title: Comparison of the safety and efficacy of cyclosporine minimization versus cyclosporine elimination in de novo renal allograft patients receiving sirolimus.
abstract: The safety and efficacy of concentration-controlled use of sirolimus (SRL) and cyclosporine (CsA) followed by CsA minimization (CsAm) or elimination (CsAe) beginning at week 13 was compared in a phase 4, open-label, randomized (1:1) trial of renal transplant recipients enrolled between March 2004 and November 2005. The primary endpoint was renal function, measured at 12 months using the Nankivell formula, in patients remaining on therapy. Though a total enrollment of 140 patients in each group was planned to provide an 80% power to detect a difference in means, only 207 subjects were enrolled in this study. Demographic characteristics were similar between groups, with 98.1% recipients of first grafts, 69.1% from living donors, and 7.2% diabetics. At 12 months, there were no differences in renal function (61.08 vs 65.24 mL/min, P = .132); incidence of biopsy-confirmed acute rejection (14.3% vs 22.5%, P = .152); and patient (89.5% vs 92.2%, P = .632), graft (87.6% vs 88.2%, P = .999), and death-censored graft (98.1% vs 94.1%, P = .166) survivals between CsAm and CsAe groups, respectively. There were no differences in the overall rate of study-drug discontinuation (32.4% vs 36.3%, P = .562) but more patients discontinued because of lack of efficacy/graft loss in the CsAe group (4.8% vs 14.7%, P = .018). This study was underpowered to demonstrate the superiority of one regimen over the other. In summary, SRL immunotherapy combined with CsA minimization or elimination showed comparative safety and efficacy. Both regimens offer potential treatment options for de novo renal allograft recipients.
authors.affiliation: Hospital do Rim e Hipertensão, São Paulo, Brazil. heliotedesco@hrim.com.br
authors.forename: H
authors.initials: H
authors.lastname: Tedesco-Silva
authors.forename: V Duro
authors.initials: VD
authors.lastname: Garcia
authors.forename: F L C
authors.initials: FL
authors.lastname: Contieri
authors.forename: D
authors.initials: D
authors.lastname: De Boni Monteiro de Carvalho
authors.forename: I L
authors.initials: IL
authors.lastname: Noronha
authors.forename: R T
authors.initials: RT
authors.lastname: Gonçalves
authors.forename: F Jota
authors.initials: FJ
authors.lastname: de Paula
authors.forename: M
authors.initials: M
authors.lastname: Abbud-Filho
authors.forename: R C
authors.initials: RC
authors.lastname: Manfro
authors.forename: E
authors.initials: E
authors.lastname: David-Neto
authors.forename: F
authors.initials: F
authors.lastname: Alfieri
authors.forename: E
authors.initials: E
authors.lastname: Ikehara
authors.forename: Q
authors.initials: Q
authors.lastname: Jiang
authors.forename: S S
authors.initials: SS
authors.lastname: Tai
authors.forename: J O
authors.initials: JO
authors.lastname: Medina-Pestana
mesh_terms: D000328:Adult; D002102:Cadaver; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005006:Ethnicity; D005260:Female; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000276:immunology* / Q000401:mortality / Q000502:physiology; D019520:Living Donors; D008297:Male; D018579:Patient Selection; D020123:Sirolimus / Q000627:therapeutic use*; D014019:Tissue Donors; D014184:Transplantation, Homologous; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus