Patients undergoing transcatheter aortic valve replacement (TAVR) procedures performed via the transfemoral approach. MedDRA version: 17.0 Level: PT Classification code 10002916 Term: Aortic valve replacement System Organ Class: 10042613 - Surgical and medical procedures
Conditions
Interventions
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Pharmaceutical Form: Powder for concentrate for solution for injection/infusion
Sponsors
The Medicines Company
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients may be included in the study if they meet all of the following criteria: 1. = 18 years of age 2. High risk (Euroscore =18, or considered inoperable) for surgical aortic valve replacement 3. Undergoing TAVR via transfemoral arterial access 4. Provide written informed consent before initiation of any study related procedures 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 261 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 609
Exclusion criteria
Exclusion criteria: Patients will be excluded from the study if any of the following exclusion criteria apply prior to enrollment: 1. Any known contraindication to the use of bivalirudin (except presence of severe renal impairment [GFR<30 ml/min] since these patients will be included in the trial - please see protocol section 8.1.1) or UFH 2. Refusal to receive blood transfusion 3. Mechanical valve (any location) or mitral bioprosthetic valve 4. Extensive calcification of the common femoral artery, or minimal luminal diameter < 6.5 mm 5. Use of elective surgical cut-down for transfemoral access 6. Concurrent performance of percutaneous coronary intervention with TAVR 7. International normalized ratio (INR) = 2 on the day of TAVR procedure, or known history of bleeding diathesis 8. History of hemorrhagic stroke, intracranial hemorrhage, intracerebral mass or aneurysm, or arteriovenous malformation 9. Severe left ventricular dysfunction (left ventricular ejection fraction<15%) 10. Severe aortic regurgitation or mitral regurgitation (4+) 11. Hemodynamic instability (e.g. requiring inotropic or IABP support) within 2 hours of the procedure 12. Dialysis dependent 13. Administration of thrombolytics, glycoprotein IIb/IIIa inhibitors, or warfarin in the 3 days prior to the procedure 14. Acute myocardial infarction, major surgery or any therapeutic cardiac procedure (other than balloon aortic valvuloplasty) within 30 days 15. Percutaneous coronary intervention within 30 days 16. Upper gastrointestinal or genitourinary bleed within 30 days 17. Stroke or transient ischemic attack within 30 days 18. Any surgery or biopsy within 2 weeks 19. Administration of: a. UFH within 30 minutes of the procedure, b. Enoxaparin within 8 hours of the procedure c. Fondaparinux or other LMWHs within 24 hours of the procedure d. Dabigatran, rivaroxaban or other oral anti-Xa or antithrombin agent within 48 hours of the procedure e. Thrombolytics, GPI, or warfarin within 72 hours of the procedure 20. Absolute contraindications or allergy that cannot be pre-medicated to iodinated contrast 21. Contraindications or allergy to aspirin or clopidogrel 22. 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. 23. Previous enrolment in this study 24. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of this study is to assess the safety and efficacy of using bivalirudin instead of unfractionated heparin (UFH) in transcatheter aortic valve replacements (TAVR).;Secondary Objective: There is no secondary objective.; Primary end point(s): The primary end point will be major bleeding defined as Bleeding Academic Research Consortium (BARC) type =3b at 48 hours or hospital discharge whichever occurs first. BARC type 3b bleeding includes bleeds that are evident clinically, or by laboratory or imaging results, which result in surgical intervention or administration of intravenous vasoactive drugs; overt bleeds with a hemoglobin drop of at least 5g/dL; and bleeding that causes cardiac tamponade. BARC 3c bleeding includes intracranial or intraocular bleeds that compromise vision. BARC type 4, CABG related bleeding, includes perioperative intracranial bleeding within 48 hours; bleeds that result in reoperation following closure of sternotomy for the purpose of controlling bleeding; bleeds that result in treatment with transfusion of =5 units of whole blood or packed red blood cells within a 48 hour period; and chest tube output = 2L within a 24 hour period. BARC type 5, fatal bleeding, describes bleeds that directly result in death with no other cause. The co-primary endpoint will be net adverse cardiac events (NACE) at up to 30 days that is the composite of major adverse cardiovascular events (MACE) + major bleeding (BARC type =3). The composite of major adverse cardiovascular events (MACE) is defined as all-cause mortality, myocardial infarction, and stroke. All events will be adjudicated using source documents by an independent clinical events committee blinded to the antithrombotic agents. Each component of the co-primary endpoint will be tested in a hierarchical manner with a superiority test for bleeding followed by a non-inferiority and then superiority test for NACE. ; | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints of this trial are:(1) Major bleeding according to additional scales (VARC, TIMI, GUSTOACUITY/HORIZONS); (2) Bleeding BARC =3; moderate bleeding BARC = 3a; minor bleeding (BARC type 1 and 2 and TIMI minor); (3) major adverse cardiac events (MACE) including death, non-fatal MI, and stroke; (4) the rates of the individual components of MACE; (5) transient ischemic attack; (6) acute kidney injury; (7) VARC major vascular complications; (8) acquired thrombocytopenia; (9) rate of new post-procedural atrial fibrillation/flutter; and (10) economic analysis of using bivalirudin in TAVR. All end points will be assessed at 48 hours post-procedure (or prior to hospital discharge, if that occurs earlier) and at up to 30-days. With respect to the economic analysis, the analysis time point will be fixed to the hospital discharge (but also include any subsequent hospitalizations).; Timepoint(s) of evaluation of this end point: 48 hours or prior to hospital discharge (whichever occurs first) and at up to 30 days | — |
Countries
Canada, Germany, Italy, Netherlands, Switzerland, United Kingdom
Contacts
Public ContactGlobal Health Science Center
The Medicines Company
Outcome results
None listed