title: Sirolimus conversion regimen versus continued calcineurin inhibitors in liver allograft recipients: a randomized trial.
abstract: 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.
authors.affiliation: University of Florida, Gainesville, FL, USA. manal.abdelmalek@duke.edu
authors.forename: M F
authors.initials: MF
authors.lastname: Abdelmalek
authors.forename: A
authors.initials: A
authors.lastname: Humar
authors.forename: F
authors.initials: F
authors.lastname: Stickel
authors.forename: P
authors.initials: P
authors.lastname: Andreone
authors.forename: A
authors.initials: A
authors.lastname: Pascher
authors.forename: E
authors.initials: E
authors.lastname: Barroso
authors.forename: G W
authors.initials: GW
authors.lastname: Neff
authors.forename: D
authors.initials: D
authors.lastname: Ranjan
authors.forename: L T
authors.initials: LT
authors.lastname: Toselli
authors.forename: E J
authors.initials: EJ
authors.lastname: Gane
authors.forename: J
authors.initials: J
authors.lastname: Scarola
authors.forename: R G
authors.initials: RG
authors.lastname: Alberts
authors.forename: E S
authors.initials: ES
authors.lastname: Maller
authors.forename: C-M
authors.initials: CM
authors.lastname: Lo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000008:administration & dosage; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020123:Sirolimus / Q000008:administration & dosage*; D016559:Tacrolimus / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus; D016559:Tacrolimus