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

Sponsor

Guangzhou Recomgen Biotech Co., Ltd. (Industry)

Overall Status

Completed

CT.gov ID

NCT02835534

Collaborator

Chinese Academy of Medical Sciences, Fuwai Hospital (Other), Peking University (Other)

818

Enrollment

Location

Arms

Actual Duration (Months)

18.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute ST Elevation Myocardial Infarction	Drug: rhTNK-tPA Drug: alteplase	Phase 4

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 Design

Study Type:

Interventional

Actual Enrollment :

818 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

May 1, 2016

Actual Primary Completion Date :

Oct 1, 2019

Actual Study Completion Date :

Jan 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: rhTNK-tPA Dose:16mg; Mode of admin: Single bolus Enoxaparin or unfractionated heparin for anticoagulant therapy, clopidogrel and aspirin for antiplatelet therapy before fibrinolytic therapy. Other Names: Recombinant Human TNK Tissue-type Plasminogen Activator
Active Comparator: rt-PA 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 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. Other Names: rt-PA

Arm

Intervention/Treatment

Experimental: 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.

Drug: rhTNK-tPA

Dose:16mg; Mode of admin: Single bolus Enoxaparin or unfractionated heparin for anticoagulant therapy, clopidogrel and aspirin for antiplatelet therapy before fibrinolytic therapy.

Other Names:

Recombinant Human TNK Tissue-type Plasminogen Activator

Active Comparator: rt-PA

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

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.

Other Names:

rt-PA

Outcome Measures

Primary Outcome Measures

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

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 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)]

Other Outcome Measures

The frequency and severity of AEs [during hospitalization (from the date of admission to the date of discharge, assessed up to 1 month)]
Medical cost within the initial hospitalization [from the date of admission to the date of discharge, assessed up to 1 month]
The frequency of re-hospitalizations and emergency room visits [at 30 days after therapy]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Guangzhou Recomgen Biotech Co., Ltd.	Guangzhou	Guangdong	China	510530

Sponsors and Collaborators

Guangzhou Recomgen Biotech Co., Ltd.
Chinese Academy of Medical Sciences, Fuwai Hospital
Peking University

Investigators

Principal Investigator: Shubin Qiaos, MD, Chinese Academy of Medical Sciences, Fuwai Hospital
Study Director: Qin Yang, MD, Guangzhou Recomgen Biotech Co., Ltd.