Transplant Trial Watch

Everolimus in de novo kidney transplant recipients participating in the Eurotransplant senior program: Results of a prospective randomized multicenter study (SENATOR).

Brakemeier, S., Arns, W. et al. (2019).

PLoS ONE [Electronic Resource]14(9): e0222730.


Aims
This study aims to evalute the efficacy, safety and tolerability of a steroid- and CNI-free regimen with everolimus and mycophenolic acid (MPA) under the umbrella of induction with the interleukin-2 receptor (IL-2R) antibody basiliximab compared with a standard cyclosporine (CsA)-based immunosuppressive regimen in de novo renal transplant recipients participating in the Eurotransplant senior program (SENATOR).

Interventions
Patients were randomized to either the Control or Everolimus group. The control group continued the prior CNI-based regimen with MPA + CsA as administered prior to randomization. The Everolimus group switch to a steroid and CNI-free regimen with MPA + everolimus.

Participants
207 Patients aged >65 years receiving their first kidney from a deceased donor aged >65 years in the Eurotransplant Senior Program (ESP), undergoing steroid withdrawal at week 2 post-transplant.

Outcomes
The primary outcome measured was renal function at month 6 after kidney transplant, as assessed by estimated glomerular filtration rate (eGFR). Secondary outcomes comprised renal function (eGFR and serum creatinine levels), safety and tolerability (evaluated by adverse events and serious adverse events), efficacy (as measured by graft loss and graft death) and treatment failure at 6 months.

Follow-up
6 months

CET Conclusions
This was a multicentre randomised controlled trial conducted in 10 transplant centres in Germany. The study was not blinded due to the complexity of the drug regimens used. The study was stopped early due to slow enrolment; almost 63% of those entering the study discontinued prior to randomisation due to many reasons, but most commonly abnormal blood results and adverse events. Of the 53 that were randomised to everolimus, 27 discontinued the drug due to adverse events (15) or unsatisfactory therapeutic effect (10), abnormal lab values (2). Only 1 patient in the control arm had unsatisfactory therapeutic effect and none stopped the control regimen due to adverse events. In the small number that made it into the 6 months analysis there was no significant difference in eGFR. The patient population is described as being somewhat unstable regardless of treatment, and difficult to randomise. Could it have been conducted in a more pragmatic way? The fundamental result is that a very large proportion of those randomised to everolimus did not tolerate it.

Jadad score
3

Data analysis
Strict intention-to-treat analysis

Allocation concealment
Yes

Trial registration
ClinicalTrial.gov- NCT00956293

Funding source
Industry funded