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. 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 the DIVERSITY trial and safety in both studies.
Thrombophilia types were similar between the DIVERSITY trial (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%; and
antiphospholipid antibodies, 18% vs 20% of patients, respectively. In DIVERSITY, 36% and 22% of
thrombophilia subgroup patients treated with
dabigatran and SOC, respectively, met the primary end point (Mantel-Haenszel-weighted rate difference, -0.135; 95% confidence interval, -0.36 to 0.08; noninferiority P = .0014); comparable to the total DIVERSITY trial population (46% vs 42%) showing
dabigatran noninferiority 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. These trials were registered at www.clinicaltrials.gov as #NCT01895777 and #NCT02197416.