3. Design of the OPTIMIZE study: 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

S.E. de Boer, J.S.F. Sanders, F.J. Bemelman, A.W. Gomes Neto, L.B. Hilbrands, D. Kuypers, S. P. Berger, S.A. Nurmohamed, H. Bouwsma, A.P.J. de Vries, A.D. van Zuilen, D.A. Hesselink

Wednesday 4 march 2020

0:00 - 0:00h at Toon Hermans Foyer

Parallel session: Postersessie 1 – Klinische abstracts

Background: In 2015, more than 30% of the 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 observed amongst them. Elderly do have increased rates of malignancies and infection-related mortality. Poor renal function in elderly patients may be related to both pre-existing kidney damage (due to older donor age) and to increased susceptibility to toxicity of calcineurin inhibitors (CNI’s). Hence, it is essential to shift the focus from prevention of rejection to preservation of graft function and prevention of over-immunosuppression in the elderly. The OPTIMIZE study tests the hypothesis that reduced CNI exposure in combination with everolimus will lead to better kidney function, a reduced incidence of complications and improved quality of life for kidney transplant recipients aged 65 years and older, compared to the standard immunosuppressive regimen.

Methods: This open label, randomized, multicenter, clinical trial will include 374 elderly patients (≥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 the standard, tacrolimus-based immunosuppressive regimen (arm 1) or an adapted immunosuppressive regimen with reduced CNI exposure in combination with everolimus (arm 2). 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. Secondary endpoints include rejection, immunosenescence, frailty, co-morbidities and quality of life and will be analyzed in both the complete study population and the separate strata. Also, a cost-effectiveness analysis will be done.

Results: Thus far, 11 participants are enrolled in the first center. Four other centers will start at the end of 2019, and the last two will start in the beginning of 2020.

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 knowledge about immunosenescence and outcome after kidney transplantation in elderly recipients.