AB0451 Rivaroxaban versus warfarin as secondary thromboprophylaxis in patients with antiphospholipid syndrome protocol: a randomized, multicentre, open-label, clinical trial

Abstract

Background: Long-term anticoagulation is widely used for secondary thromboprophylaxis in the antiphospholipid syndrome (APS) due to the high risk of recurrent events. Currently anticoagulation with vitamin K antagonists (VKAs) is the standard of care but have unpredictable pharmacodynamic properties that requiere monitoring for dose adjustment. Rivaroxaban, an orally active direct factor Xa inhibitor, has been shown to be effective and safe compared with warfarin for the treatment of venous thromboembolism and non valvular atrial fibrillation in major RCTs. No studies had been published in APS. Objectives: To investigate the efficacy and safety of rivaroxaban in preventing recurrent thrombosis in patients with APS compared with warfarin. Methods: This is a phase 3 randomized, multicenter, non-inferiority open-label RCT . 190 eligible APS patients with arterial or venous thrombotic history receiving warfarin will be stratified according the presence of SLE and venous/arterial thrombotic history and randomized (1:1) either to continue warfarin (standard of care, normalized ratio (INR) 2-3 or 2.5 to 3.5 in those with recurrent thrombotic episodes) or to switch to rivaroxaban (20 mg/day). The primary efficacy outcome is the development of any thrombotic event during the study period. Secondary efficacy outcomes include time to thrombosis, type of thrombosis (arterial or venous), overall causes of death, evaluation of a prognostic biomarker panel of recurrent thrombosis. The primary safety outcome will be major bleeding. Secondary safety outcomes include any adverse event and minor bleeding. The study has 3 years follow-up. First patient was included in March 2013 (EUDRA-CT:2010-019764-36). Conclusions: If the study demonstrates a non-inferior anticoagulant effect compared with warfarin, this would provide sufficient supporting evidence to make rivaroxaban a standard of care for the treatment of patients with APS with previous thrombotic history.