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

Acute ST Elevation Myocardial Infarction Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02835534
• Other study ID #: CP-2015-01
• Status: Completed
• Phase: Phase 4
• Start date: May 2016
• Est. completion date: January 2020

Study information

• Verified date: May 2022
• Source: Guangzhou Recomgen Biotech Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 818
• Est. completion date: January 2020
• Est. primary completion date: October 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute ST Elevation Myocardial Infarction
• Infarction
• Myocardial Infarction
• ST Elevation Myocardial Infarction

Intervention

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.
• 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.

Locations

Country	Name	City	State
China	Guangzhou Recomgen Biotech Co., Ltd.	Guangzhou	Guangdong

Sponsors (3)

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

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	The frequency and severity of AEs		during hospitalization (from the date of admission to the date of discharge, assessed up to 1 month)
Other	Medical cost within the initial hospitalization		from the date of admission to the date of discharge, assessed up to 1 month
Other	The frequency of re-hospitalizations and emergency room visits		at 30 days after therapy
Primary	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	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
Secondary	The rate of successful reperfusion with clinical evidences		within 24 hours of fibrinolytic therapy
Secondary	The in-hospital MACCE		during hospitalization (from the date of admission to the date of discharge, assessed up to 1 month)
Secondary	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
Secondary	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
Secondary	The in-hospital recurrent MI		during hospitalization (from the date of admission to the date of discharge, assessed up to 1 month)
Secondary	The 30-day revascularization		30 days after the start of therapy
Secondary	The in-hospital intracranial hemorrhage (ICH)		during hospitalization (from the date of admission to the date of discharge, assessed up to 1 month)
Secondary	The in-hospital major GI bleeding events		during hospitalization (from the date of admission to the date of discharge, assessed up to 1 month)
Secondary	The in-hospital total bleeding events		during hospitalization (from the date of admission to the date of discharge, assessed up to 1 month)