TY - JOUR
T1 - Sirolimus conversion regimen versus continued calcineurin inhibitors in liver allograft recipients: a randomized trial
AU - Adbelmalek, MF
AU - Humar, A
AU - Stickel, F
AU - Andreone, P
AU - Pascher, A
AU - Barroso, E
AU - Neff, GW
AU - Ranjan, D
AU - Toselli, LT
AU - Gane, E
AU - Scarola, J
AU - Goldberg-Alberts, R
AU - Maller, E S
AU - Lo, CM
AU - Padbury, Robert
PY - 2012/3
Y1 - 2012/3
N2 - 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. Conversion from calcineurin inhibitor to sirolimus-based immunosuppression for preservation of renal function in liver transplant recipients shows no demonstrable benefit at one year. See editorial by McKenna and Trotter on page 521.
AB - 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. Conversion from calcineurin inhibitor to sirolimus-based immunosuppression for preservation of renal function in liver transplant recipients shows no demonstrable benefit at one year. See editorial by McKenna and Trotter on page 521.
KW - Calcineurin inhibitor
KW - liver transplantation
KW - maintenance therapy
KW - nephrotoxicity
KW - sirolimus
UR - http://www.scopus.com/inward/record.url?scp=84857648997&partnerID=8YFLogxK
U2 - 10.1111/j.1600-6143.2011.03919.x
DO - 10.1111/j.1600-6143.2011.03919.x
M3 - Article
SN - 1600-6135
VL - 12
SP - 694
EP - 705
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 3
ER -