Open-label, Randomized Trial in Patients Undergoing TAVR to Determine Safety & Efficacy of Bivalirudin vs UFH

Aortic Valve Insufficiency Clinical Trial

— BRAVO-2/3  

Official title:

Effect of Bivalirudin on Aortic Valve Intervention Outcomes 2/3 (BRAVO 2/3)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01651780
• Other study ID #: Protocol No. TMC-BIV-11-02
• Secondary ID: 2012-000632-26
• Status: Completed
• Phase: Phase 3
• First received: July 24, 2012
• Last updated: October 27, 2015
• Start date: October 2012
• Est. completion date: August 2015

Study information

• Verified date: October 2015
• Source: The Medicines Company
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santéFrance: Committee for the Protection of PersonnesGermany: Federal Institute for Drugs and Medical DevicesGermany: Ethics CommissionItaly: Ethics CommitteeNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Netherlands: Medical Ethics Review Committee (METC)United Kingdom: Medicines and Healthcare Products Regulatory AgencySwitzerland: EthikkommissionCanada: Ethics Review CommitteeItaly: The Italian Medicines AgencyUnited Kingdom: Research Ethics CommitteeUnited Kingdom: National Institute for Health ResearchSwitzerland: SwissmedicCanada: Health CanadaGermany: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

This is an international, multicenter, open-label, randomized controlled trial. All patients undergoing transfemoral TAVR at the participating centers will be eligible. All sites will initiate enrolment with 2 feasibility roll-in bivalirudin treated patients and thereafter patients will be randomly assigned to either standard dosing of bivalirudin or UFH as control. The 2 roll-in cases per site will constitute the feasibility cohort that will be followed and analyzed separately. Patients will undergo TAVR according to current standard of care practices at the treating centers. Use of antiplatelet agents pre, during, and post procedure, and possibly oral anticoagulants post procedure, will be according to the sites' standard practice. ALL available data will be collected in the eCRF prospectively

Description:

This study will be an international, multi-center, open-label, randomized controlled trial in patients undergoing TAVR. Following the conclusion of the roll-in phase of 2 patients per site, who will comprise the feasibility cohort of approximately 70 patients, 550 patients will be randomized to bivalirudin or UFH at approximately 35 centers. Informed consent will be obtained from patients meeting the inclusion criteria before the initiation of any study-specific procedures.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 868
• Est. completion date: August 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

• 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 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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Aortic Valve Insufficiency
• Aortic Valve Replacement
• Aortic Valve Stenosis
• Severe Aortic Stenosis
• Transcatheter Aortic Valve Replacement

Intervention

Procedure:
• Trans-Aortic Valve Replacement
transcatheter aortic valve replacement (TAVR) procedures performed via the transfemoral approach

Locations

Country	Name	City	State
Canada	Montreal Heart Institute	Montreal	Quebec
Canada	St. Paul´s Hospital Providence Health Care	Vancouver
France	CHU Jean Minjoz, Service de Cardiologie	Besançon
France	Centre Hospitalier de Lyon	Bron
France	Department of Cardiology, CHRU Lille	Lille
France	Institut Hospitalier Jacques Cartier	Massy
France	Service de Cardiologie, Centre Hospitalo-Universitaire, Hôpital Charles-Nicolle	Rouen
France	CHU de Toulouse	Toulouse	Cedex 9
France	Clinique Pasteur, Unité de Cardiologie Interventionnelle	Toulouse	Cedex 3
Germany	Universitätsklinikum Bonn	Bonn
Germany	Klinikum links der Weser Bremen	Bremen
Germany	Elisabeth-Krankenhaus Essen	Essen
Germany	Freiburg University	Freiburg
Germany	Asklepios St. Georg Hamburg	Hamburg
Germany	Universitätsklinikum Hamburg-Eppendorf	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover
Germany	University Heart Centre, Clinic of Inner Medicine 1 Cardiology	Jena	Lobeda Ost
Germany	Universität Leipzig - Herzzentrum GmbH	Leipzig
Germany	Universitätsmedizin der Johannes Gutenberg-Universitat Mainz	Mainz
Germany	Deutsches Herzzentrum München	München
Germany	LMU Munich, Klinikum der Universität München	Munich
Germany	Helios Heart Center Siegburg	Siegburg
Italy	Ferraroto Hospital, University of Catania	Catania
Italy	Ospedale San Raffaele U.O. Cardiologia Interventistica	Milano
Italy	Azienda Ospedaliero-Universitaria Pisana	Pisa
Italy	Azienda Ospedaliera San Camillo-Forlanini	Roma
Italy	Policlinico Umberto I, Università La Sapienza	Roma
Netherlands	St. Antonius Ziekenhuis	Nieuwegein
Netherlands	University Medical Center Utrecht	Utrecht
Switzerland	Cardiology University Hospital Basel	Basel
Switzerland	Universitätsklinik Bern	Bern
United Kingdom	The Royal Sussex County Hospital	Brighton	East Sussex
United Kingdom	Hammersmith Hospital	London

Sponsors (1)

Lead Sponsor	Collaborator
The Medicines Company

Countries where clinical trial is conducted

Canada,  France,  Germany,  Italy,  Netherlands,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Major Bleeding	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.	48 hours post-procedure or discharge	Yes
Secondary	Bleeding	The secondary endpoints of this trial are: (1) Major bleeding according to additional scales (VARC, TIMI, GUSTO, ACUITY/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.	48 hours post-procedure or discharge	Yes