To date, there have been hardly any controlled clinical trials around the management of venous thromboembolism (VTE) in children. Most information has been extrapolated from adults, and applied to children, based on body weight. Dr. Christoph Male and colleagues sought out to compare the efficacy and safety of rivaroxaban with standard anticoagulants for treatment of acute VTE in children.
In the EINSTEIN-Jr. Phase III study, 500 children (from birth to 18 years of age) with acute VTE were randomized (2:1 ratio) to receive open-label rivaroxaban (tablets or suspension) in bodyweight-adjusted 20-mg equivalent dose regimens as compared with standard of care for the treatment of children with acute VTE. The main treatment period was 3 months (1 month in children < 2 years with catheter-related VTE). Symptomatic recurrent VTE and bleeding were centrally assessed unaware of treatment assignment. The first patient included was from Q4 of 2014, and the last patient last visit was in Q1 of 2019.
Dr. Male showed that recurrent VTE occurred in ~1% rivaroxaban-recipients and in 3.0% of comparator-recipients (hazard ratio 0.40, 95% confidence interval, 0.11 to 1.41). Repeat imaging showed an improved effect of rivaroxaban on thrombus resolution as compared with standard of care. Clinically relevant bleeding occurred in 3% of children with rivaroxaban, and in 1.9% children with comparator. Interestingly, the relative efficacy and safety estimates of rivaroxaban versus comparator were comparable to those obtained in adults which corroborates the findings in children. The pharmacokinetic (PK) parameters for rivaroxaban in children were equal to those achieved in adult VTE trials that showed efficacy of rivaroxaban.
As Male stated, “In the largest study done to date for treatment of VTE in children, our results demonstrated that rivaroxaban had a comparable efficacy and safety as in adults.”