Prospective randomized study comparing everolimus and mycophenolate sodium in de novo kidney transplant recipients from expanded criteria deceased donor.Ferreira, A. N., Felipe, C. R. et al. (2019).
Transplant International 06: 06.
This study aimed to compare everolimus and mycophenolate sodium in de novo kidney transplant recipients from expanded criteria deceased donors (ECD) to identify an optimal immunosuppressive regimen for ECD kidneys.
Patients were randomized to receive either antithymocyte globulin induction, delayed introduction of reduced dose tacrolimus, prednisone and everolimus (r-ATG/EVR) or mycophenolate (r-ATG/MPS).
171 ECD kidney transplant patients.
The primary end-point was assessed as the incidence of CMV infection at 12 months. Secondary endpoints of this study included treatment failure (first biopsy proven acute rejection (BPAR), graft loss or death) and safety.
This is clearly reported trial that was well conducted with adequate randomization, although blinding was not undertaken. The study was adequately powered taking into account expected event rates and dropouts. The everolimus arm had a drastically reduced risk of CMV infection/disease in the first year (14% versus 72% approximately). However, the balance between preventing infection, and risking allograft rejection, seemed to be tipped too far in this study; The incidence of graft loss, death and rejection were all significantly higher in the everolimus arm, and mean GFR was significantly worse. The study was therefore terminated before reaching the target inclusion numbers. ECD kidneys have a higher risk of graft loss and mortality, in this group it seems that the proposed immune suppression regimen to reduce CMV disease comes at too high a risk to the transplant. There is pressure in the healthcare setting of this trial to avoid CMV prophylaxis, but that looks inadvisable given the results of this study in this particular setting. The authors agree that, under the conditions of this trial, everolimus should be avoided in ECD kidney transplantation.
ClinicalTrials.gov - NCT01895049