Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction

Myocardial Infarction Clinical Trial

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™)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00433966
• Other study ID #: HORIZONS AMI
• Status: Completed
• Phase: Phase 3
• First received: February 9, 2007
• Last updated: November 30, 2017
• Start date: March 2005
• Est. completion date: November 2010

Study information

• Verified date: November 2017
• Source: Cardiovascular Research Foundation, New York
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 3602
• Est. completion date: November 2010
• Est. primary completion date: June 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction

Intervention

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).
• Unfractionated heparin
60 U/kg of IV heparin, started as soon as possible (ideally in the emergency room).

Device:
• Bare metal stent
Uncoated bare metal stent
• Paclitaxel-eluting stent
slow rate-release paclitaxel-eluting stent

Locations

Country	Name	City	State
United States	LeBauer CV Research Foundation	Greensboro	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
Cardiovascular Research Foundation, New York	Boston Scientific Corporation, The Medicines Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacology Arm - Major Adverse Ischemic Cardiac Events and Major Bleeding Events	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).	30 Days
Primary	Stent Arm - Ischemic Target Lesion Revascularization	Number of Participants With Ischemic Target Lesion Revascularization	1 year
Primary	Stent Arm - Death, Reinfarction, Stroke, or Stent Thrombosis	Number of Participants With Death, Reinfarction, Stroke, or Stent Thrombosis	1 year
Secondary	Pharmacology Arm - Major Adverse Cardiovascular Events	Number of participants with major adverse cardiovascular events (death, reinfarction, target-vessel revascularization for ischemia, and stroke)	30 days
Secondary	Pharmacology Arm - Non-Coronary Artery Bypass Grafting-Related Major Bleeding	Number of participants with major bleeding (bleeding adjudicated as not related to coronary artery bypass grafting)	30 days
Secondary	Stent Arm - Segment Binary Angiographic Restenosis	Number of Participants With Segment Binary Angiographic Restenosis (13-month Angiographic Subset).	13 months
Secondary	Pharmacology Arm - Major Adverse Cardiovascular Events	Number of participants with major adverse cardiovascular events (death, reinfarction, target-vessel revascularization for ischemia, and stroke)	3 years