Research has indicated that the incidence of venous thromboembolism (VTE) in hospitalized children has increased approximately 70% over a 6-year period and is thought to affect approximately 1 in every 200 hospitalized children. The rise in VTE is largely attributed to increased use of invasive support of critically ill patients—especially central venous access devices, which can lead to catheter-related VTE—and improved survival of patients with complex medical conditions. While there is experience with a diverse range of commercially available anti-thrombotic medications in the adult population, there is a relative paucity of data regarding the use of these agents in the pediatric population. Specifically, the current standard of care (SOC) for children with VTE includes initially heparins followed by vitamin K antagonists. Heparins require parenteral administration and frequent monitoring whereas Vitamin K antagonists require titration of the dose based on the INR. Dabigatran etexilate (DE) is a direct oral anticoagulant that does not require titration of its dose on adults. With these limitations in mind, Dr. Manuela Albisetti of Switzerland and co-workers sought to compare the safety and efficacy (recurrence of VTE, VTE-related death, and thrombus resolution) of the direct oral anticoagulant DE to SOC in the pediatric population, as well as the appropriateness of a DE dosing algorithm.
This phase IIb/III trial was an open-label, randomized, active-controlled, multicenter study of pediatric patients who had a confirmed VTE diagnosis and were initially treated with unfractionated heparin or low-molecular-weight heparin. Dr. Albisetti and co-workers randomized patients to DE or SOC and treated them for 3 months. The dose of DE was calculated by an age- and body weight-adjusted dosing algorithm. According to Dr. Albisetti, “We found that the number of children completing treatment who met the composite efficacy endpoint was similar, meaning that DE was non-inferior to SOC. In addition, the number of children who experienced major bleeding events comparable with SOC and DE. As such, we consider that DE has similar efficacy and safety to SOC in children with acute VTE.”
Importantly, Dr. Albisetti and co-workers found that it was appropriate to use the age- and body weight-adjusted dosing algorithm for DE in children less than 18 years of age. The DIVERSITY trial is the first of its kind to compare the direct oral anticoagulant DE to SOC, and provides valuable insight into the efficacy, safety, and pharmacokinetic-pharmacodynamic properties of DE in children with acute VTE.