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

Long Bin Jeng, Sung Gyu Lee, Arvinder Singh Soin, Wei Chen Lee, Kyung Suk Suh, Dong Jin Joo, Shinji Uemoto, Jaewon Joh, Tomoharu Yoshizumi, Horng Ren Yang, Gi Won Song, Patricia Lopez, Jossy Kochuparampil, Carole Sips, Shuhei Kaneko, Gary Levy

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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 m2, P =.108), and in patients continuing randomized treatment (−8.0 vs. −13.3 mL/min/1.73 m2, 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.

Original languageEnglish
Pages (from-to)1435-1446
Number of pages12
JournalAmerican Journal of Transplantation
Volume18
Issue number6
DOIs
Publication statusPublished - Jun 2018

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Efficacy and safety of everolimus with reduced tacrolimus in living-donor liver transplant recipients: 12-month results of a randomized multicenter study'. Together they form a unique fingerprint.

Cite this