The Jansen Pharmaceutical Companies of Johnson & Johnson recently announced new data from the Phase III UNIVERSE study which demonstrated treatment with rivaroxaban in an oral suspension formulation, compared to treatment with aspirin, was associated with blood clots in pediatric patients who have undergone the Fontan procedure.
The Fontan procedure is performed in children with congenital heart disease who have a single functioning ventricle to redirect blood flow to the lungs to be reoxygenated. Children who undergo the Fontan procedure often face significant morbidity and mortality stemming from thrombotic events, especially during the critical 3- to 12-month period following the procedure. While it is common for physicians to prescribe aspirin, there are limited data regarding aspirin resistance or the optimal dose for thromboprophylaxis in children.
“For years, health care providers have had limited options to help reduce potentially fatal thrombotic events that often occur in young children following the Fontan procedure,” said Brian W. McCrindle, M.D., MPH, Pediatric Cardiologist at the Hospital for Sick Children in Toronto via a press release. “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.”
The UNIVERSE study was conducted in two parts: Part A evaluated pharmacokinetic (PK) and pharmacodynamic (PD) properties of XARELTO®, while Part B assessed the safety and efficacy of XARELTO® compared to aspirin when used for thromboprophylaxis for 12 months.
The primary safety endpoint was defined as major bleeding events defined by the International Society on Thrombosis and Hemostasis (ISTH). The secondary safety outcomes were stipulated as clinically relevant non-major bleeding and trivial (minimal) bleeding events. The primary efficacy outcome was any thrombotic event (venous or arterial) defined as the appearance of a new thrombotic burden within the cardiovascular system noted on either routine surveillance or clinically indicated imaging, or the occurrence of a clinical event known to be strongly associated with thrombus.
The results showed a comparable and low prevalence of bleeding events was observed with XARELTO® compared to aspirin. The researchers noted that there was was one major non-fatal bleeding event (nosebleed) with XARELTO®, and compared to aspirin, a slightly lower prevalence of non-major clinically relevant bleeding (6 vs. 9 percent of participants) and trivial bleeding (33 vs. 35 percent of participants). The prevalence and pattern of adverse events were comparable between the two groups. Moreover, the UNIVERSE study demonstrated that there fewer thrombotic events with XARELTO®, though the study was not powered for efficacy outcomes.
“The promise of the EXPLORER research program for XARELTO® was to uncover new insights into how the medical community can help improve the care of patients who are faced with thrombotic risk, from young to old,” said James List, M.D., Ph.D., Global Therapeutic Area Head, Cardiovascular, Metabolism, & Retina, Janssen Research & Development, LLC. “The UNIVERSE study is another example of our fulfillment of that promise, and we’re optimistic these findings will generate greater understanding and help to inform guidance for physicians managing thrombotic complications in these vulnerable and high-risk pediatric patients.”