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.

Published on Jun 2, 2021in BMC Nephrology1.913
· DOI :10.1186/S12882-021-02409-8
S E de Boer (UMCG: University Medical Center Groningen), Jan Stephan Sanders22
Estimated H-index: 22
(UMCG: University Medical Center Groningen)
+ 10 AuthorsStefan P. Berger33
Estimated H-index: 33
(UMCG: University Medical Center Groningen)
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.
#1Stefan P. BergerH-Index: 33
#2Claudia Sommerer (University Hospital Heidelberg)H-Index: 35
Last. Julio PascualH-Index: 70
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: TRANSFORM (TRANSplant eFficacy and safety Outcomes with an eveRolimus-based regiMen) was a 24-month, prospective, open-label trial in 2037 de novo renal transplant recipients randomized (1:1) within 24 hours of transplantation to receive everolimus (EVR) with reduced-exposure calcineurin inhibitor (EVR + rCNI) or mycophenolate with standard-exposure CNI. Consistent with previously reported 12-month findings, noninferiority of the EVR + rCNI regimen for the primary endpoint of treated biopsy-pr...
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Last. Flavio Vincenti (UCSF: University of California, San Francisco)H-Index: 83
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Background Everolimus permits reduced calcineurin inhibitor (CNI) exposure, but the efficacy and safety outcomes of this treatment after kidney transplant require confirmation. Methods In a multicenter noninferiority trial, we randomized 2037 de novo kidney transplant recipients to receive, in combination with induction therapy and corticosteroids, everolimus with reduced-exposure CNI (everolimus arm) or mycophenolic acid (MPA) with standard-exposure CNI (MPA arm). The primary end point was trea...
80 CitationsSource
#1Flavia Neri (UNIPD: University of Padua)H-Index: 13
#2Lucrezia Furian (UNIPD: University of Padua)H-Index: 17
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The aging of the on-dialysis population raises the issue of whether to propose elderly patients for kidney transplantation and how to manage their immunosuppression. This study aims to analyze the outcome of kidney transplantation on an Italian series of elderly recipients. We included in this retrospective study all patients over 60 years, receiving a deceased-donor kidney transplantation from January 2004 to December 2014 in two north Italian Centers. We analyzed the correlation of recipient a...
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#1Krishna Karpe (Canberra Hospital)H-Index: 4
#2Girish Talaulikar (Canberra Hospital)H-Index: 13
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30 CitationsSource
#1Y. Qazi (SC: University of Southern California)H-Index: 12
#2David Shaffer (VUMC: Vanderbilt University Medical Center)H-Index: 14
Last. Shamkant MulgaonkarH-Index: 29
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In this 12-month, multicenter, randomized, open-label, noninferiority study, de novo renal transplant recipients (RTxRs) were randomized (1:1) to receive everolimus plus low-dose tacrolimus (EVR+LTac) or mycophenolate mofetil plus standard-dose Tac (MMF+STac) with induction therapy (basiliximab or rabbit anti-thymocyte globulin). Noninferiority of composite efficacy failure rate (treated biopsy-proven acute rejection [tBPAR]/graft loss/death/loss to follow-up) in EVR+LTac versus MMF+STac was mis...
32 CitationsSource
#2Stefan P. Berger (UMCG: University Medical Center Groningen)H-Index: 33
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An increasing number of elderly patients (≥65 years) receive a donor kidney from elderly donors after brain death (DBD) or after circulatory death (DCD). These organs are allocated within the Eurotransplant Senior Program, but outcomes must be evaluated. From the Dutch Organ Transplantation Registry, we selected 3597 recipients (≥18 years) who received a first DBD or DCD kidney during 2002–2012, and categorized them as young or elderly recipients receiving a graft from either a young or elderly ...
31 CitationsSource
#1Burç Dedeoglu (EUR: Erasmus University Rotterdam)H-Index: 5
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Last. Michiel G. H. Betjes (EUR: Erasmus University Rotterdam)H-Index: 60
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#1Michiel G. H. Betjes (EUR: Erasmus University Rotterdam)H-Index: 60
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