Efficacy and Safety of Early Cyclosporine Conversion to Sirolimus with Continued MMF—Four-Year Results of the Postconcept Study.
Lebranchu Y, Thierry A, et al.American Journal of Transplantation, 11(8): 1665-1675, 2011.
Aims
To evaluate the long term efficacy and safety of conversion from cyclosporine (CsA) to sirolimus in kidney transplant recipients.
Interventions
Continue CsA versus convert from CsA to sirolimus at 3 months post-transplantation. All patients received steroids and mycophenolate mofetil (MMF).
Participants
162 recipients who received a first cadaver donor kidney transplant.
Outcomes
The primary efficacy endpoint was renal function measured as the estimated glomerular filtration rate at 4 years post-transplantation; other outcomes included patient and graft survival and occurrence of acute rejection. Safety endpoints included the occurrence of cancer, new-onset diabetes after transplantation (NODAT), nephropathy and all serious adverse effects. Other clinical and laboratory parameters included systolic and diastolic blood pressure, haemoglobin, proteinuria and lipid profile (total cholesterol, low-density lipoprotein, high density lipoprotein, triglycerides).
Follow-up
4 years post-transplantation
CET Conclusions
In this long term follow-up of the Concept trial where patients had been converted to sirolimus at 3 months after transplantation and were compared with patients in the cyclosporine group, both groups continued to receive MMF and steroids. At 4 years there was a modest improvement in renal function in the patients converted to sirolimus. In low risk recipients of a first cadaver renal transplant conversion to sirolimus appeared to continue to maintain better renal function in the sirolimus group in combination with MMF and steroids. However there was a greater incidence of proteinuria and NODAT in the patients converted to sirolimus. A weakness of the study pointed out by the authors was the fact that investigators were allowed to modify the immunosuppressive agents used and more patients had withdrawn from their original immunosuppression in the sirolimus group, but this did mainly occur in the first year after transplantation.
Data analysis
Per protocol analysis
Quality notes
This is a sub-analysis of a previous publication of the same RCT: Lebranchu Y, Thierry A, Toupance O, et al. Efficacy on renal function of early conversion from cyclosporine to sirolimus 3 months after renal transplantation: Concept study. Am J Transplant 2009; 9: 1115–1123. The methodological quality assessment was based on the previous publication.
Trial registration
2004-002987-62 (Eudract)