International, Multi-center, Open-label, Randomized Controlled Trial in Patients Undergoing TAVR to Determine the Treatment Effect (Both Safety and Efficacy) of Using Bivalirudin Instead of UFH. (BRAVO 2/3)

Inclusion Criteria:

• ≥ 18 years of age
• High risk (Euroscore ≥18, or considered inoperable) for surgical aortic valve replacement
• Undergoing TAVR via transfemoral arterial access
• Provide written informed consent before initiation of any study related procedures

Exclusion Criteria:

• Any known contra‐indication to the use of bivalirudin (except presence of severe renal impairment [GFR<30 ml/min] since these patients will be included in the trial or UFH
• Refusal to receive blood transfusion
• Mechanical valve (any location) or mitral bioprosthetic valve
• Extensive calcification of the common femoral artery, or minimal luminal diameter< 6.5 mm
• Use of elective surgical cut-down for transfemoral access
• Concurrent performance of percutaneous coronary intervention with TAVR
• International normalized ratio (INR) ≥ 2 on the day of TAVR procedure, or known history of bleeding diathesis
• History of hemorrhagic stroke, intracranial hemorrhage, intracerebral mass or aneurysm, or arteriovenous malformation
• Severe left ventricular dysfunction (left ventricular ejection fraction<15%)
• Severe aortic regurgitation or mitral regurgitation (4+)
• Hemodynamic instability (e.g. requiring inotropic or IABP support) within 2 hours of the procedure
• Serum Creatinine >4.0 mg/dL or dialysis dependent
• Administration of thrombolytics, glycoprotein IIb/IIIa inhibitors, or warfarin in the 3 days prior to the procedure
• Acute myocardial infarction, major surgery or any therapeutic cardiac procedure (other than balloon aortic valvuloplasty) within 30 days
• Percutaneous coronary intervention with drug-eluting stent(s) within 30 days
• Upper gastrointestinal or genitourinary bleed within 30 days
• Stroke or transient ischemic attack within 30 days
• Any surgery or biopsy within 2 weeks

• Administration of:

  • UFH within 30 minutes of the procedure
  • Enoxaparin within 8 hours of the procedure
  • Fondaparinux or other LMWHs within 24 hours of the procedure
  • Dabigatran, rivaroxaban or other oral anti-Xa or antithrombin agent within 48 hours of the procedure
  • Thrombolytics, GPI, or warfarin within 72 hours of the procedure
• Absolute contraindications or allergy that cannot be pre-medicated to iodinated contrast
• Contraindications or allergy to aspirin or clopidogrel
• Known or suspected pregnant women, or nursing mothers. Women of child‐bearing potential will be asked if they are pregnant and will be tested for pregnancy
• Previous enrolment in this study
• Treatment with other investigational drugs or devices within the 30 days preceding enrollment or planned use of other investigational drugs or devices before the primary endpoint of this study has been reached Patients excluded for any of the above reasons may be re-screened for participation at any time if the exclusion characteristic has changed.