Efficacy of everolimus with reduced-exposure cyclosporine in de novo kidney transplant patients at increased risk for efficacy events: analysis of a randomized trial.
Carmellini M, Garcia V, et al.Journal of Nephrology 2015; 28(5): 633-639.
Aims
To examine the efficacy of de novo everolimus with reduced-exposure calcineurin inhibitor (CNI) in kidney transplant subpopulations at increased risk for efficacy events.
Interventions
All patients received induction with basiliximab and were randomized to everolimus targeting a trough concentration of 3–8 ng/ml or 6-12ng/ml with reduced-exposure cyclosporine (CsA), or mycophenolic acid with standard-exposure CsA.
Participants
833 de novo primary kidney transplant recipients aged 18-70 years
Outcomes
The primary measured outcomes were biopsy-proven acute rejection (BPAR), graft loss, death and loss to follow-up. Other measured outcomes were CsA trough concentration, estimated glomerular filtration rate and adverse events.
Follow-up
24 months
CET Conclusions
In this study everolimus (at two different doses) was used alongside reduced-dose cyclosporine in comparison with mycophenolate and standard-dose cyclosporine. At first glance it appears that a "high risk" group was identified using the following risk factors: male gender, black race, DGF, HLA mismatch >=3, older age. In fact the total study population was broken down into each of these groups separately and the composite outcome was then examined for each treatment arm; there were no apparent differences in overall numbers or hazard ratio. Each of the "at risk" sub-populations is small, as one might imagine, and this does call into question the validity of the equivalence reported. Perhaps a single "high risk group" with one or more of the risk factors identified would have provided a more robust assessment.
Data analysis
Strict intention-to-treat analysis
Quality notes
Previously assessed as Tedesco Silva H Jr, et al. Everolimus plus reduced-exposure CsA versus mycophenolic acid plus standard-exposure CsA in renal transplant recipients. Am J Transplant 2010:1401–1413
Trial registration
Clinicaltrials.gov - NCT00251004