부산대학교 도서관

Background:The TEAMMATE Trial is the first randomized clinical trial in pediatric heart transplantation (HT) and compares outcomes in children randomized to everolimus (EVL) vs. tacrolimus as the primary immunosuppressant. The initial dosing strategy for everolimus has not been evaluated in pediatric HT patients.Methods:Children newly randomized to EVL in the TEAMMATE Trial at 6 months post-HT were analyzed to determine how effective the initial dosing strategy (1.4 mg/m2/day rounded to the nearest 0.25 mg; Table) was in achieving a therapeutic EVL level (3-8 ng/mL). The primary endpoint was time to the therapeutic range (TTR) defined as the time between the first dose of EVL and the first therapeutic EVL level. Secondary endpoints included the proportion of patients who achieved a therapeutic level using the initial EVL dose, and the dose required to achieve a steady-state level.Results:Among 53 children studied, the median age at HT was 4.3 years (IQR, 0.6, 12.5); 36% had a transplant for congenital heart disease (CHD); at randomization, median weight was 17.1 kg (8.5, 34.6) and GFR was 119?30 mL/kg/1.73m2. Over half (n=29, 55%) received EVL in tablet form; 24 (45%) as liquid preparation. During the study, 51 (96%) of the patients achieved a therapeutic EVL level with a median TTR of 10 days (6, 24): 16 days (5.5, 30) in the tablet group and 9 days (6, 13) in the liquid preparation group (P=0.14). The steady state dose of EVL was equal to the initial dose of EVL in 45% of the patients who achieved a therapeutic level. The median steady state dose of EVL to achieve the therapeutic level was 1.6 mg/m2/day (range 0.7-8.0; IQR, 1.3, 2.6).Conclusion:The everolimus dosing strategy used in the TEAMMATE Trial appears to be working well with most children reaching the therapeutic EVL level within two weeks. Patients receiving liquid preparation of EVL achieved goal levels at least as quickly as patients receiving tablets. A therapeutic EVL level was achieved with a median dose of 1.6 mg/m2/day.