The purpose of this study is to show that, when compared with heparin (enoxaparin or unfractionated heparin) and routine GPIIb/IIIa inhibition (either started upfront or at the time of percutaneous coronary intervention [PCI]; Arm A):

1) Bivalirudin with routine GPIIb/IIIa inhibition (either started upfront or at the time of PCI; Arm B) provides non-inferior or superior overall clinical outcomes and

2) Bivalirudin alone (Arm C) reduces clinically significant bleeding. An important secondary objective for this comparison is to show that bivalirudin is not inferior for ischemic complications.

Condition	Treatment or Intervention	Phase
Unstable Angina Myocardial Infarction Acute Disease	Drug: Angiomax (bivalirudin) anticoagulant	Phase III

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

1. Be aged >=18 years at the time of randomization.

2. Have symptoms which include at least 10 minutes of angina or anginal equivalent that the investigator believes has a high likelihood of being ischemic in origin within the 24 hours prior to randomization consistent with a diagnosis of Unstable Angina/Non-ST Elevation Myocardial Infarction (UA/NSTEMI) (patients with symptoms atypical for cardiac ischemia should not be enrolled).

3. Meet at least one of the following criteria for UA/NSTEMI:

a) All of the following four features: *Age >= to 65 years; *aspirin taken within the last 7 days; *two or more episodes of angina in the last 24 hours; *three or more of the following risk factors: hypertension, high cholesterol, family history, diabetes, current smoker OR

b) ECG changes: New or presumably new ST-segment depression >=0.1 MV (>=1mm), or transient (<30 minutes) ST-segment elevation >=0.1MV (>=1mm) in at least 2 contiguous leads, OR

c) Abnormal cardiac enzymes within the 24 hours before enrollment defined as elevated troponin I, T or creatine phosphokinase-MB isoenzyme (CPK-MB) level greater than the site's upper limit of normal (ULN) OR

d) History of coronary artery disease with documentation of one of the following: *prior angiography (coronary stenosis of >50%); *prior PCI or Coronary Arterty Bypass Grafting (CABG); *prior definite, documented myocardial infarction.

4. Provide written informed consent before initiation of any study related procedures.

Exclusion Criteria:

1. Anticipated inability to perform angiography within 72 hours of randomization and anticipated inability to perform any intervention required (PCI or CABG) within the index hospitalization.

2. ST segment elevation of >1 mm in 2 contiguous ECG leads lasting for >30 minutes, or new left bundle branch block, or a clinical syndrome consistent with acute evolving transmural MI requiring immediate thrombolytic or interventional reperfusion therapy.

3. Cardiogenic shock (systolic blood pressure <80 mmHg for >30 minutes not responding to intravenous fluids, or requiring intravenous pressor agents or an intra-aortic balloon pump).

4. Bleeding diathesis or any history of hemorrhagic stroke or other intra-cerebral bleed, cerebral arteriovenous malformation, cerebral aneurysm or prior ischemic stroke within the last 2 years, or any prior stroke with residual neurologic deficit. Gastrointestinal or genitourinary bleeding within the last 2-weeks.

5. Platelet count <100,000 cells/mm3 at baseline, or history of heparin induced thrombocytopenia

6. Patients on warfarin or phenprocoumon, unless they can be safely discontinued and the baseline INR is < 1.5 times control.

7. Allergy to pork or pork products.

8. Patients who have been started on and received 2 or more doses of low molecular weight heparin for the current admission prior to randomization (patients who have received one dose of low molecular weight heparin may still be enrolled.

9. Patients who have been started on bivalirudin in the 6 hours prior to randomization

10. Thrombolytic therapy or abciximab use within the last 24 hours.

11. Treatment with a GPIIb/IIIa inhibitor at the time of randomization, which cannot be discontinued.

12. Patients on Arixtra (fondaparinux).

13. Absolute contraindication or allergy to:

- any one of enoxaparin, unfractionated heparin, bivalirudin or aspirin

- both abciximab and eptifibatide

- both eptifibatide and tirofiban

- iodinated contrast which cannot be pre-medicated

14. Contraindications to angiography, including but not limited to severe peripheral vascular disease.

15. Angina from secondary causes.

16. Pregnancy or nursing mothers. Women of child bearing potential must have a negative urine or serum pregnancy test prior to enrollment.

17. Calculated serum creatinine clearance < 30 mL/min (Determined by the Cockcroft Gault formula: ((140-age in yrs) x weight in kg)/(814.464 x Creatinine in mmol/l) or /(72 x [Creatinine in mg/dL]). For women, multiply by 0.85.

18. Previous enrollment in this study.

19. Patients currently enrolled in another investigational drug study that has not completed the follow-up phase.

Tova Rothschild, PhD      973-647-6041    tova.rothschild@themedco.com

New York
      Cardiovascular Research Foundation, New York,  New York,  10022,  United States; Recruiting

Study ID Numbers:  TMC-BIV-02-08
Record last reviewed:  October 2004
Record first received:  October 4, 2004
ClinicalTrials.gov Identifier:  NCT00093158
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2004-11-17