Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction

Study Overview
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Brief Summary
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The primary objectives of the trial are: To establish the safety and efficacy of the use of bivalirudin (+ bail-out GP IIb/IIIa inhibitors) compared to the use of unfractionated heparin + GP IIb/IIIa inhibitors in patients with acute myocardial infarction undergoing a primary angioplasty strategy. To establish the safety and efficacy of the slow rate release paclitaxel-eluting TAXUS™ stent compared to an otherwise identical uncoated bare metal EXPRESS2™ stent.

Detailed Description
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Prospective, 2 x 2 factorial single blind, randomized, multi-center trial of 3400 patients enrolled at up to 200 centers. Patients will be randomized 1:1 in the emergency room to a) anticoagulation with unfractionated heparin plus routine GP IIb/IIIa inhibition vs. b) bivalirudin and bail-out GP IIb/IIIa inhibition. Following angiography, patients with lesions eligible for stenting will then undergo a second randomization (3:1) to stent implantation with either a) a slow rate-release paclitaxel-eluting stent (TAXUS™) or b) an otherwise identical uncoated bare metal stent (EXPRESS2™).

Official Title
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Dual Arm Factorial Randomized Trial in Patients w/ST Segment Elevation AMI to Compare the Results of Using Anticoagulation With Either Unfractionated Heparin + Routine GP IIb/IIIa Inhibition or Bivalirudin + Bail-out GP IIb/IIIa Inhibition; and Primary Angioplasty With Stent Implantation With Either a Slow Rate-release Paclitaxel-eluting Stent (TAXUS™) or Uncoated Bare Metal Stent (EXPRESS2™)

Conditions
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Myocardial Infarction

Intervention / Treatment
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* Drug: Bivalirudin
* Drug: Unfractionated heparin
* Device: Bare metal stent
* Device: Paclitaxel-eluting stent


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have clinical symptoms consistent with AMI (e.g., angina or anginal equivalent)lasting >20 minutes but <12 hours in duration; ST-segment elevation of >1 mm in >2 contiguous leads, or (presumably new) left bundle branch block, or true posterior MI with ST depression of >1 mm in >2 contiguous anterior leads; The patient or guardian agrees to the study protocol and the schedule of clinical and angiographic follow-up, and provides informed, written consent. Exclusion Criteria: The patient has a known hypersensitivity or contraindication to any of the following medications: 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; 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; Current use of coumadin; Systemic (intravenous) Paclitaxel or Taxol use within 12 months; Female of childbearing potential, unless a recent pregnancy test is negative, who possibly plans to become pregnant any time after enrollment into this study; History of bleeding diathesis or known coagulopathy (including heparin-induced thrombocytopenia), or will refuse blood transfusions; History of intra-cerebral mass, aneurysm, arteriovenous malformation, or hemorrhagic stroke; Stroke or transient ischemic attack within the past 6 months, or any permanent residual neurologic defect; Gastrointestinal or genitourinary bleeding within the last 2 months, or major surgery within six weeks; Recent history or known current platelet count <100,000 cells/mm3 or Hgb <10 g/dL; Extensive peripheral vascular disease, such that emergent angiography and intervention in the opinion of the investigator is likely to be difficult or complicated; An elective surgical procedure is planned that would necessitate interruption of thienopyridines during the first six months post enrollment; Non-cardiac co-morbid conditions are present with life expectancy <1 year or that may result in protocol non-compliance; Patients who are actively participating in another drug or device investigational study, which have not completed the primary endpoint follow-up period; Previous enrollment in this trial; Patients who underwent coronary stent implantation within the past 30 days.

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: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pharmacology Arm<br>To establish the safety and efficacy of the use of bivalirudin in patients with acute myocardial infarction undergoing a primary angioplasty strategy by showing that compared to unfractionated heparin plus routine use of GP IIb/IIIa inhibitors, bivalirudin (with use of GP IIb/IIIa inhibitors reserved for angioplasty complications) results in: reduced rates of major bleeding events at 30 days similar rates of major adverse ischemic cardiac events at 30 days reduced rates of the composite of major adverse ischemic cardiac events + major bleeding at 30 days. | Drug: Bivalirudin<br>* Bivalirudin bolus of 0.75 mg/kg IV, followed by an infusion of 1.75 mg/kg/h as soon as logistically feasible (ideally in the emergency room).<br>* Other names: Angiomax;Drug: Unfractionated heparin<br>* 60 U/kg of IV heparin, started as soon as possible (ideally in the emergency room).<br>* Other names: Heparin Sodium;|
| Active Comparator: Stent Arm<br>To establish the safety and efficacy of the paclitaxel-eluting TAXUS™ stent by showing that compared to an otherwise identical bare metal EXPRESS2™ stent, the TAXUS™ stent results in: reduced rates of target lesion revascularization for ischemia at 1 year similar rates of death, reinfarction, stroke or stent thrombosis at 1 year lower rates of analysis segment binary angiographic restenosis at 13 months | Device: Bare metal stent<br>* Uncoated bare metal stent<br>* Other names: EXPRESS2™;Device: Paclitaxel-eluting stent<br>* slow rate-release paclitaxel-eluting stent<br>* Other names: TAXUS™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacology Arm - Major Adverse Ischemic Cardiac Events and Major Bleeding Events | Number of participants with major adverse cardiovascular events (death, reinfarction, target-vessel revascularization for ischemia, and stroke) and major bleeding (bleeding adjudicated as not related to coronary artery bypass grafting). | 30 Days | 
| Stent Arm - Ischemic Target Lesion Revascularization | Number of Participants With Ischemic Target Lesion Revascularization | 1 year | 
| Stent Arm - Death, Reinfarction, Stroke, or Stent Thrombosis | Number of Participants With Death, Reinfarction, Stroke, or Stent Thrombosis | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacology Arm - Major Adverse Cardiovascular Events | Number of participants with major adverse cardiovascular events (death, reinfarction, target-vessel revascularization for ischemia, and stroke) | 30 days | 
| Pharmacology Arm - Non-Coronary Artery Bypass Grafting-Related Major Bleeding | Number of participants with major bleeding (bleeding adjudicated as not related to coronary artery bypass grafting) | 30 days | 
| Stent Arm - Segment Binary Angiographic Restenosis | Number of Participants With Segment Binary Angiographic Restenosis (13-month Angiographic Subset). | 13 months | 
| Pharmacology Arm - Major Adverse Cardiovascular Events | Number of participants with major adverse cardiovascular events (death, reinfarction, target-vessel revascularization for ischemia, and stroke) | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myocardial Infarction, Angioplasty, Myocardial Ischemia, Myocardial Reperfusion, Stents, Heart Disease