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OSAKA Trial: A Randomized, Controlled Trial Comparing Tacrolimus QD and BD in Kidney Transplantation

BACKGROUND: The once-daily (QD), prolonged-release formulation of tacrolimus has been shown to improve adherence versus twice-daily (BD) tacrolimus. Treatment nonadherence in transplant recipients has been associated with poor graft outcomes. METHODS: This open-label, parallel-group study randomized...

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Autores principales: Albano, Laetitia, Banas, Bernhard, Klempnauer, Juergen L., Glyda, Maciej, Viklicky, Ondrej, Kamar, Nassim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3864174/
https://www.ncbi.nlm.nih.gov/pubmed/23982340
http://dx.doi.org/10.1097/TP.0b013e3182a203bd
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author Albano, Laetitia
Banas, Bernhard
Klempnauer, Juergen L.
Glyda, Maciej
Viklicky, Ondrej
Kamar, Nassim
author_facet Albano, Laetitia
Banas, Bernhard
Klempnauer, Juergen L.
Glyda, Maciej
Viklicky, Ondrej
Kamar, Nassim
author_sort Albano, Laetitia
collection PubMed
description BACKGROUND: The once-daily (QD), prolonged-release formulation of tacrolimus has been shown to improve adherence versus twice-daily (BD) tacrolimus. Treatment nonadherence in transplant recipients has been associated with poor graft outcomes. METHODS: This open-label, parallel-group study randomized adults with end-stage renal disease undergoing primary kidney transplantation or retransplantation to an initial dose of tacrolimus BD 0.2 mg/kg per day (Arm 1; n=309), QD 0.2 mg/kg per day (Arm 2; n=302), QD 0.3 mg/kg per day (Arm 3; n=304) all with mycophenolate mofetil and corticosteroids (tapered) over 24 weeks, or tacrolimus QD 0.2 mg/kg per day with mycophenolate mofetil, basiliximab, and corticosteroids given only perioperatively (Arm 4; n=283). The primary composite endpoint (efficacy failure; per protocol set) was defined as graft loss, biopsy-confirmed acute rejection, or graft dysfunction at week 24. Graft dysfunction was defined as estimated glomerular filtration rate Modification of Diet in Renal Disease-4 formula of less than 40 mL/min/1.73 m(2). The prespecified noninferiority margin was 12.5%. RESULTS: The per protocol set included 976 patients: 237, 263, 246, and 230 patients in Arms 1 to 4, respectively. Noninferiority of the composite endpoint was demonstrated for Arm 2 versus Arm 1; Kaplan–Meier estimates of efficacy failure were 42.2% and 40.6%, respectively (difference, −1.6%; 95% confidence interval [CI], −12.2% to 9.0%). Noninferiority to Arm 1 was not confirmed for Arm 3 (difference, −3.5%; 95% CI, −13.6% to 6.6%) or Arm 4 (difference, −7.1%; 95% CI, −16.1% to 1.9%). Graft dysfunction (estimated glomerular filtration rate <40 mL/min/1.73 m(2)) was the main determinant of composite-endpoint efficacy failure across all arms. CONCLUSIONS: In patients representative of the European kidney transplant population, tacrolimus QD-based immunosuppression (0.2 mg/kg/day), without induction, showed similar efficacy to 0.2 mg/kg per day tacrolimus BD.
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spelling pubmed-38641742013-12-16 OSAKA Trial: A Randomized, Controlled Trial Comparing Tacrolimus QD and BD in Kidney Transplantation Albano, Laetitia Banas, Bernhard Klempnauer, Juergen L. Glyda, Maciej Viklicky, Ondrej Kamar, Nassim Transplantation Clinical and Translational Research BACKGROUND: The once-daily (QD), prolonged-release formulation of tacrolimus has been shown to improve adherence versus twice-daily (BD) tacrolimus. Treatment nonadherence in transplant recipients has been associated with poor graft outcomes. METHODS: This open-label, parallel-group study randomized adults with end-stage renal disease undergoing primary kidney transplantation or retransplantation to an initial dose of tacrolimus BD 0.2 mg/kg per day (Arm 1; n=309), QD 0.2 mg/kg per day (Arm 2; n=302), QD 0.3 mg/kg per day (Arm 3; n=304) all with mycophenolate mofetil and corticosteroids (tapered) over 24 weeks, or tacrolimus QD 0.2 mg/kg per day with mycophenolate mofetil, basiliximab, and corticosteroids given only perioperatively (Arm 4; n=283). The primary composite endpoint (efficacy failure; per protocol set) was defined as graft loss, biopsy-confirmed acute rejection, or graft dysfunction at week 24. Graft dysfunction was defined as estimated glomerular filtration rate Modification of Diet in Renal Disease-4 formula of less than 40 mL/min/1.73 m(2). The prespecified noninferiority margin was 12.5%. RESULTS: The per protocol set included 976 patients: 237, 263, 246, and 230 patients in Arms 1 to 4, respectively. Noninferiority of the composite endpoint was demonstrated for Arm 2 versus Arm 1; Kaplan–Meier estimates of efficacy failure were 42.2% and 40.6%, respectively (difference, −1.6%; 95% confidence interval [CI], −12.2% to 9.0%). Noninferiority to Arm 1 was not confirmed for Arm 3 (difference, −3.5%; 95% CI, −13.6% to 6.6%) or Arm 4 (difference, −7.1%; 95% CI, −16.1% to 1.9%). Graft dysfunction (estimated glomerular filtration rate <40 mL/min/1.73 m(2)) was the main determinant of composite-endpoint efficacy failure across all arms. CONCLUSIONS: In patients representative of the European kidney transplant population, tacrolimus QD-based immunosuppression (0.2 mg/kg/day), without induction, showed similar efficacy to 0.2 mg/kg per day tacrolimus BD. Lippincott Williams & Wilkins 2013-11-27 2013-11-19 /pmc/articles/PMC3864174/ /pubmed/23982340 http://dx.doi.org/10.1097/TP.0b013e3182a203bd Text en Copyright © 2013 by Lippincott Williams & Wilkins http://creativecommons.org/licenses/by-nc-nd/3.0 This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivitives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.
spellingShingle Clinical and Translational Research
Albano, Laetitia
Banas, Bernhard
Klempnauer, Juergen L.
Glyda, Maciej
Viklicky, Ondrej
Kamar, Nassim
OSAKA Trial: A Randomized, Controlled Trial Comparing Tacrolimus QD and BD in Kidney Transplantation
title OSAKA Trial: A Randomized, Controlled Trial Comparing Tacrolimus QD and BD in Kidney Transplantation
title_full OSAKA Trial: A Randomized, Controlled Trial Comparing Tacrolimus QD and BD in Kidney Transplantation
title_fullStr OSAKA Trial: A Randomized, Controlled Trial Comparing Tacrolimus QD and BD in Kidney Transplantation
title_full_unstemmed OSAKA Trial: A Randomized, Controlled Trial Comparing Tacrolimus QD and BD in Kidney Transplantation
title_short OSAKA Trial: A Randomized, Controlled Trial Comparing Tacrolimus QD and BD in Kidney Transplantation
title_sort osaka trial: a randomized, controlled trial comparing tacrolimus qd and bd in kidney transplantation
topic Clinical and Translational Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3864174/
https://www.ncbi.nlm.nih.gov/pubmed/23982340
http://dx.doi.org/10.1097/TP.0b013e3182a203bd
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