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Phase 3 Completed N=803 Randomized Treatment

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

Source: ClinicalTrials.gov NCT01651780 ↗
Enrolled (actual)
803
Serious AEs
29.0%
Results posted
Feb 2017
Primary outcomePrimary: Major Bleeding (BARC ≥3b) at 48 Hours or Before Hospital Discharge — 6.9; 9 percentage of participants — p=0.2692
◆ Published Evidence
Highly cited
122citations · ~11 / year
Bivalirudin Versus Heparin Anticoagulation in Transcatheter Aortic Valve Replacement: The Randomized BRAVO-3 Trial.
Journal of the American College of Cardiology · 2015 · Likely link

Summary

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). The primary hypothesis of BRAVO 3 was that bivalirudin would reduce major bleeding compared with heparin in TAVR procedures. Results for all participants enrolled into the randomized trial (BRAVO 3) are presented.

Linked Publications (2)

  • Bivalirudin Versus Heparin Anticoagulation in Transcatheter Aortic Valve Replacement: The Randomized BRAVO-3 Trial.
    Journal of the American College of Cardiology · 2015 · 122 citations · Likely link
  • Cerebral Embolism During Transcatheter Aortic Valve Replacement: The BRAVO-3 MRI Study.
    Journal of the American College of Cardiology · 2016 · 53 citations · Likely link

Outcome Measures

OutcomeResultp-value
PRIMARY
Major Bleeding (BARC ≥3b) at 48 Hours or Before Hospital Discharge
6.9; 9 0.2692
PRIMARY
Net Adverse Clinical Events (NACE) at up to 30 Days
14.4; 16.1 0.4967
SECONDARY
NACE at 48 Hours or Before Hospital Discharge
8.9; 12.6
SECONDARY
Major Adverse Cardiac Events (MACE) Including Death, Non-fatal MI, and Stroke
3.5; 4.8; 1.5; 1.8; 0; 1.3
SECONDARY
Major Bleeding According to Additional Scales (VARC, TIMI, GUSTO, ACUITY/HORIZONS)
21.8; 19.6; 4; 6.5; 13.9; 11.6
SECONDARY
Transient Ischemic Attack
0; 0; 0; 0
SECONDARY
Acute Kidney Injury
10.9; 6.5; 18.8; 13.8
SECONDARY
Major Vascular Complications
8.7; 9; 9.2; 9.5
SECONDARY
Acquired Thrombocytopenia
16.6; 17.3; 24; 23.1
SECONDARY
New Onset Atrial Fibrillation/Flutter
3.2; 2.5; 5.4; 4
SECONDARY
Timing Effect on Bleeding Event Rate up to 48 Hours or Hospital Discharge
6.4; 6.4; 11.6; 8.5
SECONDARY
Bleeding BARC 3a, BARC Types 1 or 2, and TIMI Minor
15.6; 13.3; 20.8; 21.1; 16.6; 14.3

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
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01651780) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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