Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction

Phase 3

Completed

Conditions: Myocardial Infarction

Interventions: Device: Bare metal stent
Drug: Bivalirudin
Device: Paclitaxel-eluting stent
Drug: Unfractionated heparin

Registration Number: NCT00433966

Lead Sponsor: Cardiovascular Research Foundation, New York

Brief Summary: The primary objectives of the trial are:

1. 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.

2. 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: 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™).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 3602

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Stent Arm	Bare metal stent	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: 1. reduced rates of target lesion revascularization for ischemia at 1 year 2. similar rates of death, reinfarction, stroke or stent thrombosis at 1 year 3. lower rates of analysis segment binary angiographic restenosis at 13 months
Stent Arm	Paclitaxel-eluting stent	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: 1. reduced rates of target lesion revascularization for ischemia at 1 year 2. similar rates of death, reinfarction, stroke or stent thrombosis at 1 year 3. lower rates of analysis segment binary angiographic restenosis at 13 months
Pharmacology Arm	Bivalirudin	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: 1. reduced rates of major bleeding events at 30 days 2. similar rates of major adverse ischemic cardiac events at 30 days 3. reduced rates of the composite of major adverse ischemic cardiac events + major bleeding at 30 days.
Pharmacology Arm	Unfractionated heparin	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: 1. reduced rates of major bleeding events at 30 days 2. similar rates of major adverse ischemic cardiac events at 30 days 3. reduced rates of the composite of major adverse ischemic cardiac events + major bleeding at 30 days.

Primary Outcome Measures

Name	Time	Method
Pharmacology Arm - Major Adverse Ischemic Cardiac Events and Major Bleeding Events	30 Days	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).
Stent Arm - Ischemic Target Lesion Revascularization	1 year	Number of Participants With Ischemic Target Lesion Revascularization
Stent Arm - Death, Reinfarction, Stroke, or Stent Thrombosis	1 year	Number of Participants With Death, Reinfarction, Stroke, or Stent Thrombosis

Secondary Outcome Measures

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