Everolimus With Reduced Tacrolimus Improves Renal Function in De Novo Liver Transplant Recipients: A Randomized Controlled Trial

被引：253

作者：

De Simone, P. ^{[1
]}

Nevens, F. ^{[2
]}

De Carlis, L. ^{[3
]}

Metselaar, H. J. ^{[4
]}

Beckebaum, S. ^{[5
,6
]}

Saliba, F. ^{[7
]}

Jonas, S. ^{[8
]}

Sudan, D. ^{[9
]}

Fung, J. ^{[10
]}

Fischer, L. ^{[11
]}

Duvoux, C. ^{[12
]}

Chavin, K. D. ^{[13
]}

Koneru, B. ^{[14
]}

Huang, M. A. ^{[15
]}

Chapman, W. C. ^{[16
]}

Foltys, D. ^{[17
]}

Witte, S. ^{[18
]}

Jiang, H. ^{[19
]}

Hexham, J. M. ^{[19
]}

Junge, G. ^{[18
]}

机构：

[1] Azienda Osped Univ, Pisa, Italy

[2] Univ Hosp KU Leuven, Dept Hepatol, Louvain, Belgium

[3] Azienda Osped Niguarda Ca Granda, Hepatobiliary Surg & Liver Transplantat Unit, Milan, Italy

[4] Univ Rotterdam Hosp, Erasmus MC, Dept Gastroenterol & Hepatol, Rotterdam, Netherlands

[5] Univ Hosp Essen, Dept Gen Visceral & Transplantat Surg, Essen, Germany

[6] Univ Munster, Dept Transplant Med, Munster, Germany

[7] Univ Paris 11, Hop Paul Brousse, AP HP, Hepatobiliary Ctr, F-94804 Villejuif, France

[8] Univ Med Ctr Leipzig, Dept Visceral Transplantat Thorac & Vasc Surg, Leipzig, Germany

[9] Duke Univ, Med Ctr, Div Transplant Surg, Dept Gen Surg, Durham, NC USA

[10] Cleveland Clin, Transplantat Ctr, Cleveland, OH 44106 USA

[11] Univ Med Ctr Eppendorf, Dept Hepatobiliary Surg & Transplantat, Hamburg, Germany

[12] Hop Henri Mondor, AP HP, Liver Transplant Unit, F-94010 Creteil, France

[13] Med Univ S Carolina, Div Transplant Surg, Charleston, SC 29425 USA

[14] Univ Med & Dent New Jersey, Sch Med, Dept Surg, Newark, NJ 07103 USA

[15] Henry Ford Hosp, Dept Internal Med, Div Gastroenterol, Detroit, MI 48202 USA

[16] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA

[17] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Transplant Surg, Mainz, Germany

[18] Novartis Pharma AG, Basel, Switzerland

[19] Novartis Pharmaceut, E Hanover, NJ USA

来源：

AMERICAN JOURNAL OF TRANSPLANTATION | 2012年 / 12卷 / 11期

关键词：

Efficacy; everolimus; liver transplantation; reduced; tacrolimus; withdrawal; CHRONIC KIDNEY-DISEASE; GLOMERULAR-FILTRATION-RATE; SIROLIMUS-BASED IMMUNOSUPPRESSION; HEPATOCELLULAR-CARCINOMA; MYCOPHENOLATE-MOFETIL; CALCINEURIN INHIBITOR; DOSE TACROLIMUS; CONVERSION; COMPLICATIONS; METAANALYSIS;

D O I：

10.1111/j.1600-6143.2012.04212.x

中图分类号：

R61 [外科手术学];

学科分类号：

摘要：

In a prospective, multicenter, open-label study, de novo liver transplant patients were randomized at day 30 +/- 5 to (i) everolimus initiation with tacrolimus elimination (TAC Elimination) (ii) everolimus initiation with reduced-exposure tacrolimus (EVR+Reduced TAC) or (iii) standard-exposure tacrolimus (TAC Control). Randomization to TAC Elimination was terminated prematurely due to a higher rate of treated biopsy-proven acute rejection (tBPAR). EVR+Reduced TAC was noninferior to TAC Control for the primary efficacy endpoint (tBPAR, graft loss or death at 12 months posttransplantation): 6.7% versus 9.7% (-3.0%; 95% CI -8.7, 2.6%; p<0.001 for noninferiority [12% margin]). tBPAR occurred in 2.9% of EVR+Reduced TAC patients versus 7.0% of TAC Controls (p = 0.035). The change in adjusted estimated GFR from randomization to month 12 was superior with EVR+Reduced TAC versus TAC Control (difference 8.50 mL/min/1.73 m(2), 97.5% CI 3.74, 13.27 mL/min/1.73 m(2), p<0.001 for superiority). Drug discontinuation for adverse events occurred in 25.7% of EVR+Reduced TAC and 14.1% of TAC Controls (relative risk 1.82, 95% CI 1.25, 2.66). Relative risk of serious infections between the EVR+Reduced TAC group versus TAC Controls was 1.76 (95% CI 1.03, 3.00). Everolimus facilitates early tacrolimus minimization with comparable efficacy and superior renal function, compared to a standard tacrolimus exposure regimen 12 months after liver transplantation.

引用

页码：3008 / 3020

页数：13

共 35 条

[1] Use of Sirolimus in Liver Transplant Recipients with Renal Insufficiency: A Systematic Review and Meta-Analysis [J].