Journal article
Systematic review on the design and methodology of the pediatric direct oral anticoagulant clinical trials for thrombosis prevention: Communication from the ISTH SSC Subcommittee on Pediatric and Neonatal Thrombosis and Hemostasis
Journal of thrombosis and haemostasis
03/20/2026
DOI: 10.1016/j.jtha.2026.03.011
PMID: 41865887
Abstract
Prevention of thromboembolism (TE) remains a priority in children with a high thrombotic risk. While recent trials using direct oral anticoagulants (DOACs) for TE prevention have been completed, these trials had significant limitations.
To review the methodology of pediatric DOAC trials for TE prevention to identify design and execution challenges and opportunities for improvement.
We performed a systematic review of MEDLINE, EMBASE, the Cochrane Library, and clinicaltrials.gov, from January 2002 to April 2025, to identify pediatric trials evaluating DOACs for TE prevention. We compared registered information in clinicaltrials.gov, trial design manuscripts, and final result manuscripts of pivotal TE prevention DOAC trials to highlight changes in methods, study duration, and outcomes.
Eight publications from four trials, one design and one final manuscript each, were included. Each trial targeted a pediatric subpopulation: three in cardiac disease and one in oncology. Together, 984 children enrolled in the four trials. All trials had some modification to methdology from original design, including changes in eligibility criteria, sample size, timing of endpoint ascertainment, outcomes, and analysis. All but one required a longer duration to complete than planned. Only one trial had definitive statistical power calculations.
The pediatric DOAC trials for TE prevention provide an opportunity to understand the unique successes and limitations in studying TE prevention in children. Given lack of power, inconsistent definitions, and limited follow-up duration, questions remain regarding safety, dose intensity, endpoints, and appropriate selection of high-risk populations. Future research should employ innovative methods to overcome these limitations.
Details
- Title: Subtitle
- Systematic review on the design and methodology of the pediatric direct oral anticoagulant clinical trials for thrombosis prevention: Communication from the ISTH SSC Subcommittee on Pediatric and Neonatal Thrombosis and Hemostasis
- Creators
- Hilary Whitworth - Children's Hospital of PhiladelphiaMarisol Betensky - Johns Hopkins UniversityRukhmi V Bhat - Lurie Children's HospitalMaha Al-Ghafry - Johns Hopkins UniversityErnest K Amankwah - Johns Hopkins UniversityTina T Biss - Newcastle upon Tyne Hospitals NHS Foundation TrustLeonardo Brandao - Hospital for Sick ChildrenAnthony Chan - McMaster Children's HospitalSusanne Holzhauer - Charité - Universitätsmedizin BerlinAmy L Kiskaddon - Johns Hopkins UniversityIrene L M Klaassen - Emma KinderziekenhuisPaul Monagle - Royal Children's HospitalLeslie Raffini - Children's Hospital of PhiladelphiaShoshana Revel-Vilk - Shaare Zedek Medical CenterAnjali Sharathkumar - University of IowaAnthony A Sochet - Johns Hopkins All Children's HospitalC Heleen van Ommen - Erasmus MCChristoph Male - Medical University of ViennaNeil A Goldenberg - Johns Hopkins University
- Resource Type
- Journal article
- Publication Details
- Journal of thrombosis and haemostasis
- DOI
- 10.1016/j.jtha.2026.03.011
- PMID
- 41865887
- NLM abbreviation
- J Thromb Haemost
- ISSN
- 1538-7836
- eISSN
- 1538-7836
- Publisher
- Elsevier
- Language
- English
- Electronic publication date
- 03/20/2026
- Academic Unit
- Stead Family Department of Pediatrics; Hematology/Oncology
- Record Identifier
- 9985144719302771
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