Rivaroxaban compared with standard anticoagulants for the treatment of acute venous thromboembolism in children: a randomised, controlled, phase 3 trial.
In this multicentre, parallel-group, open-label, randomised trial, the authors compared the efficacy and safety of rivaroxaban versus standard anticoagulants in children 0-17 years with venous thromboembolism. Across 107 paediatric hospitals in 28 countries, children with documented acute venous thromboembolism (VTE) who had started heparin were assigned (2:1) to weight-adjusted rivaroxaban or standard anticoagulants (heparin or switched to vitamin K antagonist).
Randomisation was stratified by age and VTE site. The main treatment period was 3 months (1 month in children <2 years of age with central venous catheter-related VTE). Primary efficacy outcomes were symptomatic recurrent VTE (assessed by intention-to-treat), and major or clinically relevant non-major bleeding.
500 (96%) of 520 eligible children were enrolled. After a median follow-up of 91 days (IQR 87-95) in children who had a study treatment period of 3 months (n = 463) and 31 days (IQR 29-35) in children who had a study treatment period of 1 month (n = 37), symptomatic recurrent VTE occurred in four (1%) of 335 children receiving rivaroxaban and five (3%) of 165 receiving standard anticoagulants (hazard ratio [HR] 0.40, 95% CI 0.11-1.41). Repeat imaging showed an improved effect of rivaroxaban on thrombotic burden as compared with standard anticoagulants (P = 0.012).
Major or clinically relevant non-major bleeding in participants who received ≥1 dose occurred in ten (3%) of 329 children (all non-major) receiving rivaroxaban and in three (2%) of 162 children (two major and one non-major) receiving standard anticoagulants (HR 1.58, 95% CI 0.51-6.27). Absolute and relative efficacy and safety estimates of rivaroxaban versus standard anticoagulation estimates were similar to those in rivaroxaban studies in adults. There were no treatment-related deaths.
In children with acute VTE, treatment with rivaroxaban resulted in a similarly low recurrence risk and reduced thrombotic burden without increased bleeding, as compared with standard anticoagulants.
– Jill M. Cholette (SABM reviewer)