Clinical trial NCT02835534: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Acute ST Elevation Myocardial Infarction
Keywords: acute ST elevation myocardial infarction
Lead sponsor: Guangzhou Recomgen Biotech Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Chinese Academy of Medical Sciences, Fuwai Hospital
name: Peking University
First posted: 2016-07-18
Enrollment: 818
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 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)
timeFrame: within 24 hours after therapy
Secondary outcomes:
measure: The rate of MACCE (Major Adverse Cardiovascular and Cerebrovascular Events)
timeFrame: within 30 days after the start of fibrinolytic therapy
measure: The rate of successful reperfusion with clinical evidences
timeFrame: within 24 hours of fibrinolytic therapy
measure: The in-hospital MACCE
timeFrame: during hospitalization (from the date of admission to the date of discharge, assessed up to 1 month)
measure: The in-hospital and 30-day all-cause mortality
timeFrame: 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
measure: The in-hospital and 30-day cardiac deaths
timeFrame: 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
measure: The in-hospital recurrent MI
timeFrame: during hospitalization (from the date of admission to the date of discharge, assessed up to 1 month)
measure: The 30-day revascularization
timeFrame: 30 days after the start of therapy
measure: The in-hospital intracranial hemorrhage (ICH)
timeFrame: during hospitalization (from the date of admission to the date of discharge, assessed up to 1 month)
measure: The in-hospital major GI bleeding events
timeFrame: during hospitalization (from the date of admission to the date of discharge, assessed up to 1 month)
measure: The in-hospital total bleeding events
timeFrame: during hospitalization (from the date of admission to the date of discharge, assessed up to 1 month)
Other outcomes:
measure: The frequency and severity of AEs
timeFrame: during hospitalization (from the date of admission to the date of discharge, assessed up to 1 month)
measure: Medical cost within the initial hospitalization
timeFrame: from the date of admission to the date of discharge, assessed up to 1 month
measure: The frequency of re-hospitalizations and emergency room visits
timeFrame: at 30 days after therapy
Locations:
city: Guangzhou
country: China
facility: Guangzhou Recomgen Biotech Co., Ltd.
state: Guangdong
Study officials:
affiliation: Chinese Academy of Medical Sciences, Fuwai Hospital
name: Shubin Qiaos, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Guangzhou Recomgen Biotech Co., Ltd.
name: Qin Yang, MD
role: STUDY_DIRECTOR
References:
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.