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

Myocardial Infarction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00148460
• Other study ID #: 1123.8
• Status: Completed
• Phase: Phase 3
• First received: September 7, 2005
• Last updated: October 28, 2013
• Start date: March 2001
• Est. completion date: February 2006

Study information

• Verified date: October 2013
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug AdministrationSouth Korea: Korea Food and Drug Administration (KFDA)Hong Kong: Department of Health
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 270
• Est. completion date: February 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction

Intervention

Drug:
• TNK-tPA

• rt-PA

Locations

Country	Name	City	State
China	Beijing An Zhen Hospital	Beijing
China	Beijing Friendship Hospital	Beijing
China	Beijing University	Beijing
China	Beijing Xuan Wu Hospital	Beijing
China	Bejing Tongren Hospital	Beijing
China	Center Hospital of Dalian	Dalian
China	Center Hospital of Jinan	Jinan
China	Fudan University	Shanghai
China	People's Hospital of Liaoning Province	Shenyang
Hong Kong	The University of Hong Kong, Cardiology Division	Hong Kong
Korea, Republic of	Dongsan Medical Center	Jung-Ku
Korea, Republic of	Chunnam University Hospital	Kwang-Ju
Korea, Republic of	Dong-A University Hospital	Pusan
Korea, Republic of	Seoul Joongang Hospital	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Yonsei University Severance Hospital	Seoul
Korea, Republic of	A-Jou University Hospital	Suwon
Korea, Republic of	Wonju Christian Hospital (Yonsei University Hosp)	Wonju

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

China,  Hong Kong,  Korea, Republic of, 

Outcome

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