A randomized, controlled trial of everolimus based dual immunosuppression vs standard of care in de novo kidney transplant recipients.
Chadban S, Eris J, et al.Transplant International 2014; 27(3): 302-11.
Aims
To assess whether everolimus and reduced dose steroids or everolimus and reduced dose cyclosporine (CsA) provide non-inferior safety and efficacy compared with CsA, mycophenolic acid (MPA) and steroids.
Interventions
All patients received cyclosporine microemulsion, mycophenolate sodium and corticosteroids for 14 days. Patients were randomised to receive (1) everolimus and CSA/ MPA withdrawal or (2) everolimus, reduced CSA and MPA/corticosteroid withdrawal. The control group (3) received CsA, MPA and steroids for the duration of the trial. From day 60-120 the CNI withdrawal group received an increased everolimus dose, steroids were continued and CsA was discontinued. The steroid withdrawal group continued on everolimus, CsA was decreased to a dose of 50% and prednisone was gradually withdrawn.
Participants
126 de novo renal transplant recipients
Outcomes
The primary outcome of this study was the difference in kidney function at 12 months after kidney transplantation. The secondary outcomes included the incidence of biopsy proven acute rejection, graft survival, death and loss to follow up.
Follow-up
36 months
CET Conclusions
This multicentre international trial (SOCRATES) extended over 4 years but only 126 patients were recruited in that time and there is no question that the study is underpowered. All the recipients are low risk recipients and the majority of donors comprised living donors, both living related and living unrelated. CSA was reduced and eventually withdrawn together with mycophenolate in one arm while in the other steroids were also withdrawn. There were three arms to this trial but the MPA/steroid withdrawal arm was discontinued due to a high incidence of acute rejection. In terms of the primary outcome there was no difference in renal function at 12 months nor was there any difference in adverse events. However it should be noted that the incidence of diarrhoea was quite high in all three arms despite the use of myfortic. Thus at 12 months there appear to be no benefit in switching to everolimus. The investigators propose to evaluate renal function again at 3 years.
Data analysis
Modified intention-to-treat analysis
Trial registration
ClinicalTrials.gov - NCT00371826