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Thrombosis Journal
Published in: Thrombosis Journal 1/2018

Open Access 01-12-2018 | Research

Rivaroxaban versus standard anticoagulation for acute venous thromboembolism in childhood. Design of the EINSTEIN-Jr phase III study

Authors: Anthonie W. A. Lensing, Christoph Male, Guy Young, Dagmar Kubitza, Gili Kenet, M. Patricia Massicotte, Anthony Chan, Angelo C. Molinari, Ulrike Nowak-Goettl, Ákos F. Pap, Ivet Adalbo, William T. Smith, Amy Mason, Kirstin Thelen, Scott D. Berkowitz, Mark Crowther, Stephan Schmidt, Victoria Price, Martin H. Prins, Paul Monagle

Published in: Thrombosis Journal | Issue 1/2018

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Abstract

Background

Venous thromboembolism (VTE) is a relatively rare condition in childhood with treatment mainly based on extrapolation from studies in adults. Therefore, clinical trials of anticoagulation in children require novel approaches to deal with numerous challenges. The EINSTEIN-Jr program identified pediatric rivaroxaban regimens commencing with in vitro dose finding studies followed by evaluation of children of different ages through phase I and II studies using extensive modeling to determine bodyweight-related doses. Use of this approach resulted in drug exposure similar to that observed in young adults treated with rivaroxaban 20 mg once-daily.

Methods

EINSTEIN-Jr phase III is a randomized, open-label, study comparing the efficacy and safety of rivaroxaban 20 mg-equivalent dose regimens with those of standard anticoagulation for the treatment of any types of acute VTE in children aged 0–18 years.
A total of approximately 500 children are expected to be included during the 4-year study window. Flexibility of treatment duration is allowed with study treatment to be given for 3 months with the option to continue treatment in 3-month increments, up to a total of 12 months. However, based on most common current practice, children younger than 2 years with catheter-related thrombosis will have a main treatment period of 1 month with the option to prolong treatment in 1-month increments, up to a total of 3 months.

Conclusions

EINSTEIN-Jr will compare previously established 20 mg-equivalent rivaroxaban dosing regimens with standard anticoagulation for the treatment of VTE in children. Demonstration of similarity of disease, as well as equivalent rivaroxaban exposure and exposure-response will enable extrapolation of efficacy from adult trials, which is critical given the challenges of enrollment in pediatric anticoagulation trials.

Trial registration

Clinicaltrials.gov NCT02234843, registered on 9 September 2014.
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Metadata
Title
Rivaroxaban versus standard anticoagulation for acute venous thromboembolism in childhood. Design of the EINSTEIN-Jr phase III study
Authors
Anthonie W. A. Lensing
Christoph Male
Guy Young
Dagmar Kubitza
Gili Kenet
M. Patricia Massicotte
Anthony Chan
Angelo C. Molinari
Ulrike Nowak-Goettl
Ákos F. Pap
Ivet Adalbo
William T. Smith
Amy Mason
Kirstin Thelen
Scott D. Berkowitz
Mark Crowther
Stephan Schmidt
Victoria Price
Martin H. Prins
Paul Monagle
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Thrombosis Journal / Issue 1/2018
Electronic ISSN: 1477-9560
DOI
https://doi.org/10.1186/s12959-018-0188-y

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