Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction

Cardiovascular Research Foundation (CRF)

Status and phase: Completed; Phase 3

Conditions: Myocardial Infarction

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

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00433966

HORIZONS AMI

Details and patient eligibility

About

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.

Full 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™).

Enrollment: 3,602 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Single Blind

---

3,602 participants in 2 patient groups

Pharmacology Arm

Active Comparator group

Description:

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.

Treatment:

Drug: Unfractionated heparin

Drug: Bivalirudin

Stent Arm

Active Comparator group

Description:

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

Treatment:

Device: Bare metal stent

Device: Paclitaxel-eluting stent