Design and rationale for the DIVERSITY study: An open‐label, randomized study of dabigatran etexilate for pediatric venous thromboembolism

Unlabelled Box •Current standard of care (SOC) for pediatric venous thromboembolism (VTE) has limitations. •Dabigatran etexilate (DE) versus SOC will be studied in children with VTE in a phase IIb/III trial. •A dosing algorithm for DE in children will be assessed guiding dosing. •Valuable data on the safety and efficacy of DE for VTE in children will be obtained. All authors have had full access to data and contributed to drafting of paper. Boehringer Ingelheim Pharma GmbH & Co. KG Boehringer Ingelheim Background The current standard of care (SOC) for pediatric venous thromboembolism (VTE) comprises unfractionated heparin (UFH), or low‐molecular‐weight heparin (LMWH) followed by LMWH or vitamin K antagonists, all of which have limitations. Dabigatran etexilate (DE) has demonstrated efficacy and safety for adult VTE and has the potential to overcome some of the limitations of the current SOC. Pediatric trials are needed to establish dosing in children and to confirm that results obtained in adults are applicable in the pediatric setting. Objectives To describe the design and rationale of a planned phase IIb/III trial that will evaluate a proposed dosing algorithm for DE and assess the safety and efficacy of DE versus SOC for pediatric VTE treatment. Patients/Methods An open‐label, randomized, parallel‐group noninferiority study will be conducted in approximately 180 patients aged 0 to <18 years with VTE, who have received initial UFH or LMWH treatment and who are expected to require ≥3 months of anticoagulation therapy. Patients will receive DE or SOC for 3 months. DE will be administered twice daily as capsules, pellets, or an oral liquid formulation according to patient age. Initial doses will be calculated using a proposed dosing algorithm. Results There will be two coprimary endpoints: a composite efficacy endpoint comprising the proportion of patients with complete thrombus resolution, freedom from recurrent VTE and VTE‐related mortality, and a safety endpoint: freedom from major bleeding events. Conclusion Findings will provide valuable information regarding the efficacy and safety of DE for the treatment of pediatric VTE. ClinicalTrials.gov registration number: NCT01895777.