Background Patients with single-ventricle physiology who undergo the
Fontan procedure are at risk for thrombotic events associated with significant morbidity and mortality. The UNIVERSE Study evaluated the efficacy and safety of a novel liquid
rivaroxaban formulation, using a
body weight-adjusted dosing regimen, versus
acetylsalicylic acid (ASA) in children post-Fontan. Methods and Results The UNIVERSE Study was a randomized, multicenter, 2-part, open-label study of
rivaroxaban, in children who had undergone a
Fontan procedure, to evaluate its dosing regimen, safety, and efficacy. Part A was the single-arm part of the study that determined the pharmacokinetics/pharmacodynamics and safety of
rivaroxaban in 12 participants before proceeding to part B, whereby 100 participants were randomized 2:1 to open-label
rivaroxaban versus ASA. The study period was 12 months. A total of 112 participants were enrolled across 35 sites in 10 countries. In part B, for safety outcomes, major
bleeding occurred in one participant on
rivaroxaban (
epistaxis that required transfusion). Clinically relevant nonmajor
bleeding occurred in 6% of participants on
rivaroxaban versus 9% on ASA. Trivial
bleeding occurred in 33% of participants on
rivaroxaban versus 35% on ASA. For efficacy outcomes, 1 participant on
rivaroxaban in part B had a
pulmonary embolism (2% overall event rate); and for ASA, 1 participant had
ischemic stroke and 2 had
venous thrombosis (9% overall event rate). Conclusions In this study, participants who received
rivaroxaban for thromboprophylaxis had a similar safety profile and fewer thrombotic events, albeit not statistically significant, compared with those in the ASA group. Registration URL: https://www.clinicaltrials.gov. Identifier: NCT02846532.