| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
The medical condition for this clinical trial is Acute Myocardial Infarction (AMI). AMI is defined as death or necrosis of myocardial cells. It is a diagnosis at the end of the spectrum of myocardial ischemia or acute coronary syndromes.
The patients who suffer from AMI are a restricted subpopulation of patients undergoing primary percutaneous coronary intervention (PCI). |
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| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
The primary objectives of this trial are:
1. To establish the safety and efficacy of the use of bivalirudin in patients with acute myocardial infarction undergoing a primary angioplasty strategy.
2. To establish the safety and efficacy of the paclitaxel-eluting TAXUS stent.
The purposes of the paclitaxel-eluting TAXUS will be described in the medical device submission.
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| E.2.2 | Secondary objectives of the trial |
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| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Sub-Study 1 :
Inflammatory and Hemostatic Biomarker Sub-Study, (objectives : to prospectively assess the absolute and relative prognostic value of numerous inflammatory and hemostatic biomarkers measured at different time periods in patients with AM, To examine the temporal stability of numerous inflammatory and hemostatic biomarkers, To determine which biomarkers have specific prognostic utility, To examine the relationship of inflammatory biomarkers to future plaque progression)
Sub-Study 2 :
Intravascular Ultrasound Sub-study, (Objective : to compare the vascular responses between bare metal stents and drug-eluting stents in patients undergoing primary percutaneous coronary intervention in acute myocardial infarction) |
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| E.3 | Principal inclusion criteria |
The first randomization inclusion criteria are:
1. Subject is over 18 years of age.
2. Must have clinical symptoms consistent with AMI (e.g., angina or anginal equivalent) lasting >20 minutes but <12 hours duration. If the symptom duration at the time of evaluation is <1 hour, to rule out unstable angina, the symptoms must be unresponsive to nitroglycerin (i.e. ongoing) prior to signing the informed consent. Patients with symptom onset within 12 hours, in whom the symptoms lasted >1 hour but subsequently resolved may still be enrolled if the ECG at the time of the evaluation shows definite ongoing ST segment elevation.
3. ECG criteria: ST-segment elevation of > or equal to 1 mm in > or equal to 2 contiguous leads, or (presumably new) left bundle branch block, or true posterior MI with ST depression of > or equal to 1 mm in > or equal to 2 contiguous anterior leads.
4. Written informed consent provided.
The second randomisation inclusion criteria are:
1. At least one acute infarct artery target vessel is present in which: a) ALL hemodynamically significant lesions can be stented with study stents, and b) ALL such lesions have a visually estimated reference diameter ≥2.25 mm and ≤4.0 mm
2. Expected ability to deliver the stent(s) to all culprit lesions (absence of excessive proximal tortuosity or severe calcification).
3. Expected ability to fully expand the stent(s) at all culprit lesions (absence of marked calcification).
Please cross refer to page 18 of 82 of the protocole
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| E.4 | Principal exclusion criteria |
The first randomisation exlusion criteria:
1. The patient has a known hypersensitivity or contraindication to any of the following: Heparin, pork or pork products; Both abciximab and eptifibatide; Aspirin; Both Clopidogrel and ticlopidine; Bivalirudin; Paclitaxel or Taxol; The polymer components of the TAXUS stent (SIBS), Stainless steel; and/or, Contrast media (patients with documented sensitivity to contrast which can be effectively pre-medicated with steroids and diphenhydramine (e.g. rash) may be enrolled. Patients with true anaphylaxis to prior contrast media, however, should not be enrolled).
2. Prior administration of thrombolytic therapy, bivalirudin, GP IIb/IIIa inhibitors, low molecular weight heparin or fondaparinux for this admission. Patients receiving prior unfractionated heparin may be enrolled, and treated per randomization.
3. Current use of coumadin.
4. Systemic (intravenous) Paclitaxel or Taxol use within 12 months.
5. Female of childbearing potential unless a recent pregnancy test is negative, or who possibly plan to become pregnant any time after enrolment into this study
6. History of bleeding diathesis or known coagulopathy (including heparin-induced thrombocytopenia), or will refuse blood transfusions
7. History of intra-cerebral mass, aneurysm, arteriovenous malformation, or hemorrhagic stroke.
8. Stroke or transient ischemic attack within the past 6 months, or any permanent residual neurologic defect.
9. Gastrointestinal or genitourinary bleeding within the last 2 months, or major surgery within six weeks.
10. Recent history or known current platelet count <100,000 cells/mm3 or Hgb <10 g/dL (note: baseline labs do not have to be available prior to enrollment).
11. Extensive peripheral vascular disease such that emergent angiography and intervention in the opinion of the investigator is likely to be difficult or complicated.
12. An elective surgical procedure is planned that would necessitate interruption of Thienopyridines during the first six months post enrollment.
13. Non-cardiac co-morbid conditions are present with life expectancy <1 year or that may result in protocol non-compliance.
14. Patients who are actively participating in another drug or device investigational study which have not completed the primary endpoint follow-up period.
15. Previous enrollment in this trial.
The second randomisation exclusion criteria are:
1. One or more hemodynamically significant lesion(s) is present in the infarct vessel (or side branches) which can only undergo balloon angioplasty or cannot be stented with a study stent; i.e., do not meet the angiographic inclusion criteria for a study stent.
2. The presence of a bifurcation lesion in the infarct vessel which will definitely require the implantation of two stents for treatment.
3. Anticipated need for greater than 100mm of study stent length.
4. The infarct related artery is an unprotected left main segment.
5. Patients with significant multi-vessel disease or anatomical features otherwise unfavorable for angioplasty such that the patient will have a high likelihood of requiring bypass surgery prior to 30 days.
6. The culprit vessel or lesion cannot be identified.
Please cross refer to pages 19 of 82 of the protocole |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Pharmacology Arm:
The net clinical benefit endpoint is the composite of major adverse ischemic events and major bleeding (bleeding adjudicated as not related to Coronary Artery Bypass Grafting (CABG)).
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Information not present in EudraCT |
| E.6.7 | Pharmacodynamic | Information not present in EudraCT |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Information not present in EudraCT |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Information not present in EudraCT |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | Yes |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| two randomisations - first to drug and second to stent |
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| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 68 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Pre-defined stopping rules are set by the Data Safety Monitoring Board (DSMB) for: death and composite of death, re-infarction, stent thrombosis and stroke. If the bivalirudin is inferior to heparin or the drug eluting TAXUS™stent is inferior to uncoated Express™ stent, for this criteria based on a log-rank test, the study may be stopped. Any DSMB recommendations for the termination of the studywill be submitted in writing to the Executive Committee for consideration and final decision.
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 6 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 6 |
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