Body weight-adjusted oral rivaroxaban is a possible treatment option for pediatric patients with venous thromboembolism (VTE), according to the EINSTEIN-Jr. study presented at the 2019 ASH Annual Meeting.
EINSTEIN-Jr. is a comprehensive clinical development program that seeks to provide data to support the use of rivaroxaban for children with VTE. Previous results from the phase III EINSTEIN-Jr. study showed similar safety and efficacy between rivaroxaban and standard anticoagulation for pediatric VTE. Updated results from the trial assessed the dose-exposure-response relationship with rivaroxaban.
Between November 2014 and September 2018, 365 patients received rivaroxaban; patients were categorized by weight: ≥30 kg, 12-30 kg, and <12 kg. Patients were also stratified based on age: birth to 0.5 years (n=13); 0.5 to one year (n=21); two to five years (n=44); six to 11 years (n=65); and 12 to 17 years (n=173). Most patients (n=316; 94.3%) were evaluable for pharmacokinetic (PK) analyses.
A total of 121 children (38.3%) received rivaroxaban tablet and 195 (61.7%) received a newly developed granules-for-oral suspension formulation. Symptomatic recurrent VTE occurred in two children (0.6%) during rivaroxaban treatment.
Repeat imaging outcomes in asymptomatic children were classified as normalized in 124 (39.2%), improved in 125 (39.6%), no relevant change in 16 (5.1%), and deteriorated in one (0.3%); for 48 children (15.2%), the imaging results were uncertain.
No major bleeding events occurred with rivaroxaban. Clinically relevant non-major bleeding and trivial bleeding were observed in 10 (3.2%) and 111 (35.1%) children, respectively.
Researchers observed no clustering for any of the PK parameters with respect to efficacy, bleeding, or adverse event outcomes. The results did not differ between the two treatment formulations.
“We conclude that the body weight-adjusted pediatric rivaroxaban regimens with either tablets or suspension are validated and provide a new alternative treatment option for VTE in children,” the researchers concluded.
Young G, Lensing AWA, Monagle P, et al. Rivaroxaban for treatment of pediatric venous thromboembolism. An Einstein-Jr phase 3 dose-exposure-response evaluation. Abstract 164. Presented at the 2019 ASH Annual Meeting, December 7, 2019; Orlando, Florida.