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

NCT ID: NCT02835534

Last Updated: 2022-05-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 818 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-31
• Study Completion Date: 2020-01-31

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.

Conditions

Acute ST Elevation Myocardial Infarction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

rhTNK-tPA

Intervention Type: DRUG

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

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.

Group Type: ACTIVE_COMPARATOR

alteplase

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Recombinant Human TNK Tissue-type Plasminogen Activator; rt-PA

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chinese Academy of Medical Sciences, Fuwai Hospital

OTHER

Sponsor Role: collaborator

Peking University

OTHER

Sponsor Role: collaborator

CSPC Mingfule Pharmaceutical (Guangzhou) Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shubin Qiaos, MD

Role: PRINCIPAL_INVESTIGATOR

Chinese Academy of Medical Sciences, Fuwai Hospital

Qin Yang, MD

Role: STUDY_DIRECTOR

CSPC Mingfule Pharmaceutical (Guangzhou) Co., Ltd.

Locations

Guangzhou Recomgen Biotech Co., Ltd.

Guangzhou, Guangdong, China

Countries

China

References

Zhao X, Zhu Y, Zhang Z, Tao G, Xu H, Cheng G, Gao W, Ma L, Qi L, Yan X, Wang H, Xia Q, Yang Y, Li W, Rong J, Wang L, Ding Y, Guo Q, Dang W, Yao C, Yang Q, Gao R, Wu Y, Qiao S. Tenecteplase versus alteplase in treatment of acute ST-segment elevation myocardial infarction: A randomized non-inferiority trial. Chin Med J (Engl). 2024 Feb 5;137(3):312-319. doi: 10.1097/CM9.0000000000002731. Epub 2023 Jun 2.

Reference Type: DERIVED

PMID: 37265385 (View on PubMed)

Wang HB, Ji P, Zhao XS, Xu H, Yan XY, Yang Q, Yao C, Gao RL, Wu YF, Qiao SB. 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. BMJ Open. 2017 Sep 18;7(9):e016838. doi: 10.1136/bmjopen-2017-016838.

Reference Type: DERIVED

PMID: 28928186 (View on PubMed)

Other Identifiers

CP-2015-01

Identifier Type: -

Identifier Source: org_study_id