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

February 9, 2007
July 21, 2014
March 2005
June 2008   (final data collection date for primary outcome measure)
  • 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
  • Composite of major adverse ischemic cardiac events + major bleeding at 30 days
  • Ischemic target lesion revascularization at 1 year
  • Composite rate of death, reinfarction, stroke or stent thrombosis at 1 year
Complete list of historical versions of study NCT00433966 on ClinicalTrials.gov Archive Site
  • 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).
  • Major bleeding events at 30 days
  • Major adverse ischemic cardiac events at 30 days
  • Analysis segment binary angiographic restenosis at 13 months
Not Provided
Not Provided
 
Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction
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™)

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.

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™).

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Myocardial Infarction
  • 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
  • Device: Bare metal stent
    Uncoated bare metal stent
    Other Name: EXPRESS2™
  • Device: Paclitaxel-eluting stent
    slow rate-release paclitaxel-eluting stent
    Other Name: TAXUS™
  • 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.
    Interventions:
    • Drug: Bivalirudin
    • Drug: Unfractionated heparin
  • 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
    Interventions:
    • Device: Bare metal stent
    • Device: Paclitaxel-eluting stent

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
3604
November 2010
June 2008   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00433966
HORIZONS AMI
Yes
Gregg W. Stone, MD, Cardiovascular Research Foundation
Cardiovascular Research Foundation, New York
  • Boston Scientific Corporation
  • The Medicines Company
Principal Investigator: Gregg W Stone, MD CardioVascular Research Foundation, Korea
Study Director: Roxana Mehran, MD CardioVascular Research Foundation, Korea
Cardiovascular Research Foundation, New York
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP