Early Conversion From Calcineurin Inhibitor- to Everolimus-Based Therapy Following Kidney Transplantation: Results of the Randomized ELEVATE Trial.de Fijter JW, Holdaas H, et al.
American Journal of Transplantation 2017; 17(7): 1853-1867.
To assess the effect of early conversion from calcineurin inhibitor (CNI) therapy to everolimus in kidney transplant recipients.
Participants were randomized at 10–14 weeks posttransplant to convert from CNI therapy to everolimus, or remain on a standard CNI regimen. All patients received basiliximab induction with tacrolimus or cyclosporine, enteric-coated mycophenolate sodium and steroids.
715 adult recipients of a first or second kidney transplant from a deceased or living donor with a cold ischemia time <24 h.
The primary outcome measured was the change in estimated glomerular filtration rate from randomization to month 12. Secondary measured outcomes were also measured from randomization to month 12 and included the change in left ventricular mass index, and a composite of treated biopsy proven acute rejection, graft loss or death.
This paper reports the results of the ELEVATE trial, a multicentre RCT comparing early (week 10-14) conversion to everolimus with continuation of CNI-based therapy in standard criteria kidney recipients. The primary endpoint, change in MDRD eGFR from randomisation to month 12, did not differ between groups. Incidence of biopsy-proven acute rejection was higher in the CNI arm, which is attributed mainly to the cyclosporine-treated patients. There is also a suggestion of increased incidence of donor-specific antibodies in the everolimus group, but the data are very incomplete making firm conclusions difficult. Around 25% of patients did not tolerate everolimus therapy, in keeping with previous mTOR trials. These results suggest that there is little if any benefit of conversion to everolimus in patients with a relatively well-preserved graft function. It should be noted that only 50-60% of patients were within the everolimus trough target range at any one study visit, much lower than tacrolimus (70-75%) and cyclosporine (60-80%). This may reflect poor compliance due to adverse effects, and possibly explain the inferior protection against BPAR seen in the study.
Clinicaltrials.gov - NCT01114529