Clinical trial NCT00148460: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Myocardial Infarction
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2005-09-08
Enrollment: 270
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The percentage of patients with thrombolysis in myocardial infarction (TIMI) grade 3 flow in the infarct-related artery (IRA)
timeFrame: at 90 minutes after the start of thrombolytic treatment
Secondary outcomes:
measure: Infarct-related artery patency
timeFrame: at 90 minutes
measure: The percentage of subjects with ST-segment resolution
timeFrame: at 60 and 180 minutes
measure: Mortality
timeFrame: 30-days
measure: Safety
measure: The effects of TNK-tPA on coagulation and fibrinogenolysis (at selected clinical sites)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing An Zhen Hospital
city: Beijing
country: China
facility: Beijing University
city: Beijing
country: China
facility: Beijing Friendship Hospital
city: Beijing
country: China
facility: Beijing Xuan Wu Hospital
city: Beijing
country: China
facility: Bejing Tongren Hospital
city: Dalian
country: China
facility: Center Hospital of Dalian
city: Jinan
country: China
facility: Center Hospital of Jinan
city: Shanghai
country: China
facility: Fudan University
city: Shenyang
country: China
facility: People's Hospital of Liaoning Province
city: Hong Kong
country: Hong Kong
facility: The University of Hong Kong, Cardiology Division
city: Jung-Ku
country: Korea, Republic of
facility: Dongsan Medical Center
city: Kwang-Ju
country: Korea, Republic of
facility: Chunnam University Hospital
city: Pusan
country: Korea, Republic of
facility: Dong-A University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Yonsei University Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul Joongang Hospital
city: Suwon
country: Korea, Republic of
facility: A-Jou University Hospital
city: Wonju
country: Korea, Republic of
facility: Wonju Christian Hospital (Yonsei University Hosp)
Study officials:
affiliation: Boehringer Ingelheim Shanghai
name: Boehringer Ingelheim Study Coordinator
role: STUDY_CHAIR
References: