Open AccessDesign and rationale for the DIVERSITY study: An open‐label, randomized study of dabigatran etexilate for pediatric venous thromboembolism
Author(s) -
Albisetti Manuela,
Biss Branislav,
Bomgaars Lisa,
Brandão Leonardo R.,
Brueckmann Martina,
Chalmers Elizabeth,
Gropper Savion,
Harper Ruth,
Huang Fenglei,
Luciani Matteo,
Manastirski Ivan,
Mitchell Lesley G.,
Tartakovsky Igor,
Wang Bushi,
Halton Jacqueline M. L.
Publication year - 2018
Publication title -
research and practice in thrombosis and haemostasis
Language(s) - English
Resource type - Journals
ISSN - 2475-0379
DOI - 10.1002/rth2.12086
Subject(s) - medicine , dosing , dabigatran , venous thromboembolism , heparin , randomized controlled trial , intensive care medicine , low molecular weight heparin , clinical trial , surgery , warfarin , thrombosis , atrial fibrillation
Essentials 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.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 II b/ 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: NCT 01895777.