Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction

This study has been completed.
Sponsor:
Collaborators:
Boston Scientific Corporation
The Medicines Company
Information provided by:
Cardiovascular Research Foundation, New York
ClinicalTrials.gov Identifier:
NCT00433966
First received: February 9, 2007
Last updated: July 21, 2014
Last verified: July 2014
  Purpose

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.

Condition Intervention Phase
Myocardial Infarction
Drug: Bivalirudin
Drug: Unfractionated heparin
Device: Bare metal stent
Device: Paclitaxel-eluting stent
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: 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™)

Resource links provided by NLM:


Further study details as provided by Cardiovascular Research Foundation, New York:

Primary Outcome Measures:
  • Pharmacology Arm - Primary [ Time Frame: 30 Days ] [ Designated as safety issue: Yes ]
    Composite of major adverse ischemic cardiac events and major bleeding (bleeding adjudicated as not related to CABG) = Composite net clinical benefit endpoint.

  • Stent Arm - Primary Efficacy [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Ischemic target lesion revascularization

  • Stent Arm - Primary Safety [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Composite rate of death, reinfarction, stroke or stent thrombosis


Secondary Outcome Measures:
  • Pharmacology Arm - Major Secondary [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
    Major adverse ischemic events (death, reinfarction, stroke or ischemic target vessel revascularization).

  • Pharmacology Arm - Major Secondary [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
    Major bleeding

  • Stent Arm - Major Secondary [ Time Frame: 13 months ] [ Designated as safety issue: Yes ]
    Analysis segment binary angiographic restenosis (13 month angiographic subset).


Enrollment: 3604
Study Start Date: March 2005
Study Completion Date: November 2010
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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:

  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.
Drug: Bivalirudin
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).
Other Name: Angiomax
Drug: Unfractionated heparin
60 U/kg of IV heparin, started as soon as possible (ideally in the emergency room).
Other Name: Heparin Sodium
Active Comparator: 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:

  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
Device: Bare metal stent
Uncoated bare metal stent
Other Name: EXPRESS2™
Device: Paclitaxel-eluting stent
slow rate-release paclitaxel-eluting stent
Other Name: TAXUS™

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™).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00433966

Locations
United States, North Carolina
LeBauer CV Research Foundation
Greensboro, North Carolina, United States, 27401
Sponsors and Collaborators
Cardiovascular Research Foundation, New York
Boston Scientific Corporation
The Medicines Company
Investigators
Principal Investigator: Gregg W Stone, MD CardioVascular Research Foundation, Korea
Study Director: Roxana Mehran, MD CardioVascular Research Foundation, Korea
  More Information

No publications provided by Cardiovascular Research Foundation, New York

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Gregg W. Stone, MD, Cardiovascular Research Foundation
ClinicalTrials.gov Identifier: NCT00433966     History of Changes
Other Study ID Numbers: HORIZONS AMI
Study First Received: February 9, 2007
Last Updated: July 21, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Cardiovascular Research Foundation, New York:
Myocardial Infarction
Angioplasty
Myocardial Ischemia
Myocardial Reperfusion
Stents
Heart Disease

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Paclitaxel
Calcium heparin
Bivalirudin
Heparin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Anticoagulants
Hematologic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Cardiovascular Agents
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on October 01, 2014