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
Abstract 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 in...
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| Format: | Article |
| Language: | English |
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BMC
2021-06-01
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| Series: | BMC Nephrology |
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| Online Access: | https://doi.org/10.1186/s12882-021-02409-8 |
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| author | S. E. de Boer J. S.F. Sanders F. J. Bemelman M. G.H. Betjes J. G.M. Burgerhof L. Hilbrands D. Kuypers B. C. van Munster S. A. Nurmohamed A. P.J. de Vries A. D. van Zuilen D. A. Hesselink S. P. Berger |
| author_facet | S. E. de Boer J. S.F. Sanders F. J. Bemelman M. G.H. Betjes J. G.M. Burgerhof L. Hilbrands D. Kuypers B. C. van Munster S. A. Nurmohamed A. P.J. de Vries A. D. van Zuilen D. A. Hesselink S. P. Berger |
| author_sort | S. E. de Boer |
| collection | DOAJ |
| description | Abstract 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 m2 in stratum A and ≥ 45 ml/min per 1.73 m2 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. |
| first_indexed | 2024-12-14T18:39:09Z |
| format | Article |
| id | doaj.art-01bc2a273ab84de0bc1322baa18d8dce |
| institution | Directory Open Access Journal |
| issn | 1471-2369 |
| language | English |
| last_indexed | 2024-12-14T18:39:09Z |
| publishDate | 2021-06-01 |
| publisher | BMC |
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| series | BMC Nephrology |
| spelling | doaj.art-01bc2a273ab84de0bc1322baa18d8dce2022-12-21T22:51:32ZengBMCBMC Nephrology1471-23692021-06-0122111010.1186/s12882-021-02409-8Rationale 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 patientsS. E. de Boer0J. S.F. Sanders1F. J. Bemelman2M. G.H. Betjes3J. G.M. Burgerhof4L. Hilbrands5D. Kuypers6B. C. van Munster7S. A. Nurmohamed8A. P.J. de Vries9A. D. van Zuilen10D. A. Hesselink11S. P. Berger12Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of GroningenDepartment of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of GroningenDepartment of Internal Medicine, Division of Nephrology, Amsterdam Universal Medical CenterDepartment of Internal Medicine, Division of Nephrology & Transplantation, Erasmus MC, Erasmus University Medical CenterDepartment of Epidemiology, University Medical Center Groningen, University of GroningenDepartment of Internal Medicine, Division of Nephrology, Radboud University Medical CenterDepartment of Nephrology and Renal Transplantation, University Hospitals LeuvenDepartment of Internal Medicine, Divison of Geriatrics, University Medical Center Groningen, University of GroningenDepartment of Internal Medicine, Division of Nephrology, Amsterdam Universal Medical CenterDepartment of Internal Medicine, Division of Nephrology; and Leiden Transplant Center, Leiden University Medical Center, Leiden UniversityDepartment of Internal Medicine, Division of Nephrology, University Medical Center UtrechtDepartment of Internal Medicine, Division of Nephrology & Transplantation, Erasmus MC, Erasmus University Medical CenterDepartment of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of GroningenAbstract 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 m2 in stratum A and ≥ 45 ml/min per 1.73 m2 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.https://doi.org/10.1186/s12882-021-02409-8Elderly kidney transplant recipientsReduced CNI exposuremTOR inhibitorEverolimus(Health-related) quality of lifePatient-reported outcomes |
| spellingShingle | S. E. de Boer J. S.F. Sanders F. J. Bemelman M. G.H. Betjes J. G.M. Burgerhof L. Hilbrands D. Kuypers B. C. van Munster S. A. Nurmohamed A. P.J. de Vries A. D. van Zuilen D. A. Hesselink S. P. Berger 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 BMC Nephrology Elderly kidney transplant recipients Reduced CNI exposure mTOR inhibitor Everolimus (Health-related) quality of life Patient-reported outcomes |
| 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 | Elderly kidney transplant recipients Reduced CNI exposure mTOR inhibitor Everolimus (Health-related) quality of life Patient-reported outcomes |
| url | https://doi.org/10.1186/s12882-021-02409-8 |
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