No major bleeding observed with oral agent in EINSTEIN-Jr trial
Rivaroxaban (Xarelto) worked as a treatment for acute venous thromboembolism (VTE) in pediatric patients, according to a phase III trial.
Both tablet and oral suspension formulations of the non-vitamin K antagonist oral anticoagulant (NOAC) were found to match standard anticoagulation therapy in rates of symptomatic recurrent VTE (1.2% vs 3.0%, HR 0.40, 95% CI 0.11-1.41) and clinically relevant bleeding (3.0% vs 1.9%, HR 1.58, 95% CI 0.51-6.27) over 12 months.
Thus, the EINSTEIN-Jr trial met its safety and efficacy endpoints, Christoph Male, MD, of the Medical University of Vienna, reported at the International Society on Thrombosis and Haemostasis (ISTH) meeting in Melbourne, Australia.
The trial also showed that rivaroxaban pediatric exposure was in the adult target exposure range for both formulations, that the clinical course of VTE was comparable between children and adults treated with the drug, and that relative efficacy and safety were comparable to those in adults, Male told attendees.
Another NOAC, dabigatran (Pradaxa), was also shown to have comparable efficacy and safety as standard of care in children, according to two other studies at ISTH.
No NOAC is currently approved for use in pediatric patients with VTE. For these children, the standard of care is low molecular weight heparin, fondaparinux, and/or an oral vitamin K antagonist. FDA approved the first anticoagulant specifically for pediatric use in April, giving subcutaneous dalteparin (Fragmin) an indication for patients as young as 1 month to reduce risk of symptomatic venous thromboembolism recurrence.
"Treating venous thrombosis in children has typically required using injectable anticoagulants and/or frequent blood testing, both of which can cause pain and distress. So finding a comparable oral anticoagulant could be practice-changing," commented Margaret Fang, MD, of the University of California San Francisco Medical Center.
EINSTEIN-Jr "paves the way for larger trials that can establish the safety and efficacy [of] using direct oral anticoagulants in children," Fang told MedPage Today.
EINSTEIN-Jr included 500 patients from birth up to age 18 years who were enrolled at 28 countries.
Just over half of the cohort had non-catheter related VTE, a quarter had catheter-related clots, and another quarter had cerebral vein or sinus thrombosis.
These kids had already started heparin therapy and required anticoagulation for at least 90 days. They were randomized 2:1 to rivaroxaban and control groups. Rivaroxaban was administered at age- and weight-adjusted doses that were equivalent to a 20-mg exposure in adults.
Investigators observed no major bleeds with the experimental arm but two with standard of care, although the difference was not significant.
The UNIVERSE trial is underway to see how rivaroxaban works after the Fontan procedure among children ages 2 to 8 years.
EINSTEIN-Jr was sponsored by Janssen and Bayer.
Male reported relationships with Bayer, Bristol-Myers Squibb, Pfizer, and Boehringer Ingelheim.
Read the original article on Medpage Today: Children Benefit From NOACs for Acute VTE