The Edoxaban Hokusai VTE PEDIATRICS Study: An open-label, multicenter, randomized study of edoxaban for pediatric venous thromboembolic disease.

Background Little evidence is available for treatment of pediatric venous thromboembolism (VTE). Large randomized controlled trials are challenging in children. Current antithrombotic agents have many limitations, including nonoral administration and frequent monitoring. Edoxaban is an oral direct inhibitor of factor Xa without need of monitoring. In adults with VTE, edoxaban has shown to be effective and safe. Objectives The Edoxaban Hokusai VTE PEDIATRICS Study is an open-label, randomized clinical trial to evaluate pharmacokinetics (PK) and pharmacodynamics (PD) of edoxaban and whether edoxaban is noninferior to standard of care in treatment of pediatric VTE. Methods A goal of 274 patients will be recruited in 5 age categories. A multidose PK/PD assessment on day 5 in the first 12 patients of each age group is incorporated into this study. The primary composite efficacy outcome comprises symptomatic recurrent VTE, death due to VTE, and no change or extension of thrombotic burden. The principal safety end point is a combination of major and clinically relevant nonmajor bleeding. PK end points include apparent systemic clearance and volume of distribution of edoxaban. PD end points include prothrombin time, activated partial thromboplastin time, and anti-factor Xa level for the edoxaban treatment arm. Results To increase feasibility, the multidose PK/PD study is integrated in the phase 3 trial. In addition, thrombotic burden, which is a prognostic factor for post thrombotic syndrome in children, is one of the components of the primary composite efficacy outcome. Conclusion This study will increase the level of evidence for treatment in pediatric VTE.