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Rivaroxaban for treatment of pediatric venous thromboembolism: An Einstein-Jr phase 3 dose-exposure-response evaluation

Rivaroxaban for treatment of pediatric venous thromboembolism: An Einstein-Jr phase 3 dose-exposure-response evaluation

Authors :
Ida Martinelli
Kirstin Thelen
Riten Kumar
Ildar Nurmeev
Anthony K.C. Chan
Susanne Holzhauer
Helene L. Hooimeijer
Victoria E. Price
Christoph Male
Marcela Torres
Guy Young
Kerry Hege
Scott D. Berkowitz
Philip Connor
Gili Kenet
Joseph S. Palumbo
M. Patricia Massicotte
William T. Smith
Stephan Schmidt
Stefan Willmann
Pascal Amedro
Dagmar Kubitza
Martin H. Prins
Paul Monagle
Fanny Bajolle
Amparo Santamaría
Jan Beyer-Westendorf
Anthonie W. A. Lensing
RS: CAPHRI - R5 - Optimising Patient Care
Epidemiologie
MUMC+: KIO Kemta (9)
Pediatrics
Medizinische Universität Wien = Medical University of Vienna
Université Paris Descartes - Paris 5 (UPD5)
CHU Necker - Enfants Malades [AP-HP]
Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp)
Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
King‘s College London
University of York [York, UK]
Helmut Schmidt University [Hamburg]
Source :
Journal of Thrombosis and Haemostasis, 18(7), 1672-1685. Wiley, Journal of Thrombosis and Haemostasis, 18(7), 1672-1685. Wiley-Blackwell Publishing Ltd, Journal of Thrombosis and Haemostasis, Journal of Thrombosis and Haemostasis, Wiley, 2020, 18 (7), pp.1672-1685. ⟨10.1111/jth.14813⟩
Publication Year :
2020

Abstract

Background: 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. Methods: 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 (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. Results: 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. Discussion: 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.

Details

Language :
English
ISSN :
15387933 and 15387836
Database :
OpenAIRE
Journal :
Journal of Thrombosis and Haemostasis, 18(7), 1672-1685. Wiley, Journal of Thrombosis and Haemostasis, 18(7), 1672-1685. Wiley-Blackwell Publishing Ltd, Journal of Thrombosis and Haemostasis, Journal of Thrombosis and Haemostasis, Wiley, 2020, 18 (7), pp.1672-1685. ⟨10.1111/jth.14813⟩
Accession number :
edsair.doi.dedup.....9bb33de5b932faaa8296a766f914b6f7
Full Text :
https://doi.org/10.1111/jth.14813⟩