoxaparin or unfractionated heparin for anticoagulant therapy, clopidogrel and aspirin for antiplatelet therapy before fibrinolytic therapy.<br>* Other names: rt-PA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients with TIMI grade 2 or 3 flow in the infarct-related artery after therapy (Limited to the subgroup for coronary angiography within 24 hours after therapy) | A patent IRA was defined as TIMI grade 2 or 3 flow on the angiogram | within 24 hours after therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rate of MACCE (Major Adverse Cardiovascular and Cerebrovascular Events) | MACCE composited of total death, non-fatal recurrent MI, non-fatal stroke (ischemic and Hemorrhage), PCI for failed reperfusion and PCI for reocclusion | within 30 days after the start of fibrinolytic therapy | 
| The rate of successful reperfusion with clinical evidences |  | within 24 hours of fibrinolytic therapy | 
| The in-hospital MACCE |  | during hospitalization (from the date of admission to the date of discharge, assessed up to 1 month) | 
| The in-hospital and 30-day all-cause mortality |  | during hospitalization (from the date of admission to the date of discharge, assessed up to 1 month) and 30 days after the start of study interventions | 
| The in-hospital and 30-day cardiac deaths |  | during hospitalization (from the date of admission to the date of discharge) and 30 days after the start of study interventions, assessed up to 1 month | 
| The in-hospital recurrent MI |  | during hospitalization (from the date of admission to the date of discharge, assessed up to 1 month) | 
| The 30-day revascularization |  | 30 days after the start of therapy | 
| The in-hospital intracranial hemorrhage (ICH) |  | during hospitalization (from the date of admission to the date of discharge, assessed up to 1 month) | 
| The in-hospital major GI bleeding events |  | during hospitalization (from the date of admission to the date of discharge, assessed up to 1 month) | 
| The in-hospital total bleeding events |  | during hospitalization (from the date of admission to the date of discharge, assessed up to 1 month) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute ST elevation myocardial infarction