Trial design: Rivaroxaban for the prevention of major cardiovascular events after transcatheter aortic valve replacement: Rationale and design of the GALILEO study.

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. DESIGN: 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.