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Impact of the early reduction of cyclosporine on renal function in heart transplant patients: a French randomised controlled trial

BACKGROUND: Using reduced doses of Cyclosporine A immediately after heart transplantation in clinical trials may suggest benefits for renal function by reducing serum creatinine levels without a significant change in clinical endpoints. However, these trials were not sufficiently powered to prove cl...

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Autores principales: Boissonnat, Pascale, Gaillard, Ségolène, Mercier, Catherine, Redonnet, Michel, Lelong, Bernard, Mattei, Marie-Françoise, Mouly-Bandini, Annick, Pattier, Sabine, Sirinelli, Agnès, Epailly, Eric, Varnous, Shaida, Billes, Marc-Alain, Sebbag, Laurent, Ecochard, René, Cornu, Catherine, Gueyffier, François
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3533735/
https://www.ncbi.nlm.nih.gov/pubmed/23206408
http://dx.doi.org/10.1186/1745-6215-13-231
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author Boissonnat, Pascale
Gaillard, Ségolène
Mercier, Catherine
Redonnet, Michel
Lelong, Bernard
Mattei, Marie-Françoise
Mouly-Bandini, Annick
Pattier, Sabine
Sirinelli, Agnès
Epailly, Eric
Varnous, Shaida
Billes, Marc-Alain
Sebbag, Laurent
Ecochard, René
Cornu, Catherine
Gueyffier, François
author_facet Boissonnat, Pascale
Gaillard, Ségolène
Mercier, Catherine
Redonnet, Michel
Lelong, Bernard
Mattei, Marie-Françoise
Mouly-Bandini, Annick
Pattier, Sabine
Sirinelli, Agnès
Epailly, Eric
Varnous, Shaida
Billes, Marc-Alain
Sebbag, Laurent
Ecochard, René
Cornu, Catherine
Gueyffier, François
author_sort Boissonnat, Pascale
collection PubMed
description BACKGROUND: Using reduced doses of Cyclosporine A immediately after heart transplantation in clinical trials may suggest benefits for renal function by reducing serum creatinine levels without a significant change in clinical endpoints. However, these trials were not sufficiently powered to prove clinical outcomes. METHODS: In a prospective, multicentre, open-label, parallel-group controlled trial, 95 patients aged 18 to 65 years old, undergoing de novo heart transplantation were centrally randomised to receive either a low (130 < trough CsA concentrations <200 μg/L, n = 47) or a standard dose of Cyclosporine A (200 < trough CsA concentrations <300 μg/L, n = 48) for the three first post-transplant months along with mycophenolate mofetil and corticosteroids. Participants had a stable haemodynamic status, a serum creatinine level <250 μmol/L and the donors’ cold ischemia time was under six hours; multiorgan transplants were excluded. The change in serum creatinine level over 12 months was used as the main criterion for renal function. Intention-to-treat analysis was performed on the 95 randomised patients and a mixed generalised linear model of covariance was applied. RESULTS: At 12 months, the mean (± SD) creatinine value was 120.7 μmol/L (± 35.8) in the low-dose group and 132.3 μmol/L (± 49.1) in the standard-dose group (P = 0.162). Post hoc analyses suggested that patients with higher creatinine levels at baseline benefited significantly from the lower Cyclosporine A target. The number of patients with at least one rejection episode was not significantly different but one patient in the low-dose group and six in the standard-dose group required dialysis. CONCLUSIONS: In patients with de novo cardiac transplantation, early Cyclosporine A dose reduction was not associated with renal benefit at 12 months. However, the strategy may benefit patients with high creatinine levels before transplantation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00159159
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spelling pubmed-35337352013-01-03 Impact of the early reduction of cyclosporine on renal function in heart transplant patients: a French randomised controlled trial Boissonnat, Pascale Gaillard, Ségolène Mercier, Catherine Redonnet, Michel Lelong, Bernard Mattei, Marie-Françoise Mouly-Bandini, Annick Pattier, Sabine Sirinelli, Agnès Epailly, Eric Varnous, Shaida Billes, Marc-Alain Sebbag, Laurent Ecochard, René Cornu, Catherine Gueyffier, François Trials Research BACKGROUND: Using reduced doses of Cyclosporine A immediately after heart transplantation in clinical trials may suggest benefits for renal function by reducing serum creatinine levels without a significant change in clinical endpoints. However, these trials were not sufficiently powered to prove clinical outcomes. METHODS: In a prospective, multicentre, open-label, parallel-group controlled trial, 95 patients aged 18 to 65 years old, undergoing de novo heart transplantation were centrally randomised to receive either a low (130 < trough CsA concentrations <200 μg/L, n = 47) or a standard dose of Cyclosporine A (200 < trough CsA concentrations <300 μg/L, n = 48) for the three first post-transplant months along with mycophenolate mofetil and corticosteroids. Participants had a stable haemodynamic status, a serum creatinine level <250 μmol/L and the donors’ cold ischemia time was under six hours; multiorgan transplants were excluded. The change in serum creatinine level over 12 months was used as the main criterion for renal function. Intention-to-treat analysis was performed on the 95 randomised patients and a mixed generalised linear model of covariance was applied. RESULTS: At 12 months, the mean (± SD) creatinine value was 120.7 μmol/L (± 35.8) in the low-dose group and 132.3 μmol/L (± 49.1) in the standard-dose group (P = 0.162). Post hoc analyses suggested that patients with higher creatinine levels at baseline benefited significantly from the lower Cyclosporine A target. The number of patients with at least one rejection episode was not significantly different but one patient in the low-dose group and six in the standard-dose group required dialysis. CONCLUSIONS: In patients with de novo cardiac transplantation, early Cyclosporine A dose reduction was not associated with renal benefit at 12 months. However, the strategy may benefit patients with high creatinine levels before transplantation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00159159 BioMed Central 2012-12-03 /pmc/articles/PMC3533735/ /pubmed/23206408 http://dx.doi.org/10.1186/1745-6215-13-231 Text en Copyright ©2012 Boissonnat et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Boissonnat, Pascale
Gaillard, Ségolène
Mercier, Catherine
Redonnet, Michel
Lelong, Bernard
Mattei, Marie-Françoise
Mouly-Bandini, Annick
Pattier, Sabine
Sirinelli, Agnès
Epailly, Eric
Varnous, Shaida
Billes, Marc-Alain
Sebbag, Laurent
Ecochard, René
Cornu, Catherine
Gueyffier, François
Impact of the early reduction of cyclosporine on renal function in heart transplant patients: a French randomised controlled trial
title Impact of the early reduction of cyclosporine on renal function in heart transplant patients: a French randomised controlled trial
title_full Impact of the early reduction of cyclosporine on renal function in heart transplant patients: a French randomised controlled trial
title_fullStr Impact of the early reduction of cyclosporine on renal function in heart transplant patients: a French randomised controlled trial
title_full_unstemmed Impact of the early reduction of cyclosporine on renal function in heart transplant patients: a French randomised controlled trial
title_short Impact of the early reduction of cyclosporine on renal function in heart transplant patients: a French randomised controlled trial
title_sort impact of the early reduction of cyclosporine on renal function in heart transplant patients: a french randomised controlled trial
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3533735/
https://www.ncbi.nlm.nih.gov/pubmed/23206408
http://dx.doi.org/10.1186/1745-6215-13-231
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