Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

Direkt zur Navigaton springen.
Direkt zum Inhalt springen.

Navigation/Suche

Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid Stoffw Microb

Young, G; Lensing, AWA; Monagle, P; Male, C; Thelen, K; Willmann, S; Palumbo, JS; Kumar, R; Nurmeev, I; Hege, K; Bajolle, F; Connor, P; Hooimeijer, HL; Torres, M; Chan, AKC; Kenet, G; Holzhauer, S; Santamaría, A; Amedro, P; Beyer-Westendorf, J; Martinelli, I; Massicotte, MP; Smith, WT; Berkowitz, SD; Schmidt, S; Price, V; Prins, MH; Kubitza, D; EINSTEIN-Jr. Phase 3 Investigators.
Rivaroxaban for treatment of pediatric venous thromboembolism. An Einstein-Jr phase 3 dose-exposure-response evaluation.
J Thromb Haemost. 2020; 18(7):1672-1685 Doi: 10.1111/jth.14813
Web of Science PubMed FullText FullText_MUG

Study Group Mitglieder der Med Uni Graz:: Grangl Gernot
Altmetrics:
Dimensions Citations:
Plum Analytics:
Scite (citation analytics):
Abstract:: Recently, the randomized EINSTEIN-Jr study showed similar efficacy and safety for rivaroxaban and standard anticoagulation for treatment of pediatric venous thromboembolism (VTE). The rivaroxaban dosing strategy was established based on phase 1 and 2 data in children and through pharmacokinetic (PK) modeling. Rivaroxaban treatment with tablets or the newly developed granules-for-oral suspension formulation was bodyweight-adjusted and administered once-daily, twice-daily, or thrice-daily for children with bodyweights of ≥30, ≥12 to <30, and <12 kg, respectively. Previously, these regimens were confirmed for children weighing ≥20 kg but only predicted in those <20 kg. Based on sparse blood sampling, the daily area under the plasma concentration-time curve [AUC_(0-24)ss ] and trough [C_trough,ss ] and maximum [C_max,ss ] steady-state plasma concentrations were derived using population PK modeling. Exposure-response graphs were generated to evaluate the potential relationship of individual PK parameters with recurrent VTE, repeat imaging outcomes, and bleeding or adverse events. A taste-and-texture questionnaire was collected for suspension-recipients. Of the 335 children (aged 0-17 years) allocated to rivaroxaban, 316 (94.3%) were evaluable for PK analyses. Rivaroxaban exposures were within the adult exposure range. No clustering was observed for any of the PK parameters with efficacy, bleeding, or adverse event outcomes. Results were similar for the tablet and suspension formulation. Acceptability and palatability of the suspension were favorable. Based on this analysis and the recently documented similar efficacy and safety of rivaroxaban compared with standard anticoagulation, we conclude that bodyweight-adjusted pediatric rivaroxaban regimens with either tablets or suspension are validated and provide for appropriate treatment of children with VTE. © 2020 International Society on Thrombosis and Haemostasis.
Find related publications in this database (Keywords): anticoagulation; bodyweight-adjusted dosing; pediatric patients; pharmacokinetics; rivaroxaban; suspension; venous thromboembolism