Results from this study were presented in part at the International Congress of the Transplant Society in Sydney, Australia, August 10–14, 2008.
Sirolimus Conversion Regimen Versus Continued Calcineurin Inhibitors in Liver Allograft Recipients: A Randomized Trial
Version of Record online: 10 JAN 2012
© copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons
American Journal of Transplantation
Volume 12, Issue 3, pages 694–705, March 2012
How to Cite
Abdelmalek, M. F., Humar, A., Stickel, F., Andreone, P., Pascher, A., Barroso, E., Neff, G. W., Ranjan, D., Toselli, L. T., Gane, E. J., Scarola, J., Goldberg-Alberts, R., Maller, E. S., Lo, C.-M. and for the Sirolimus Liver Conversion Trial Study Group (2012), Sirolimus Conversion Regimen Versus Continued Calcineurin Inhibitors in Liver Allograft Recipients: A Randomized Trial. American Journal of Transplantation, 12: 694–705. doi: 10.1111/j.1600-6143.2011.03919.x
- Issue online: 28 FEB 2012
- Version of Record online: 10 JAN 2012
- Received 04 February 2011, revised 23 August 2011 and accepted for publication 30 August 2011
- Calcineurin inhibitor;
- liver transplantation;
- maintenance therapy;
A large prospective, open-label, randomized trial evaluated conversion from calcineurin inhibitor (CNI)- to sirolimus (SRL)-based immunosuppression for preservation of renal function in liver transplantation patients. Eligible patients received liver allografts 6–144 months previously and maintenance immunosuppression with CNI (cyclosporine or tacrolimus) since early posttransplantation. In total, 607 patients were randomized (2:1) to abrupt conversion (<24 h) from CNI to SRL (n = 393) or CNI continuation for up to 6 years (n = 214). Between-group changes in baseline-adjusted mean Cockcroft–Gault GFR at month 12 (primary efficacy end point) were not significant. The primary safety end point, noninferiority of cumulative rate of graft loss or death at 12 months, was not met (6.6% vs. 5.6% in the SRL and CNI groups, respectively). Rates of death at 12 months were not significantly different, and no true graft losses (e.g. liver transplantation) were observed during the 12-month period. At 52 weeks, SRL conversion was associated with higher rates of biopsy-confirmed acute rejection (p = 0.02) and discontinuations (p < 0.001), primarily for adverse events. Adverse events were consistent with known safety profiles. In conclusion, liver transplantation patients showed no demonstrable benefit 1 year after conversion from CNI- to SRL-based immunosuppression.