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Rationale and design of the OPTIMIZE trial: OPen label multicenter randomized trial comparing standard IMmunosuppression with tacrolimus and mycophenolate mofetil with a low exposure tacrolimus regimen In combination with everolimus in de novo renal transplantation in Elderly patients

BACKGROUND: In 2019, more than 30 % of all newly transplanted kidney transplant recipients in The Netherlands were above 65 years of age. Elderly patients are less prone to rejection, and death censored graft loss is less frequent compared to younger recipients. Elderly recipients do have increased...

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Autores principales: de Boer, S. E., Sanders, J. S.F., Bemelman, F. J., Betjes, M. G.H., Burgerhof, J. G.M., Hilbrands, L., Kuypers, D., van Munster, B. C., Nurmohamed, S. A., de Vries, A. P.J., van Zuilen, A. D., Hesselink, D. A., Berger, S. P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172178/
https://www.ncbi.nlm.nih.gov/pubmed/34078323
http://dx.doi.org/10.1186/s12882-021-02409-8
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author de Boer, S. E.
Sanders, J. S.F.
Bemelman, F. J.
Betjes, M. G.H.
Burgerhof, J. G.M.
Hilbrands, L.
Kuypers, D.
van Munster, B. C.
Nurmohamed, S. A.
de Vries, A. P.J.
van Zuilen, A. D.
Hesselink, D. A.
Berger, S. P.
author_facet de Boer, S. E.
Sanders, J. S.F.
Bemelman, F. J.
Betjes, M. G.H.
Burgerhof, J. G.M.
Hilbrands, L.
Kuypers, D.
van Munster, B. C.
Nurmohamed, S. A.
de Vries, A. P.J.
van Zuilen, A. D.
Hesselink, D. A.
Berger, S. P.
author_sort de Boer, S. E.
collection PubMed
description BACKGROUND: In 2019, more than 30 % of all newly transplanted kidney transplant recipients in The Netherlands were above 65 years of age. Elderly patients are less prone to rejection, and death censored graft loss is less frequent compared to younger recipients. Elderly recipients do have increased rates of malignancy and infection-related mortality. Poor kidney transplant function in elderly recipients may be related to both pre-existing (i.e. donor-derived) kidney damage and increased susceptibility to nephrotoxicity of calcineurin inhibitors (CNIs) in kidneys from older donors. Hence, it is pivotal to shift the focus from prevention of rejection to preservation of graft function and prevention of over-immunosuppression in the elderly. The OPTIMIZE study will test the hypothesis that reduced CNI exposure in combination with everolimus will lead to better kidney transplant function, a reduced incidence of complications and improved health-related quality of life for kidney transplant recipients aged 65 years and older, compared to standard immunosuppression. METHODS: This open label, randomized, multicenter clinical trial will include 374 elderly kidney transplant recipients (≥ 65 years) and consists of two strata. Stratum A includes elderly recipients of a kidney from an elderly deceased donor and stratum B includes elderly recipients of a kidney from a living donor or from a deceased donor < 65 years. In each stratum, subjects will be randomized to a standard, tacrolimus-based immunosuppressive regimen with mycophenolate mofetil and glucocorticoids or an adapted immunosuppressive regimen with reduced CNI exposure in combination with everolimus and glucocorticoids. The primary endpoint is ‘successful transplantation’, defined as survival with a functioning graft and an eGFR ≥ 30 ml/min per 1.73 m(2) in stratum A and ≥ 45 ml/min per 1.73 m(2) in stratum B, after 2 years, respectively. CONCLUSIONS: The OPTIMIZE study will help to determine the optimal immunosuppressive regimen after kidney transplantation for elderly patients and the cost-effectiveness of this regimen. It will also provide deeper insight into immunosenescence and both subjective and objective outcomes after kidney transplantation in elderly recipients. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03797196, registered January 9th, 2019. EudraCT: 2018-003194-10, registered March 19th, 2019. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12882-021-02409-8.
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spelling pubmed-81721782021-06-03 Rationale and design of the OPTIMIZE trial: OPen label multicenter randomized trial comparing standard IMmunosuppression with tacrolimus and mycophenolate mofetil with a low exposure tacrolimus regimen In combination with everolimus in de novo renal transplantation in Elderly patients de Boer, S. E. Sanders, J. S.F. Bemelman, F. J. Betjes, M. G.H. Burgerhof, J. G.M. Hilbrands, L. Kuypers, D. van Munster, B. C. Nurmohamed, S. A. de Vries, A. P.J. van Zuilen, A. D. Hesselink, D. A. Berger, S. P. BMC Nephrol Study Protocol BACKGROUND: In 2019, more than 30 % of all newly transplanted kidney transplant recipients in The Netherlands were above 65 years of age. Elderly patients are less prone to rejection, and death censored graft loss is less frequent compared to younger recipients. Elderly recipients do have increased rates of malignancy and infection-related mortality. Poor kidney transplant function in elderly recipients may be related to both pre-existing (i.e. donor-derived) kidney damage and increased susceptibility to nephrotoxicity of calcineurin inhibitors (CNIs) in kidneys from older donors. Hence, it is pivotal to shift the focus from prevention of rejection to preservation of graft function and prevention of over-immunosuppression in the elderly. The OPTIMIZE study will test the hypothesis that reduced CNI exposure in combination with everolimus will lead to better kidney transplant function, a reduced incidence of complications and improved health-related quality of life for kidney transplant recipients aged 65 years and older, compared to standard immunosuppression. METHODS: This open label, randomized, multicenter clinical trial will include 374 elderly kidney transplant recipients (≥ 65 years) and consists of two strata. Stratum A includes elderly recipients of a kidney from an elderly deceased donor and stratum B includes elderly recipients of a kidney from a living donor or from a deceased donor < 65 years. In each stratum, subjects will be randomized to a standard, tacrolimus-based immunosuppressive regimen with mycophenolate mofetil and glucocorticoids or an adapted immunosuppressive regimen with reduced CNI exposure in combination with everolimus and glucocorticoids. The primary endpoint is ‘successful transplantation’, defined as survival with a functioning graft and an eGFR ≥ 30 ml/min per 1.73 m(2) in stratum A and ≥ 45 ml/min per 1.73 m(2) in stratum B, after 2 years, respectively. CONCLUSIONS: The OPTIMIZE study will help to determine the optimal immunosuppressive regimen after kidney transplantation for elderly patients and the cost-effectiveness of this regimen. It will also provide deeper insight into immunosenescence and both subjective and objective outcomes after kidney transplantation in elderly recipients. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03797196, registered January 9th, 2019. EudraCT: 2018-003194-10, registered March 19th, 2019. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12882-021-02409-8. BioMed Central 2021-06-02 /pmc/articles/PMC8172178/ /pubmed/34078323 http://dx.doi.org/10.1186/s12882-021-02409-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Study Protocol
de Boer, S. E.
Sanders, J. S.F.
Bemelman, F. J.
Betjes, M. G.H.
Burgerhof, J. G.M.
Hilbrands, L.
Kuypers, D.
van Munster, B. C.
Nurmohamed, S. A.
de Vries, A. P.J.
van Zuilen, A. D.
Hesselink, D. A.
Berger, S. P.
Rationale and design of the OPTIMIZE trial: OPen label multicenter randomized trial comparing standard IMmunosuppression with tacrolimus and mycophenolate mofetil with a low exposure tacrolimus regimen In combination with everolimus in de novo renal transplantation in Elderly patients
title Rationale and design of the OPTIMIZE trial: OPen label multicenter randomized trial comparing standard IMmunosuppression with tacrolimus and mycophenolate mofetil with a low exposure tacrolimus regimen In combination with everolimus in de novo renal transplantation in Elderly patients
title_full Rationale and design of the OPTIMIZE trial: OPen label multicenter randomized trial comparing standard IMmunosuppression with tacrolimus and mycophenolate mofetil with a low exposure tacrolimus regimen In combination with everolimus in de novo renal transplantation in Elderly patients
title_fullStr Rationale and design of the OPTIMIZE trial: OPen label multicenter randomized trial comparing standard IMmunosuppression with tacrolimus and mycophenolate mofetil with a low exposure tacrolimus regimen In combination with everolimus in de novo renal transplantation in Elderly patients
title_full_unstemmed Rationale and design of the OPTIMIZE trial: OPen label multicenter randomized trial comparing standard IMmunosuppression with tacrolimus and mycophenolate mofetil with a low exposure tacrolimus regimen In combination with everolimus in de novo renal transplantation in Elderly patients
title_short Rationale and design of the OPTIMIZE trial: OPen label multicenter randomized trial comparing standard IMmunosuppression with tacrolimus and mycophenolate mofetil with a low exposure tacrolimus regimen In combination with everolimus in de novo renal transplantation in Elderly patients
title_sort rationale and design of the optimize trial: open label multicenter randomized trial comparing standard immunosuppression with tacrolimus and mycophenolate mofetil with a low exposure tacrolimus regimen in combination with everolimus in de novo renal transplantation in elderly patients
topic Study Protocol
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172178/
https://www.ncbi.nlm.nih.gov/pubmed/34078323
http://dx.doi.org/10.1186/s12882-021-02409-8
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