Purpose: This research was planned as a part of regulatory post marketing surveillance according to the Standard for Re-examination of New Drugs to reconfirm the safety and efficacy of everolimus (Certican®) combined with reduced Cyclosporine A (CsA) after renal transplantation, by investigating incidence of any serious adverse event and adverse event early (12 weeks) after administration.
Methods: This study involving 4 centers in Korea was performed from 17 Mar 2012 to 8 Oct 2013. In this prospective, open-label, multicenter, single-arm study, 54 patients were followed up for 12 weeks after administration of the study drug. The concentration of everolimus was adjusted to be 3-8 ng/ml. The concentration of CsA was adjusted to be 100-200 ng/ml till 4 weeks after then to be 75-150 ng/ml. The primary endpoints was incidence of serious adverse events and secondary endpoints was incidence of adverse events, presence or absence of acute rejection, and renal function were measured.
Results: Of 54 patients enrolled in the study, 1 patient (consent withdrawal) and 4 patients (other reasons) were withdrawn and 49 in total completed the study. The subjects of Intention to treat (ITT) analysis were 52. Forty nine (94.23%) of 52 patients reported 165 adverse events during the study period. The overall incidence of biopsy-proven acute rejection within 12 weeks after transplantation was 4 patients (7.69 %). A total of 17 serious adverse events were reported in 12 patients (23.08 %). The most frequent of serious adverse events were Urinary tract infection, Blood creatinine increased, Lymphocele (3.85 %) followed by Bronchopneumonia (1.92 %), Gastritis, Nephropathy toxic, Oliguria, Renal necrosis, Renal tubular disorder, Cerebral infarction, Convulsion, Compression fracture, and Transplant rejection (1.92 %). Of 17 serious adverse events reported this time, 5 cases (29.41 %) were serious adverse drug reactions whose causality to the study drug could not be ruled out. The most frequent serious adverse drug reactions was Lymphocele (3.85 %) (Table 1). The analysis of renal function in the ITT set showed mean e-GRF was 7.51 ± 3.06 mL/min/1.73m2 at Visit 1 (before transplantation), 71.66 ± 23.81 mL/min/1.73 m2 at Visit 3 (1 week), 70.54 ± 20.33 mL/min/1.73 m2 at Visit 4 (4 weeks) and 66.76 ± 18.08 mL/min/1.73 m2 at Visit 5 (12 weeks). Renal function (e-GFR) was decreased by 6.74 ± 20.27 mL/min/1.73 m2 with statistically significant difference (p=0.0242) at Visit 5 from Visit 3.
Conclusions: Compared with previous literature reports, there was no clinically significant finding in terms of safety and efficacy in this study. And further follow-up evaluation for renal function would be needed because it was not enough follow-up periods to get conclusion.