search
Back to results

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

Primary Purpose

Acute ST Elevation Myocardial Infarction

Status
Completed
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
rhTNK-tPA
alteplase
Sponsored by
Guangzhou Recomgen Biotech Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute ST Elevation Myocardial Infarction focused on measuring acute ST elevation myocardial infarction

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Guangzhou Recomgen Biotech Co., Ltd.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

rhTNK-tPA

rt-PA

Arm Description

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: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.

Outcomes

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)
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)
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
The in-hospital MACCE
The in-hospital and 30-day all-cause mortality
The in-hospital and 30-day cardiac deaths
The in-hospital recurrent MI
The 30-day revascularization
The in-hospital intracranial hemorrhage (ICH)
The in-hospital major GI bleeding events
The in-hospital total bleeding events

Full Information

First Posted
June 12, 2016
Last Updated
May 19, 2022
Sponsor
Guangzhou Recomgen Biotech Co., Ltd.
Collaborators
Chinese Academy of Medical Sciences, Fuwai Hospital, Peking University
search

1. Study Identification

Unique Protocol Identification Number
NCT02835534
Brief Title
The Efficacy and Safety of rhTNK-tPA in Comparison With Alteplase(Rt-PA) as Fibrinolytic Therapy of Acute STEMI
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
May 2016 (Actual)
Primary Completion Date
October 2019 (Actual)
Study Completion Date
January 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Guangzhou Recomgen Biotech Co., Ltd.
Collaborators
Chinese Academy of Medical Sciences, Fuwai Hospital, Peking University

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute ST Elevation Myocardial Infarction
Keywords
acute ST elevation myocardial infarction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
818 (Actual)

8. Arms, Groups, and Interventions

Arm Title
rhTNK-tPA
Arm Type
Experimental
Arm Description
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.
Arm Title
rt-PA
Arm Type
Active Comparator
Arm Description
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
Intervention Name(s)
rhTNK-tPA
Other Intervention Name(s)
Recombinant Human TNK Tissue-type Plasminogen Activator
Intervention Description
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
Intervention Name(s)
alteplase
Other Intervention Name(s)
rt-PA
Intervention Description
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 Measure Information:
Title
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)
Description
A patent IRA was defined as TIMI grade 2 or 3 flow on the angiogram
Time Frame
within 24 hours after therapy
Secondary Outcome Measure Information:
Title
The rate of MACCE (Major Adverse Cardiovascular and Cerebrovascular Events)
Description
MACCE composited of total death, non-fatal recurrent MI, non-fatal stroke (ischemic and Hemorrhage), PCI for failed reperfusion and PCI for reocclusion
Time Frame
within 30 days after the start of fibrinolytic therapy
Title
The rate of successful reperfusion with clinical evidences
Time Frame
within 24 hours of fibrinolytic therapy
Title
The in-hospital MACCE
Time Frame
during hospitalization (from the date of admission to the date of discharge, assessed up to 1 month)
Title
The in-hospital and 30-day all-cause mortality
Time Frame
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
Title
The in-hospital and 30-day cardiac deaths
Time Frame
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
Title
The in-hospital recurrent MI
Time Frame
during hospitalization (from the date of admission to the date of discharge, assessed up to 1 month)
Title
The 30-day revascularization
Time Frame
30 days after the start of therapy
Title
The in-hospital intracranial hemorrhage (ICH)
Time Frame
during hospitalization (from the date of admission to the date of discharge, assessed up to 1 month)
Title
The in-hospital major GI bleeding events
Time Frame
during hospitalization (from the date of admission to the date of discharge, assessed up to 1 month)
Title
The in-hospital total bleeding events
Time Frame
during hospitalization (from the date of admission to the date of discharge, assessed up to 1 month)
Other Pre-specified Outcome Measures:
Title
The frequency and severity of AEs
Time Frame
during hospitalization (from the date of admission to the date of discharge, assessed up to 1 month)
Title
Medical cost within the initial hospitalization
Time Frame
from the date of admission to the date of discharge, assessed up to 1 month
Title
The frequency of re-hospitalizations and emergency room visits
Time Frame
at 30 days after therapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shubin Qiaos, MD
Organizational Affiliation
Chinese Academy of Medical Sciences, Fuwai Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Qin Yang, MD
Organizational Affiliation
Guangzhou Recomgen Biotech Co., Ltd.
Official's Role
Study Director
Facility Information:
Facility Name
Guangzhou Recomgen Biotech Co., Ltd.
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510530
Country
China

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
28928186
Citation
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.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs