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)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by The Medicines Company
Sponsor:
Information provided by (Responsible Party):
The Medicines Company
ClinicalTrials.gov Identifier:
NCT01651780
First received: July 24, 2012
Last updated: March 6, 2014
Last verified: March 2014
  Purpose

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


Condition Intervention Phase
Severe Aortic Stenosis
Aortic Valve Insufficiency
Transcatheter Aortic Valve Replacement
Aortic Valve Replacement
Procedure: Trans-Aortic Valve Replacement
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effect of Bivalirudin on Aortic Valve Intervention Outcomes 2/3 (BRAVO 2/3)

Resource links provided by NLM:


Further study details as provided by The Medicines Company:

Primary Outcome Measures:
  • Major Bleeding [ Time Frame: 48h post or discharge ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Bleeding [ Time Frame: 48 hours post-procedure ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 620
Study Start Date: October 2012
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bivalirudin during Trans-Aortic Valve Replacement
Bivalirudin will be administered as a bolus and infusion. It is recommended that the bolus (0.75 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 is also acceptable. The bivalirudin intravenous infusion is initiated immediately after the bolus administration
Procedure: Trans-Aortic Valve Replacement
transcatheter aortic valve replacement (TAVR) procedures performed via the transfemoral approach
Other Name: TAVR
Active Comparator: Unfractionated heparin during Trans-Aortic Valve Replacement
The dose of UFH should adhere to the standard institutional practice. An ACT target ≥ 250 seconds is recommended
Procedure: Trans-Aortic Valve Replacement
transcatheter aortic valve replacement (TAVR) procedures performed via the transfemoral approach
Other Name: TAVR

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01651780

Contacts
Contact: Eberhardt Grube, MD grubeE@aol.com
Contact: Thierry Lefevre, MD t.lefevre@angio-icps.com

Locations
Canada
St. Paul´s Hospital Providence Health Care Active, not recruiting
Vancouver, Canada, V6Z1Y6
France
CHU Toulouse Active, not recruiting
Toulouse, Cedex9, France, 31059
Germany
Deutsches Herzzentrum München Recruiting
München, Germany, 80636
Contact: Christian Hengstenberg, MD       hengstenberg@dhm.mhn.de   
Principal Investigator: Christian Hengstenberg, MD         
Italy
Ospedale San Raffaele U.O. Cardiologia Interventistica Recruiting
Milano, Italy, 20132
Contact: Antonio Colombo, MD       colombo.antonio@hsr.it   
Principal Investigator: Antonio Colombo, MD         
Netherlands
St. Antonius Ziekenhuis Recruiting
Nieuwegein, Netherlands, 3435
Contact: Jur ten Berg, MD       j.ten.berg@antoniusziekenhuis.nl   
Principal Investigator: Jur ten Berg, MD         
Switzerland
Universitätsklinik Bern Recruiting
Bern, Switzerland, 3010
Contact: Stephan Windecker, MD       stephan.windecker@insel.ch   
Principal Investigator: Stephan Windecker, MD         
United Kingdom
The Royal Sussex County Hospital Recruiting
Brighton, East Sussex, United Kingdom, BN2 5BE
Contact: David Hildick-Smith, MD         
Principal Investigator: David Hildick-Smith, MD         
Sponsors and Collaborators
The Medicines Company
Investigators
Principal Investigator: Thierry Lefevre, MD Hôpital Privé Jacques Cartier
Study Director: Prodromos Anthopoulos, MD The Medicines Company
Principal Investigator: Eberhardt Grube, MD Universitätsklinikum Bonn
  More Information

No publications provided

Responsible Party: The Medicines Company
ClinicalTrials.gov Identifier: NCT01651780     History of Changes
Other Study ID Numbers: Protocol No. TMC-BIV-11-02, 2012‐000632‐26
Study First Received: July 24, 2012
Last Updated: March 6, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
France: Committee for the Protection of Personnes
Germany: Federal Institute for Drugs and Medical Devices
Germany: Ethics Commission
Italy: Ethics Committee
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Netherlands: Independent Ethics Committee
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Switzerland: Ethikkommission
Canada: Ethics Review Committee

Keywords provided by The Medicines Company:
Transcatheter aortic valve replacement
aortic valve replacement
aortic valve insufficiency
severe aortic stenosis

Additional relevant MeSH terms:
Aortic Valve Insufficiency
Aortic Valve Stenosis
Cardiovascular Diseases
Heart Diseases
Heart Valve Diseases
Ventricular Outflow Obstruction
Bivalirudin
Anticoagulants
Antithrombins
Enzyme Inhibitors
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Serine Proteinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014