Investigators reported a 3% difference in clinically relevant bleeding in participants treated with rivaroxaban and aspirin.
The Janssen Pharmaceutical Companies of Johnson & Johnson recently announced new data from the Phase 3 UNIVERSE study that showed that treatment with rivaroxaban (XARELTO®) in an oral suspension formulation, was associated with numerically fewer blood clots and clinical events strongly associated with blood clots in pediatric patients aged 2-8 years who had undergone the Fontan procedure, compared to treatment with aspirin.
The findings were published in the Journal of the American Heart Association, and the study was led by Brian W. McCrindle, MD, MPH, The Hospital for Sick Children, Toronto, Canada.
McCrindle and fellow investigators noted that the Fontan procedure has been performed in children with congenital heart disease, and how many who undergo the procedure face significant morbidity and mortality stemming from thrombotic events.
As such, the UNIVERSE study evaluated the efficacy and safety of the novel liquid rivaroxaban formulation versus acetylsalicylic acid (ASA), or aspirin, in children post‐Fontan.
From November 2016 to June 2019, a total of 112 participating children were enrolled in the study.
Participants were enrolled across 35 sites in 10 countries.
Part A of the study was a single-arm part that determined the pharmacokinetics/pharmacodynamics and safety of rivaroxaban in 12 participants.
Part B was comprised of 100 participants who were randomized 2:1 top open-label rivaroxaban versus aspirin.
The primary safety outcome was defined by the International Society on Thrombosis and Haemostasis (ISTH) and included major bleeding events.
The secondary safety outcomes were clinically relevant non-major bleeding and trivial bleeding events, while the primary efficacy outcome was any thrombotic event defined as the appearance of a new thrombotic burden within the cardiovascular system noted on either routine surveillance or clinically indicated imaging, as well as the occurrence of a clinical event known to be strongly associated with thrombus.
Investigators found that the prevalence and pattern of adverse events were comparable between rivaroxaban and aspirin, with clinically relevant bleeding having occurred in 6% and 9% of participants, respectively.
Additionally, trivial bleeding occurred in 33% of participants who were treated with rivaroxaban and 35% of participants who were treated with aspirin.
Fewer participants who were treated with rivaroxaban experienced thrombotic events when compared to the aspirin group, though investigators noted that the study was not powered for efficacy outcomes.
In a press release by Janssen Pharmaceutical, Brian W. McCrindle, MD, MPH, Pediatric Cardiologist at the Hospital for Sick Children in Toronto, noted that health care providers had often been limited in their options for reducing potentially fatal thrombotic events in post-Fontan child patients.
However, the data obtained in phase 3 of the UNIVERSE study suggested a possible alternative to aspirin in rivaroxaban.
"We now not only have data suggesting that rivaroxaban has a similar positive effect and safety as aspirin, but we also have identified an age-appropriate formulation with precise weight-based dosing to help manage our young patients during a critical time," McCrindle said.
The study, “Thromboprophylaxis for Children Post‐Fontan Procedure: Insights From the UNIVERSE Study,” was published in the Journal of the American Heart Association.