A New Drug Application (NDA) has been submitted to the Food and Drug Administration (FDA) for rivaroxaban (Xarelto®) for 2 new pediatric indications: treatment of venous thromboembolism (VTE) and reduction in the risk of recurrent VTE in patients aged from birth to less than 18 years after at least 5 days of initial parenteral anticoagulant treatment; and thromboprophylaxis in patients 2 years of age and older with congenital heart disease who have undergone the Fontan procedure.

The NDA submission is supported by data from two phase 3 trials in pediatric patients, UNIVERSE (ClinicalTrials.gov Identifier: NCT02846532) and EINSTEIN-Jr (ClinicalTrials.gov Identifier: NCT02234843), along with adequate and well-controlled studies in adults. The UNIVERSE study compared the efficacy and safety of a novel, oral suspension of rivaroxaban with aspirin for thromboprophylaxis in 112 children aged 2 to 8 years with single ventricle physiology who had the Fontan procedure within 4 months before enrollment.

In EINSTEIN-Jr, the efficacy and safety of rivaroxaban was assessed in 500 children aged from birth to 17 years with acute VTE who had received initial parenteral anticoagulant therapy. Patients were randomly assigned 2:1 to receive either body weight-adjusted dose of rivaroxaban (tablets or new oral suspension) to approximate a 20mg adult dose or standard of care (eg, low molecular weight heparin, subcutaneous fondaparinux, and/or oral vitamin K antagonist). 

Results from EINSTEIN-Jr showed that treatment with rivaroxaban had a similar low risk of recurrent VTE (1.2% vs 3.0%, respectively; hazard ratio [HR] 0.40; 95% CI, 0.11-1.41) and similar rates of clinically relevant bleeding (3.0% vs 1.9%, respectively; HR 1.58; 95% CI, 0.51-6.27) vs standard of care. Moreover, the composite of recurrent VTE and major bleeding occurred in 1.2% of the rivaroxaban arm vs 4.2% of the standard of care arm (HR 0.30; 95% CI, 0.08-0.93). There were no fatal VTE events reported in either treatment arm. There were also no major bleeding events reported in the rivaroxaban arm vs 2 major bleeding events in the standard of care arm.

“The filing of this application is an important step in helping to address the burden of blood clots and provide doctors with optimal body weight-based dosing options in pediatric patients,” said James List, MD, PhD, Global Therapeutic Area Head, Cardiovascular & Metabolism, Janssen Research & Development, LLC.

If approved, the dosing regimen for Xarelto would be based on body weight for pediatric patients using either tablets or a novel, oral suspension formulation which would be administered through a unique color-coded dosing device designed to minimize dosing errors.


  1. Janssen submits New Drug Application to U.S. FDA for Xarelto® (rivaroxaban) to help prevent and treat blood clots in pediatric patients. [press release]. Raritan, NJ: Janssen Pharmaceutical Companies of Johnson & Johnson; June 23, 2021. 
  2. Xarelto® (rivaroxaban) helps protect pediatric patients from blood clots in late-breaking phase 3 EINSTEIN-Jr study. [press release]. Raritan, NJ: Janssen Pharmaceutical Companies of Johnson & Johnson; July 8, 2019.