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™)
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Enrollment
- 3,602
- Locations
- 1
- Primary Endpoint
- Pharmacology Arm - Major Adverse Ischemic Cardiac Events and Major Bleeding Events
Study Overview
Brief Summary
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
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™).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Factorial
- Primary Purpose
- Treatment
- Masking
- Single (Participant)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
- •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.
Arms & Interventions
Pharmacology Arm
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.
Intervention: Bivalirudin (Drug)
Pharmacology Arm
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.
Intervention: Unfractionated heparin (Drug)
Stent Arm
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
Intervention: Bare metal stent (Device)
Stent Arm
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
Intervention: Paclitaxel-eluting stent (Device)
Outcomes
Primary Outcomes
Pharmacology Arm - Major Adverse Ischemic Cardiac Events and Major Bleeding Events
Time Frame: 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
Time Frame: 1 year
Number of Participants With Ischemic Target Lesion Revascularization
Stent Arm - Death, Reinfarction, Stroke, or Stent Thrombosis
Time Frame: 1 year
Number of Participants With Death, Reinfarction, Stroke, or Stent Thrombosis
Secondary Outcomes
- Pharmacology Arm - Non-Coronary Artery Bypass Grafting-Related Major Bleeding(30 days)
- Pharmacology Arm - Major Adverse Cardiovascular Events(3 years)
- Stent Arm - Segment Binary Angiographic Restenosis(13 months)