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

Phase 4

Completed

• Conditions: Acute ST Elevation Myocardial Infarction
• Interventions: Drug: rhTNK-tPA; Drug: alteplase

• Registration Number: NCT02835534
• Lead Sponsor: Guangzhou Recomgen Biotech Co., Ltd.

Brief Summary

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

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.

Study Timeline

• Study Start: 2016-05
• Study First Submitted: 2016-06-12
• Study First Submitted QC: 2016-07-13
• Study First Posted: 2016-07-18
• Primary Completion: 2019-10
• Study Completion: 2020-01
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-19
• Last Update Posted: 2022-05-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 818

Inclusion Criteria

1. 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

2. Onset of continuous ischemic symptoms of STEMI ≤6 hours prior to randomisation

3. Anticipated Delay to Performing Primary PCI >60mins，or time from hospital arrival to to balloon inflation >90mins

4. Signed Informed consent received prior to participation the study

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Exclusion Criteria

1. Non-ST-segment-elevation myocardial infarction or unstable angina

2. Reinfacrtion

3. Cardiacgenic shock

4. Suspected aortic dissection

5. New left bundle branch block in ECG

6. 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

7. 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

8. Administration of fibrinlytic therapy prior to participation

9. Weight below 50 kg

10. Known current histroy of fall-down accident

11. 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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
rhTNK-tPA	rhTNK-tPA	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.
rt-PA	alteplase	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.

Primary Outcome Measures

Name	Time	Method
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)	within 24 hours after therapy	A patent IRA was defined as TIMI grade 2 or 3 flow on the angiogram

Secondary Outcome Measures

Name	Time	Method
The rate of MACCE (Major Adverse Cardiovascular and Cerebrovascular Events)	within 30 days after the start of fibrinolytic therapy	MACCE composited of total death, non-fatal recurrent MI, non-fatal stroke (ischemic and Hemorrhage), PCI for failed reperfusion and PCI for reocclusion
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 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 recurrent MI	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)
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 major GI bleeding events	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)

Trial Locations

Locations (1)

Guangzhou Recomgen Biotech Co., Ltd.; 🇨🇳 Guangzhou, Guangdong, China