Dabigatran for Treatment and Secondary Prevention of Venous Thromboembolism in Pediatric Congenital Heart Disease.

Background: Congenital heart disease (CHD) is common in children and associated with greater risk of thrombotic complications. Management of these complications with standard-of-care treatment is suboptimal for these children.

Methods And Results: The effectiveness and safety of dabigatran were demonstrated in pivotal pediatric studies for the treatment of acute venous thromboembolism (VTE; NCT01895777) and secondary VTE prevention (NCT02197416).

Dabigatran in the treatment and secondary prophylaxis of venous thromboembolism in children with thrombophilia.

In the phase 2b/3 DIVERSITY trial, 3 months treatment with dabigatran was noninferior to standard of care (SOC) for acute venous thromboembolism (VTE) in children. In a single-arm, phase 3, secondary VTE prevention study, up to 12 months dabigatran use was associated with favorable safety. Dabigatran is approved by the European Medicines Agency and US Food and Drug Administration for pediatric indications.

Anticoagulant Effects of Dabigatran on Coagulation Laboratory Parameters in Pediatric Patients: Combined Data from Five Pediatric Clinical Trials.

Background:  Dabigatran etexilate, a direct oral thrombin inhibitor, is approved to treat venous thromboembolism (VTE) in both adults and children.

Objectives:  This population analysis characterized relationships between dabigatran total plasma concentrations and coagulation laboratory parameters (activated partial thromboplastin time [aPTT]; diluted thrombin time [dTT]; ecarin clotting time [ECT]).

Methods:  Data from three phase 2a and one single-arm and one randomized, comparative phase 2b/3 pediatric studies (measurements: aPTT 2,925 [ = 358]; dTT 2,348 [ = 324]; ECT 2,929 [ = 357]) were compared with adult data (5,740 aPTT, 3,472 dTT, 3,817 ECT measurements;  = 1,978).

Outcome of patients with relapsed or progressive Ewing sarcoma enrolled on cooperative group phase 2 clinical trials: A report from the Children's Oncology Group.

SevenChildren's Oncology Group phase 2 trials for patients with relapsed/progressive solid tumors were analyzed to estimate the event-free survival (EFS) for relapsed/progressive Ewing sarcoma. One hundred twenty-eight Ewing sarcoma patients were enrolled and 124 events occurred. The 6-month EFS was 12.

Pharmacokinetic modeling and simulation support for age- and weight-adjusted dosing of dabigatran etexilate in children with venous thromboembolism.

Background: Dabigatran etexilate (DE), a direct oral thrombin inhibitor, has been evaluated in children with venous thromboembolism (VTE) using oral solution, pellets, or capsules.

Objectives: This study evaluated DE pharmacokinetics (PK) in children with VTE and the appropriateness of a DE pediatric age- and weight-based dosing algorithm.

Patients/methods: A population PK model was fitted to data from four single-arm and one randomized, comparative pediatric VTE studies (358 children aged birth to <18 years; 2748 PK observations) and one healthy-adult study (32 males aged <40 years; 1523 PK observations) using nonlinear mixed-effects modeling.