Intervention: Bivalirudin
Trial phase: Phase 3
ATC code: B01AE06
SMILES: CC[C@H](C)[C@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)CNC(=O)CNC(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](N)Cc1ccccc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(C)C)C(=O)O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 393
Group description: Bivalirudin administered as a bolus and intravenous (IV) infusion during TAVR. It was recommended that the bolus (0.75 milligrams per kilogram [mg/kg]) be directly administered through the valve delivery sheath immediately following its successful delivery via percutaneous femoral access. Systemic IV administration of the bolus dose was also acceptable. The bivalirudin IV infusion was initiated immediately after the bolus administration. All wires, catheters, and sheaths were to be flushed with heparinized saline.
Eligibility criteria:
Inclusion Criteria:

Males and females, ≥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 [glomerular filtration rate (GFR) <30 milliliters (mL)/minute] since these participants 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 millimeters (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 (for example, requiring inotropic or intra-aortic balloon pump support) within 2 hours of the procedure
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 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 low-molecular-weight heparins (LMWHs) within 24 hours of the procedure
Dabigatran, rivaroxaban, or other oral anti-Xa or antithrombin agent within 48 hours of the procedure
Thrombolytics, glycoprotein IIb/IIIa inhibitor, 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 enrollment 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