A Study to Investigate the Procoagulant Effect of Tenecteplase (TNK-tPA), Alteplase (Rt-PA) and Streptokinase (SK) Administered to Patients With Acute Myocardial Infarction (AMI)

Study Overview
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Brief Summary
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Primary objective: to evaluate the procoagulant effect of TNK-tPA compared to rt-PA and streptokinase, administered to patients with AMI, by measuring the concentration of TAT at 2 hours after the start of treatment versus baseline values. Secondary objective: change from baseline in concentration of TAT at 6 and 24 hours; change from baseline in concentration of D-dimers, F1+2, PAI-1, PAP at 2, 6 and 24 hours. Incidence of adverse events (AE's), in -hospital complications, major or minor bleedings and serious adverse events.

Official Title
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An Open-label, Randomised, Parallel-group Comparison to Investigate the Procoagulant Effect of Tenecteplase (TNK-tPA), Alteplase (Rt-PA) and Streptokinase (SK) Administered to Patients With AMI

Conditions
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Myocardial Infarction

Intervention / Treatment
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* Drug: Tenecteplase
* Drug: Alteplase
* Drug: Streptokinase


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Onset of symptoms of AMI within 6 hours from randomisation A twelve-lead electrocardiogram (ECG) showing ST-segment elevation ≥ 0.1 millivolt (mV) in two or more limb leads, or ≥ 0.2 mV in two or more contiguous precordial leads indicative of AMI, or new left bundle-branch block Age ≥ 18 Exclusion Criteria: Hypertension defined as blood pressure > 180/110 mmHg (systolic BP > 180 mmHg and/or diastolic BP > 110 mmHg) on repeated measurements during current admission prior to randomisation Use of abciximab (ReoPro®) within the preceding 7 days or eptifibatide (Integrilin®) or tirofiban (aggrastat®) within the past 48 hours Use of heparin within the preceding 12 hours Current therapeutic oral anticoagulation Major surgery, biopsy of a parenchymal organ, or significant trauma within 2 months Any minor head trauma and any other trauma occurring after the onset of the current myocardial infarction Any known history of stroke or transient ischemic attack or dementia Any known structural damage of the central nervous system Ruptured aortic aneurism Active bleeding Prolonged cardiopulmonary resuscitation (> 10 minutes) in the previous two weeks Pregnancy or lactation, parturition within the previous 30 days. Women of childbearing potential must have a negative pregnancy test Any known active participation in another investigative drug study or device protocol in the past 30 days Previous enrolment in this study Any other condition that the investigator feels would place the patient at increased risk if the investigational therapy were initiated Inability to follow the protocol and comply with follow-up requirements

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tenecteplase<br>Single i.v. bolus followed by infusion, weight adjusted | Drug: Tenecteplase<br> <br> |
| Active Comparator: Alteplase<br>Single i.v. bolus followed by infusion | Drug: Alteplase<br> <br> |
| Active Comparator: Streptokinase<br>I.V. infusion | Drug: Streptokinase<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline in concentration of thrombin anti-thrombin complex (TAT) |  | Baseline, 2 hours after start of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline in TAT |  | Baseline, 6 and 24 hours after start of treatment | 
| Changes from baseline in D-dimers |  | Baseline, 2, 6 and 24 hours after start of treatment | 
| Changes from baseline in prothrombin fragments 1+2 (F1+F2) |  | Baseline, 2, 6 and 24 hours after start of treatment | 
| Changes from baseline in plasminogen-activator inhibitor-1 (PAI-1) |  | Baseline, 2, 6 and 24 hours after start of treatment | 
| Changes from baseline in plasmin-antiplasmin complex (PAP) |  | Baseline, 2, 6 and 24 hours after start of treatment | 
| Occurrence of adverse events (AE's) |  | Up to 30 days | 
| Occurrence of major bleedings |  | Up to 30 days | 
| Occurrence of minor bleedings |  | Up to 30 days | 
| Occurrence of serious adverse events (SAE's) |  | Up to 30 days | 
| Occurrence of in-hospital complications |  | Start of treatment until discharge from hospital |