title: Trial design: Rivaroxaban for the prevention of major cardiovascular events after transcatheter aortic valve replacement: Rationale and design of the GALILEO study.
abstract: BACKGROUND
  Optimal antithrombotic treatment after transcatheter aortic valve replacement (TAVR) is unknown and determined empirically. The direct factor Xa inhibitor rivaroxaban may potentially reduce TAVR-related thrombotic complications and premature valve failure.
  
  
  METHODS
  GALILEO is an international, randomized, open-label, event-driven, phase III trial in more than 1,520 patients without an indication for oral anticoagulation who underwent a successful TAVR (ClinicalTrials.govNCT02556203). Patients are randomized (1:1 ratio), 1 to 7days after a successful TAVR, to either a rivaroxaban-based strategy or an antiplatelet-based strategy. In the experimental arm, subjects receive rivaroxaban (10mg once daily [OD]) plus acetylsalicylic acid (ASA, 75-100mg OD) for 90days followed by rivaroxaban alone. In the control arm, subjects receive clopidogrel (75mg OD) plus ASA (as above) for 90days followed by ASA alone. In case new-onset atrial fibrillation occurs after randomization, full oral anticoagulation will be implemented with maintenance of the original treatment assignment. The primary efficacy end point is the composite of all-cause death, stroke, myocardial infarction, symptomatic valve thrombosis, pulmonary embolism, deep venous thrombosis, and systemic embolism. The primary safety end point is the composite of life-threatening, disabling, and major bleeding, according to the Valve Academic Research Consortium definitions.
  
  
  CONCLUSIONS
  GALILEO will test the hypothesis that a rivaroxaban-based antithrombotic strategy reduces the risk of thromboembolic complications post-TAVR with an acceptable risk of bleeding compared with the currently recommended antiplatelet therapy-based strategy in subjects without need of chronic oral anticoagulation.
authors.affiliation: Bern University Hospital, Bern, Switzerland; European Cardiovascular Research Institute (ECRI), Rotterdam, the Netherlands. Electronic address: stephan.windecker@insel.ch.
authors.forename: Stephan
authors.initials: S
authors.lastname: Windecker
authors.affiliation: European Cardiovascular Research Institute (ECRI), Rotterdam, the Netherlands; Academic Medical Center-University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Tijssen
authors.affiliation: The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York City.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Giustino
authors.affiliation: Cardialysis, Clinical Research Organization, Rotterdam, the Netherlands.
authors.forename: Ana H C
authors.initials: AH
authors.lastname: Guimarães
authors.affiliation: The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York City.
authors.forename: Roxana
authors.initials: R
authors.lastname: Mehran
authors.affiliation: Bern University Hospital, Bern, Switzerland; European Cardiovascular Research Institute (ECRI), Rotterdam, the Netherlands.
authors.forename: Marco
authors.initials: M
authors.lastname: Valgimigli
authors.affiliation: Hartcentrum Hasselt, Hasselt, Belgium; European Cardiovascular Research Institute (ECRI), Rotterdam, the Netherlands.
authors.forename: Pascal
authors.initials: P
authors.lastname: Vranckx
authors.affiliation: Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Welsh
authors.affiliation: The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York City.
authors.forename: Usman
authors.initials: U
authors.lastname: Baber
authors.affiliation: European Cardiovascular Research Institute (ECRI), Rotterdam, the Netherlands; Cardialysis, Clinical Research Organization, Rotterdam, the Netherlands.
authors.forename: Gerrit-Anne
authors.initials: GA
authors.lastname: van Es
authors.affiliation: Janssen Pharmaceuticals Inc., Raritan, NJ.
authors.forename: Peter
authors.initials: P
authors.lastname: Wildgoose
authors.affiliation: Janssen Pharmaceuticals Inc., Raritan, NJ.
authors.forename: Albert A
authors.initials: AA
authors.lastname: Volkl
authors.affiliation: Bayer, São Paulo, Brazil.
authors.forename: Ana
authors.initials: A
authors.lastname: Zazula
authors.affiliation: Bayer Pharma AG, Berlin, Germany.
authors.forename: Karen
authors.initials: K
authors.lastname: Thomitzek
authors.affiliation: Bayer Pharma AG, Berlin, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Hemmrich
authors.affiliation: The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York City.
authors.forename: George D
authors.initials: GD
authors.lastname: Dangas
mesh_terms: D001024:Aortic Valve Stenosis / Q000601:surgery*; D001241:Aspirin / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000517:prevention & control*; D002423:Cause of Death; D000077144:Clopidogrel; D004359:Drug Therapy, Combination; D004617:Embolism / Q000453:epidemiology / Q000517:prevention & control; D065427:Factor Xa Inhibitors / Q000627:therapeutic use*; D006349:Heart Valve Diseases / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D009026:Mortality; D009203:Myocardial Infarction / Q000453:epidemiology / Q000517:prevention & control; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011182:Postoperative Care / Q000379:methods; D011655:Pulmonary Embolism / Q000453:epidemiology / Q000517:prevention & control; D000069552:Rivaroxaban / Q000627:therapeutic use*; D020521:Stroke / Q000453:epidemiology / Q000517:prevention & control; D013927:Thrombosis / Q000453:epidemiology / Q000517:prevention & control; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D065467:Transcatheter Aortic Valve Replacement; D020246:Venous Thrombosis / Q000453:epidemiology / Q000517:prevention & control
chemical_list: D065427:Factor Xa Inhibitors; D010975:Platelet Aggregation Inhibitors; D000069552:Rivaroxaban; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin