The efficacy and safety of cyclosporine reduction in de novo renal allograft patients receiving sirolimus and corticosteroids: results from an open-label comparative study.
Muhlbacher F, Neumayer HH, et al.Transplant International 2014;27(2):176-86
Aims
To investigate whether reduced dose cyclosporine (rCsA) combined with sirolimus and corticosteroids minimizes acute rejection, as well as the nephrotoxicity associated with standard cyclosporine dosing.
Interventions
Patients were randomised to receive rCsA or to continue standard dose CsA.
Participants
420 de novo renal allograft recipients.
Outcomes
Primary outcomes included the incidence of biopsy-confirmed acute rejection (BCAR) and renal function at 12 months. Secondary outcomes included the incidence of BCAR at 6 and 9 months after transplantation, patient and graft survival at 6 and 12 months and renal allograft function. Additional secondary outcomes included incidence of presumed acute allograft rejection and repeated episodes of acute rejection, the time to first BCAR and the severity of rejection. Infection, histological confirmed lymphoproliferative disease or malignancy, and premature withdrawal from study medication were also
Follow-up
12 months
CET Conclusions
There was no difference in biopsy proven acute rejection rates between the standard CSA and reduced dose CSA groups. The reduced dose CSA group had lower serum creatinine at 12 months after transplantation. Graft and patient survival rates were similar. Of concern is the very large proportion of patients (approximately 30%) that dropped out after enrolment, both before and after randomisation. The vast majority of these dropouts were due to adverse events, which were evenly spread between the two arms. The patient population is selected by the exclusion of patients with adverse events during the first four weeks, resulting in better overall outcomes. The description of the sample size calculation is impenetrable and the study has taken over ten years to be published due to an unelaborated “variety of reasonsâ€.
Data analysis
Strict intention-to-treat analysis
Trial registration
ClinicalTrials.gov - NCT00507793