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Everolimus With Reduced Tacrolimus Improves Renal Function in De Novo Liver Transplant Recipients: A Randomized Controlled Trial
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 tacrolimu...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Inc
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3533764/ https://www.ncbi.nlm.nih.gov/pubmed/22882750 http://dx.doi.org/10.1111/j.1600-6143.2012.04212.x |
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author | De Simone, P Nevens, F De Carlis, L Metselaar, H J Beckebaum, S Saliba, F Jonas, S Sudan, D Fung, J Fischer, L Duvoux, C Chavin, K D Koneru, B Huang, M A Chapman, W C Foltys, D Witte, S Jiang, H Hexham, J M Junge, G |
author_facet | De Simone, P Nevens, F De Carlis, L Metselaar, H J Beckebaum, S Saliba, F Jonas, S Sudan, D Fung, J Fischer, L Duvoux, C Chavin, K D Koneru, B Huang, M A Chapman, W C Foltys, D Witte, S Jiang, H Hexham, J M Junge, G |
author_sort | De Simone, P |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3533764 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Blackwell Publishing Inc |
record_format | MEDLINE/PubMed |
spelling | pubmed-35337642013-01-08 Everolimus With Reduced Tacrolimus Improves Renal Function in De Novo Liver Transplant Recipients: A Randomized Controlled Trial De Simone, P Nevens, F De Carlis, L Metselaar, H J Beckebaum, S Saliba, F Jonas, S Sudan, D Fung, J Fischer, L Duvoux, C Chavin, K D Koneru, B Huang, M A Chapman, W C Foltys, D Witte, S Jiang, H Hexham, J M Junge, G Am J Transplant Original Articles 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. Blackwell Publishing Inc 2012-11 /pmc/articles/PMC3533764/ /pubmed/22882750 http://dx.doi.org/10.1111/j.1600-6143.2012.04212.x Text en © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation. |
spellingShingle | Original Articles De Simone, P Nevens, F De Carlis, L Metselaar, H J Beckebaum, S Saliba, F Jonas, S Sudan, D Fung, J Fischer, L Duvoux, C Chavin, K D Koneru, B Huang, M A Chapman, W C Foltys, D Witte, S Jiang, H Hexham, J M Junge, G Everolimus With Reduced Tacrolimus Improves Renal Function in De Novo Liver Transplant Recipients: A Randomized Controlled Trial |
title | Everolimus With Reduced Tacrolimus Improves Renal Function in De Novo Liver Transplant Recipients: A Randomized Controlled Trial |
title_full | Everolimus With Reduced Tacrolimus Improves Renal Function in De Novo Liver Transplant Recipients: A Randomized Controlled Trial |
title_fullStr | Everolimus With Reduced Tacrolimus Improves Renal Function in De Novo Liver Transplant Recipients: A Randomized Controlled Trial |
title_full_unstemmed | Everolimus With Reduced Tacrolimus Improves Renal Function in De Novo Liver Transplant Recipients: A Randomized Controlled Trial |
title_short | Everolimus With Reduced Tacrolimus Improves Renal Function in De Novo Liver Transplant Recipients: A Randomized Controlled Trial |
title_sort | everolimus with reduced tacrolimus improves renal function in de novo liver transplant recipients: a randomized controlled trial |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3533764/ https://www.ncbi.nlm.nih.gov/pubmed/22882750 http://dx.doi.org/10.1111/j.1600-6143.2012.04212.x |
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