A recent analysis suggests that dabigatran treatment resulted in similar coagulation patterns with increased concentration of the agent in both pediatric and adult patient populations. Findings of this analysis were reported in the journal Thrombosis and Haemostasis.
Dabigatran etexilate is approved as treatment for acute venous thromboembolism (VTE) and prevention of recurrent VTE in adult and pediatric patients. In this study, the researchers aimed to evaluate relationships between dabigatran plasma concentrations and laboratory coagulation parameters by age group.
There were 5 studies included in this analysis evaluating the use of dabigatran in pediatric patients with VTE. These included 3 phase 2a studies (ClinicalTrials.gov Identifiers: NCT00844415, NCT01083732, NCT02223260), 2 phase 2b/3 studies, as well as a single-arm study (ClinicalTrials.gov Identifier: NCT02197416), and the open-label, randomized, comparative DIVERSITY study (ClinicalTrials.gov Identifier: NCT01895777).
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A total of 4 studies involving the use of dabigatran in adult patients were evaluated for comparisons, 2 of which were phase 1 studies (ClinicalTrials.gov Identifiers: NCT01688830, NCT01955720), while 2 were phase 3 studies (ClinicalTrials.gov Identifiers: NCT00291330, and NCT00657150).
Data from clotting assays were used to evaluate total plasma concentrations of dabigatran in comparison with activated partial thromboplastin time (aPTT), diluted thrombin time (dTT), and ecarin clotting time (ECT). Across the evaluated studies, data were available from 358 children and 1978 adults, with varying numbers of patients and observations included within aPTT, dTT, and ECT analyses.
Patients younger than 6 months of age more often showed aPTT and ECT values that were near to, or beyond, the upper ranges for healthy adults. Patients younger than 6 months of age had a mean baseline aPTT of 44.8 seconds, and a mean baseline ECT of 39.9 seconds, compared with 36.1 and 36.4 seconds, respectively, in older children. However, dTT did not show patterns with age.
Dabigatran concentrations were associated with patterns of aPTT, dTT, and ECT measurements that were similar between pediatric and adult patients. As the dabigatran concentration rose, so did the aPTT, in a nonlinear fashion. Linear increases in dTT and ECT were seen with higher dabigatran concentrations.
“For the relationships between dabigatran and the laboratory coagulation parameters, there were either no, or small, age-related differences across pediatric age groups, and between children and adults (both healthy and/or patients), apart from baseline differences,” the researchers wrote in their report, also noting that age-related differences were seen only in aPTT and ECT measurements at baseline. For patients younger than 6 months, the researchers indicated longer clotting times at baseline are not incongruent with developmental hemostatic changes occurring during this time.
“Based on this analysis and clinical data showing the efficacy and safety of dabigatran in the pediatric VTE setting, the use of an age- and weight-adjusted dabigatran dosing algorithm to target adult dabigatran exposure is appropriate in children with VTE,” the researchers concluded in their report. They considered dTT to be the most reliable metric for evaluating dabigatran concentration.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Reference
Mitchel LG, Röshammar D, Huang F, et al. Anticoagulant effects of dabigatran on coagulation laboratory parameters in pediatric patients: combined data from five pediatric clinical trials. Thromb Haemost. Published online July 31, 2022. doi:10.1055/s-0042-1744542
