Dabigatran in the treatment and secondary prophylaxis of venous thromboembolism in children with thrombophilia.
washington; spokane; pshmc
In the phase 2b/3 DIVERSITY trial (NCT01895777), 3 months' treatment with dabigatran was non-inferior to standard of care (SOC) for acute venous thromboembolism (VTE) in children. In a single-arm phase 3 secondary VTE prevention study (NCT02197416), up to 12 months' dabigatran was associated with favorable safety. Dabigatran is approved by the European Medicines Agency and US Food and Drug Administration for pediatric indications. We assessed primary composite efficacy (complete thrombus resolution and freedom from VTE recurrence/VTE-related death) in subgroups with thrombophilia vs those with negative/unknown thrombophilia status in DIVERSITY and safety in both studies. Thrombophilia types were similar between DIVERSITY (total population) and secondary prevention studies: factor-V-Leiden, 42% vs 33%; prothrombin mutation G20210A, 19% vs 17%; antithrombin deficiency, 15% vs 20%; protein C/S deficiency, 23% vs 25%; antiphospholipid antibodies, 18% vs 20% patients, respectively. In DIVERSITY, 36% and 22% of thrombophilia subgroup patients treated with dabigatran and SOC, respectively, met the primary endpoint (Mantel-Haenszel-weighted rate difference -0.135 [95% CI-0.36, 0.08], non-inferiority P = .0014); comparable to the total DIVERSITY population (46% vs 42%) showing dabigatran non-inferiority to SOC. Within this subgroup, numerically fewer patients experienced VTE recurrence or progression of index thrombus in the dabigatran-treatment group vs SOC. In the secondary prevention study, VTE recurrence at 12 months occurred in 2.8% of patients with thrombophilia vs 0% with negative/unknown thrombophilia. Safety profiles were consistent with those reported previously. Although they should be interpreted with caution, these exploratory findings suggest dabigatran could be an appropriate long-term anticoagulant for children with thrombophilia.
Women & Children
Brandão, Leonardo R; Tartakovsky, Igor; Albisetti, Manuela; Halton, Jacqueline Ml; Bomgaars, Lisa; Chalmers, Elizabeth; Luciani, Matteo; Saracco, Paola; Felgenhauer, Judy; Lvova, Olga; Simetzberger, Monika; Sun, Zhichao; and Mitchell, Lesley G, "Dabigatran in the treatment and secondary prophylaxis of venous thromboembolism in children with thrombophilia." (2022). Articles, Abstracts, and Reports. 6542.