A dual arm factorial randomized trial in patients with ST segment elevation AMI to compare the results of using either anticoagulation with unfractionated heparin plus routine GP IIb/IIIa inhibition with bivalirubin and bail-out GP IIb/IIIa inhibition, and primary angioplasty with stent implantation with either a slow rate-release paclitaxel-eluting stent (TAXUS) or an otherwise identical uncoated bare metal stent (Express) - HORIZONS AMI Trial

Phase 1

Conditions: The medical condition for this clinical trial is Acute Myocardial Infarction (AMI). AMI is defined as death or necrosis of myocardial cells. It is a diagnosis at the end of the spectrum of myocardial ischemia or acute coronary syndromes. The patients who suffer from AMI are a restricted subpopulation of patients undergoing primary percutaneous coronary intervention (PCI).

Registration Number: EUCTR2005-001514-41-GB

Lead Sponsor: The Cardiovascular Research Foundation

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 3400

Inclusion Criteria

The first randomization inclusion criteria are:
1. Subject is over 18 years of age.
2. Must have clinical symptoms consistent with AMI (e.g., angina or anginal equivalent) lasting >20 minutes but <12 hours duration. If the symptom duration at the time of evaluation is <1 hour, to rule out unstable angina, the symptoms must be unresponsive to nitroglycerin (i.e. ongoing) prior to signing the informed consent. Patients with symptom onset within 12 hours, in whom the symptoms lasted >1 hour but subsequently resolved may still be enrolled if the ECG at the time of the evaluation shows definite ongoing ST segment elevation.
3. ECG criteria: ST-segment elevation of > or equal to 1 mm in > or equal to 2 contiguous leads, or (presumably new) left bundle branch block, or true posterior MI with ST depression of > or equal to 1 mm in > or equal to 2 contiguous anterior leads.
4. Written informed consent provided.

The second randomisation inclusion criteria are:
1. At least one acute infarct artery target vessel is present in which:a) ALL hemodynamically significant lesions can be stented with study stents, and b) ALL such lesions have a visually estimated reference diameter =2.25 mm and =4.0 mm
2. Expected ability to deliver the stent(s) to all culprit lesions (absence of excessive proximal tortuosity or severe calcification).
3. Expected ability to fully expand the stent(s) at all culprit lesions (absence of marked calcification).

Please cross refer to page 18 of 82 of the protocole

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

The first randomisation exlusion criteria:
1. The patient has a known hypersensitivity or contraindication to any of the following: 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 (patients with documented sensitivity to contrast which can be effectively pre-medicated with steroids and diphenhydramine (e.g. rash) may be enrolled. Patients with true anaphylaxis to prior contrast media, however, should not be enrolled).
2. 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.
3. Current use of coumadin.
4. Systemic (intravenous) Paclitaxel or Taxol use within 12 months.
5. Female of childbearing potential unless a recent pregnancy test is negative, or who possibly plan to become pregnant any time after enrolment into this study
6. History of bleeding diathesis or known coagulopathy (including heparin-induced thrombocytopenia), or will refuse blood transfusions
7. History of intra-cerebral mass, aneurysm, arteriovenous malformation, or hemorrhagic stroke.
8. Stroke or transient ischemic attack within the past 6 months, or any permanent residual neurologic defect.
9. Gastrointestinal or genitourinary bleeding within the last 2 months, or major surgery within six weeks.
10. Recent history or known current platelet count <100,000 cells/mm3 or Hgb <10 g/dL (note: baseline labs do not have to be available prior to enrollment).
11. Extensive peripheral vascular disease such that emergent angiography and intervention in the opinion of the investigator is likely to be difficult or complicated.
12. An elective surgical procedure is planned that would necessitate interruption of Thienopyridines during the first six months post enrollment.
13. Non-cardiac co-morbid conditions are present with life expectancy <1 year or that may result in protocol non-compliance.
14. Patients who are actively participating in another drug or device investigational study which have not completed the primary endpoint follow-up period.
15. Previous enrollment in this trial.

The second randomisation exclusion criteria are:
1. One or more hemodynamically significant lesion(s) is present in the infarct vessel (or side branches) which can only undergo balloon angioplasty or cannot be stented with a study stent; i.e., do not meet the angiographic inclusion criteria for a study stent.
2. The presence of a bifurcation lesion in the infarct vessel which will definitely require the implantation of two stents for treatment.
3. Anticipated need for greater than 100mm of study stent length.
4. The infarct related artery is an unprotected left main segment.
5. Patients with significant multi-vessel disease or anatomical features otherwise unfavorable for angioplasty such that the patient will have a high likelihood of requiring bypass surgery prior to 30 days.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Secondary Objective: Not applicable;<br> Primary end point(s): Pharmacology Arm:<br> The net clinical benefit endpoint is the composite of major adverse ischemic events and major bleeding (bleeding adjudicated as not related to Coronary Artery Bypass Grafting (CABG)).<br> ;<br> Main Objective: The primary objectives of this trial are:<br> 1. To establish the safety and efficacy of the use of bivalirudin in patients with acute myocardial infarction undergoing a primary angioplasty strategy.<br> 2. To establish the safety and efficacy of the paclitaxel-eluting TAXUS stent.<br><br> The purposes of the paclitaxel-eluting TAXUS will be described in the medical device submission.<br>

Secondary Outcome Measures

Name	Time	Method