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. 2021 Jun 2;22(1):208.
doi: 10.1186/s12882-021-02409-8.

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

S E de Boer  1 , J S F Sanders  2 , F J Bemelman  3 , M G H Betjes  4 , J G M Burgerhof  5 , L Hilbrands  6 , D Kuypers  7 , B C van Munster  8 , S A Nurmohamed  3 , A P J de Vries  9 , A D van Zuilen  10 , D A Hesselink  4 , S P Berger  2
Affiliations

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

S E de Boer et al. BMC Nephrol. .

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.

Keywords: (Health-related) quality of life; Elderly kidney transplant recipients; Everolimus; Frailty; Immunosenescence; Multicenter trial; Patient-reported outcomes; Randomized clinical trial; Reduced CNI exposure; mTOR inhibitor.

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Conflict of interest statement

LBH has received consulting fees from Chiesi and grant support from Chiesi and Sandoz (paid to Radboudumc).

APJdV has received consulting fees from Chiesi and Sandoz and grant support from Chiesi and Sandoz (paid to LUMC).

DAH has received lecture and consulting fees from Astellas Pharma and Chiesi Pharma, as well as grant support from Astellas Pharma and Chiesi Pharma (paid to Erasmus MC).

SPB has received lecture and consulting fees from Novartis (paid to UMCG) and grant support from Novartis and Chiesi.

Figures

Fig. 1
Fig. 1
OPTIMIZE study design. TMP = tacrolimus, mycophenolate mofetil, prednisolon, TAC = tacrolimus, CsA = cyclosporine A, BAX = basiliximab, RND = randomization, TEP = tacrolimus, everolimus, prednisolone, EVR = everolimus
See this image and copyright information in PMC

References

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