Efficacy and safety of everolimus with reduced tacrolimus in living-donor liver transplant recipients: 12-month results of a randomized multicenter study.

Autor:	Jeng LB; China Medical University Hospital, Taichung, Taiwan., Lee SG; Asan Medical Center, Seoul, Republic of Korea., Soin AS; Medanta, Medicity Hospital, Gurgaon, India., Lee WC; Chang Gung Memorial Hospital, Tao-Yuan, Lin-Ko, Taiwan., Suh KS; Seoul National University College of Medicine, Seoul, Republic of Korea., Joo DJ; Yonsei University College of Medicine, Severance Hospital, Seoul, Republic of Korea., Uemoto S; Kyoto University Hospital, Kyoto, Japan., Joh J; Samsung Medical Center, Seoul, Republic of Korea., Yoshizumi T; Kyushu University Hospital, Fukuoka-city, Japan., Yang HR; China Medical University Hospital, Taichung, Taiwan., Song GW; Asan Medical Center, Seoul, Republic of Korea., Lopez P; Novartis Pharma AG, Basel, Switzerland., Kochuparampil J; Novartis Pharma AG, Basel, Switzerland., Sips C; Novartis Pharma AG, Basel, Switzerland., Kaneko S; Novartis Pharma KK, Tokyo, Japan., Levy G; University of Toronto, Toronto, Canada.
Jazyk:	angličtina
Zdroj:	American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons [Am J Transplant] 2018 Jun; Vol. 18 (6), pp. 1435-1446. Date of Electronic Publication: 2018 Jan 25.
DOI:	10.1111/ajt.14623
Abstrakt:	In a multicenter, open-label, study, 284 living-donor liver transplant patients were randomized at 30 ± 5 days posttransplant to start everolimus+reduced tacrolimus (EVR+rTAC) or continue standard tacrolimus (TAC Control). EVR+rTAC was non-inferior to TAC Control for the primary efficacy endpoint of treated BPAR, graft loss or death at 12 months posttransplant: difference -0.7% (90% CI -5.2%, 3.7%); P < .001 for non-inferiority. Treated BPAR occurred in 2.2% and 3.6% of patients, respectively. The key secondary endpoint, change in estimated glomerular filtration rate (eGFR) from randomization to month 12, achieved non-inferiority (P < .001 for non-inferiority), but not superiority and was similar between groups overall (mean -8.0 vs. -12.1 mL/min/1.73 m 2 , P = .108), and in patients continuing randomized treatment (-8.0 vs. -13.3 mL/min/1.73 m 2 , P = .046). In the EVR+rTAC and TAC control groups, study drug was discontinued in 15.5% and 17.6% of patients, adverse events with suspected relation to study drug occurred in 57.0% and 40.4%, and proteinuria ≥1 g/24 h in 9.3% and 0%, respectively. Everolimus did not negatively affect liver regeneration. At 12 months, hepatocellular recurrence was only seen in the standard TAC-treated patients (5/62; 8.1%). In conclusion, early introduction of EVR+rTAC was non-inferior to standard tacrolimus in terms of efficacy and renal function at 12 months, with hepatocellular carcinoma recurrence only in TAC Control patients. ClinicalTrials.gov Identifier: NCT01888432. (© 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.)
Databáze:	MEDLINE
Externí odkaz:	Plný text