Trial to Compare the Efficacy and Safety of a Single Bolus of TNK-tPA (Tenecteplase, Metalyse®) With Accelerated Infusion of Rt-PA (Alteplase, Actilyse®) in Asian Patients With Acute Myocardial Infarction

A Randomised, Open-label, Multi-center, Angiographic Trial to Compare the Efficacy and Safety of Single Bolus of Tenecteplase (Metalyse®) With Accelerated Infusion of Alteplase in Asian Patients With Acute Myocardial Infarction

The objective of this trial was to compare the efficacy and safety of a single bolus of TNK-tPA (tenecteplase, Metalyse®) compared with rt-PA (alteplase, Actilyse®) in Asian patients.

Study Overview

• Status: Completed
• Conditions: Myocardial Infarction
• Intervention / Treatment: Drug: TNK-tPA; Drug: rt-PA

Detailed Description

This was a randomized (1:1), open-label, multi-center, active-control, parallel-group study to compare the efficacy and safety of TNK-tPA (tenecteplase, Metalyse®) with that of accelerated rt-PA (alteplase, Actilyse®) in Asian patients with AMI. The primary endpoint (TIMI 3 Flow) and the secondary endpoint (TIMI frame count) were evaluated in a blinded manner in the core laboratory.

Patients eligible for the trial who met all inclusion and exclusion criteria and who gave their informed consent were randomized to one of two treatment groups (i.e. TNK-tPA or accelerated rt-PA).

The study period totaled 30-37 days and included baseline, randomisation, study drug administration, in-hospital follow-up and thirty-day follow-up.

Coronary angiography was performed at 90 minutes after the start of study drug administration. 12-lead electrocardiograms (ECGs) were obtained before randomization, between 60 to 75 minutes and 180 ± 15 minutes after the start of study drug administration, and at hospital discharge.

If the patient showed rapid and progressive hemodynamic deterioration before 90 minutes, rescue PTCA or other appropriate interventions should be performed at the discretion of the treating physician.

Following the analysis of TIMI flow and frame count at each study center, the results were carefully recorded on the CRFs. This data was stored on a compact disk or a film and labeled with the subject's study I.D. number. It was then sent with the summary worksheets and ECGs to the Angiographic Core Laboratory located at the Leuven Coordinating Center (LCC) of the University Hospital Gasthuisberg (Leuven, Belgium) for central evaluations.

Study Hypothesis:

The null hypothesis tested was that there was no difference between the two treatment groups: TNK-tPA (Tenecteplase, Metalyse®) and accelerated rt-PA (Actilyse®), against the alternative that there was a difference.

Comparison(s):

The primary endpoint of the study was TIMI 3 flow at 90 minutes after start of thrombolytic therapy, angiograms were evaluated in a blinded manner in a core laboratory.

• Study Type: Interventional
• Enrollment: 270
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100050
    • Beijing Friendship Hospital
  • Beijing, China, 100050
    • Beijing Xuan Wu Hospital
  • Beijing, China, 100029
    • Beijing An Zhen Hospital
  • Beijing, China, 100044
    • Beijing University
  • Beijing, China, 100730
    • Bejing Tongren Hospital
  • Dalian, China, 116033
    • Center Hospital of Dalian
  • Jinan, China, 250013
    • Center Hospital of Jinan
  • Shanghai, China, 200032
    • Fudan University
  • Shenyang, China, 110015
    • People's Hospital of Liaoning Province
• Hong Kong
  • Hong Kong, Hong Kong
    • The University of Hong Kong, Cardiology Division
• Korea, Republic of
  • Jung-Ku, Korea, Republic of, 700711
    • Dongsan Medical Center
  • Kwang-Ju, Korea, Republic of, 501757
    • Chunnam University Hospital
  • Pusan, Korea, Republic of, 602715
    • Dong-A University Hospital
  • Seoul, Korea, Republic of, 100744
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 120752
    • Yonsei University Severance Hospital
  • Seoul, Korea, Republic of, 138736
    • Seoul Joongang Hospital
  • Suwon, Korea, Republic of, 443721
    • A-Jou University Hospital
  • Wonju, Korea, Republic of
    • Wonju Christian Hospital (Yonsei University Hosp)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age >= 18 and <= 75 years.
2. Asian origin.
3. Ischemic discomfort >= 30 minutes in duration.
4. Onset of acute myocardial infarction (AMI) symptoms within 6 hours prior to randomization.

5. A twelve lead electrocardiogram (ECG) with one of the following:

   • ST segment elevation >= 0.1 mV in two or more limb leads; or
   • >= 0.2 mV in two or more contiguous precordial leads indicative of AMI.
6. Ability to give informed consent.

Exclusion Criteria:

1. Previous coronary artery bypass grafting (CABG) surgery.
2. Cardiogenic shock (e.g. systolic blood pressure [SBP] < 90 mmHg).
3. Systolic blood pressure (SBP) >= 180 mmHg and/or diastolic blood pressure (DBP) >= 110 mmHg during current admission on one reliable measurement prior to randomization.
4. Inability to undergo cardiac catheterization.
5. Significant bleeding disorder either at present or within the past 6 months.
6. Major surgery, biopsy of a parenchymal organ, or significant trauma within 3 months.
7. Any minor head trauma and/or any other trauma that occurred after onset of current myocardial infarction.
8. Use of heparin, GPIIb/IIIa antagonists or other anticoagulants within the last 2 weeks.
9. Any known history of stroke or transient ischemic attack or central nervous system structural damage (i.e. neoplasm, aneurysm, intracranial surgery).
10. Prolonged cardiopulmonary resuscitation (> 10 minutes) within 2 weeks.
11. Pregnancy, lactation or parturition within the previous 30 days. Women of childbearing potential must have had a negative pregnancy test and must have used a medically accepted method of birth control (i.e. uterine device, surgical sterilisation, progestogens alone).
12. Previous treatment with TNK-tPA (tenecteplase).
13. Inability to follow protocol and comply with follow-up.
14. Drug abuse within the last year.
15. Participation in another clinical trial within the previous 30 days.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The percentage of patients with thrombolysis in myocardial infarction (TIMI) grade 3 flow in the infarct-related artery (IRA)	at 90 minutes after the start of thrombolytic treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety
Infarct-related artery patency	at 90 minutes
The percentage of subjects with ST-segment resolution	at 60 and 180 minutes
Mortality	30-days
The effects of TNK-tPA on coagulation and fibrinogenolysis (at selected clinical sites)

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim
• Investigators: Study Chair: Boehringer Ingelheim Study Coordinator, Boehringer Ingelheim Shanghai

Study record dates

Study Major Dates

• Study Start: March 1, 2001
• Study Completion: February 1, 2006

Study Registration Dates

• First Submitted: September 7, 2005
• First Submitted That Met QC Criteria: September 7, 2005
• First Posted (Estimate): September 8, 2005

Study Record Updates

• Last Update Posted (Estimate): October 29, 2013
• Last Update Submitted That Met QC Criteria: October 28, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tenecteplase
• Other Study ID Numbers: 1123.8