The impact of everolimus in reducing cytomegalovirus events in kidney transplant recipients on steroid-avoidance strategy: 3-year follow-up of a randomized clinical trial

Transpl Int. 2018; 31(12):1345-1356.

Aims
To determine whether everolimus (EVR) reduces cytomegalovirus (CMV) events in patients receiving steroid-free regimens.

Interventions
Patients were randomized (1:1) to receive either everolimus (1.5 mg twice daily starting in the first 24 hours post transplant and adjusted to maintain whole blood trough concentrations of 3–8 ng/ml) or mycophenolate sodium (MPS) (720 mg twice daily starting in the first 24 hours post transplant), both within a steroid-free regimen based on low-exposure tacrolimus.

Participants
115 adults (aged 18–75 years who received a primary allograft from non-human leukocyte antigen (HLA) identical living or deceased kidney transplant) were randomized to receive either EVR (n= 59) or MPS (n=56).

Outcomes
The primary outcome was incidence of CMV events. Secondary outcomes were efficacy and safety including biopsy-proven acute rejection, graft loss, patient survival and renal funtion.

Follow-up
3 years

CET Conclusions
The RCT investigated if everolimus compared with mycophenolate sodium as part of steroid-free regimens could prevent cytomegalovirus (CMV) infection and disease in adult recipients of a primary allograft from non human leukocyte antigen (HLA) identical living or deceased kidney donor. A power calculation showed that a sample size of 112 patients would provide 85% power to detect a clinically meaningful difference in the CMV event rate. No details of the randomisation and the allocation procedure were provided. The study included 115 patients and missing values of patients who died or were lost to follow up were estimated using the last value carried forward technique. More patients on MPS discontinued the allocated regimen compared to the everolimus group (26.8% versus 8.5%), which were all due to safety concerns. Patients in the everolimus group had a significantly lower incidence of CMV events but there were no differences for any of the secondary outcomes over the 3-year follow-up period.

Jadad score
3

Data analysis
Modified intention-to-treat analysis

Allocation concealment
No

Trial registration
ClinicalTrials.gov - NCT02084446

Funding source
Industry funded