EINSTEIN-Jr Phase 3 Study Supports the Use of Xarelto to Treat VTE in Pediatric Patients
July 8, 2019—The Janssen Pharmaceutical Companies of Johnson & Johnson announced new results from the phase 3 EINSTEIN-Jr study, showing that pediatric patients treated with Xarelto (rivaroxaban) had a similar low risk of recurrent venous thromboembolism (VTE) and similar rates of bleeding when compared to current standard anticoagulation therapy. EINSTEIN-Jr is sponsored by Janssen and Bayer.
The results also show that the efficacy and safety profile of Xarelto in a pediatric population with VTE is comparable to what has been observed in previous studies of adults with VTE. The full findings were presented during a late-breaking session at the 27th Congress of the International Society on Thrombosis and Hemostasis held July 6–10 in Melbourne, Australia.
The company noted that current guidelines recommend that young patients with VTE be treated with standard anticoagulation therapy; however, for these patients, physicians manipulate adult dosage forms of these older anticoagulants, many of which require injections and regular laboratory monitoring.
Christoph Male, MD, commented in Janssen's announcement, "This trial examined for the first time whether a direct oral anticoagulant could alleviate the burden of blood clots in young patients, which would allow them to focus on recovering from their other health challenges. The EINSTEIN-Jr study with rivaroxaban represents a significant advance for pediatric VTE treatment." Dr. Male is with the Department of Pediatrics at Medical University of Vienna in Vienna, Austria.
According to the company, the main efficacy outcome of EINSTEIN-Jr was symptomatic recurrent VTE (fatal or nonfatal), and the principal safety outcome was the composite of major and clinically relevant nonmajor bleeding. The study met all of its prespecified endpoints.
Investigators reported the following observations:
- Recurrent VTE was similar in both treatment groups, with a lower number of events in patients treated with Xarelto. Specifically, 1.2% of the Xarelto group and 3.0% of the standard anticoagulation group experienced a recurrent event (hazard ratio [HR], 0.4; 95% confidence interval [CI], 0.11–1.41). There were no fatal VTE events in either treatment arm.
- Clinically relevant bleeding was also similar, occurring in 3.0% of the Xarelto group and 1.9% of the standard anticoagulation group (HR, 1.58; 95% CI, 0.51–6.27). There were no major bleeding events in the Xarelto group, and two major bleeding events in the standard anticoagulant group.
- The composite of recurrent VTE and major bleeding (net clinical benefit) occurred in 1.2% of the Xarelto group and 4.2% of the standard anticoagulation group (HR, 0.3; 95% CI, 0.08–0.93).
- The efficacy of Xarelto was further demonstrated by reduction in clot burden on imaging tests that were conducted on patients both at baseline and at the end of the treatment period. Complete resolution of the initial VTE mass occurred in 38.5% of the Xarelto group compared to 26.1% of the standard anticoagulation group (overall response, 1.72; 95% CI, 1.12–2.69).
The phase 3 EINSTEIN-Jr randomized, open-label study evaluated the efficacy and safety of Xarelto compared to standard anticoagulation therapy in 500 children from birth to 17 years with previously diagnosed acute VTE who had started heparin therapy. Children were enrolled from 107 sites in 28 countries. Patients were enrolled from November 2014 to September 2018 and were assigned in a 2:1 ratio to receive either an open-label, bodyweight-adjusted dose of Xarelto (n = 335) or standard anticoagulation therapy (n = 165).
Approximately 90% of enrolled patients had conditions in which VTE is a known risk factor. Major surgery/trauma, major infectious diseases, major organ diseases, and active cancer were among the most common conditions.
For the index event, VTE was symptomatic in approximately 80% of participants and asymptomatic in approximately 20%. Of those enrolled, 23.4% had cerebral vein or sinus VTE, 25.4% had catheter-related VTE, and 51.2% had other non–catheter-related VTE as their index event, reported Janssen.