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, vol. 22, pp. 208
Abstract
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 donororfrom 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 m2in stratum A and ≥ 45 ml/min per 1.73 m2in 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.
Authors 13
-
Silke E. de Boer corresponding
University Medical Center Groningen · University of Groningen
Affiliation as printed
Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. s.e.de.boer@umcg.nl
Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
-
University Medical Center Groningen · University of Groningen
Affiliation as printed
Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
-
Amsterdam University Medical Centers
Affiliation as printed
Department of Internal Medicine, Division of Nephrology, Amsterdam Universal Medical Center, Amsterdam, The Netherlands
-
Affiliation as printed
Department of Internal Medicine, Division of Nephrology & Transplantation, Erasmus MC, Erasmus University Medical Center, Rotterdam, The Netherlands
-
University Medical Center Groningen · University of Groningen
Affiliation as printed
Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
-
Radboud University Nijmegen · Radboud University Medical Center
Affiliation as printed
Department of Internal Medicine, Division of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands
-
Universitair Ziekenhuis Leuven
Affiliation as printed
Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium
-
University Medical Center Groningen · University of Groningen
Affiliation as printed
Department of Internal Medicine, Divison of Geriatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
-
Amsterdam University Medical Centers
Affiliation as printed
Department of Internal Medicine, Division of Nephrology, Amsterdam Universal Medical Center, Amsterdam, The Netherlands
-
Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Internal Medicine, Division of Nephrology; and Leiden Transplant Center, Leiden University Medical Center, Leiden University, Leiden, The Netherlands
Department of Internal Medicine, Division of Nephrology
Leiden Transplant Center, Leiden University Medical Center, Leiden University, Leiden, The Netherlands
-
Utrecht University · University Medical Center Utrecht
Affiliation as printed
Department of Internal Medicine, Division of Nephrology, University Medical Center Utrecht, Utrecht, The Netherlands
-
Affiliation as printed
Department of Internal Medicine, Division of Nephrology & Transplantation, Erasmus MC, Erasmus University Medical Center, Rotterdam, The Netherlands
-
University Medical Center Groningen · University of Groningen
Affiliation as printed
Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Cited by 16 stored of 16
16 results
No patents citing this paper on Lens.org (checked 2026-10-11).