title: An open, randomized, multicenter clinical trial of oral tacrolimus in liver allograft transplantation: a comparison of dual vs. triple drug therapy.
abstract: Triple therapy combining an anticalcineurin agent, corticosteroids, and azathioprine (AZA) in liver transplantation has been frequently applied, particularly in Europe. Debates have arisen concerning the use of a third drug (AZA), mainly in patients receiving tacrolimus (TAC). An open-label, multicenter, prospective, and randomized trial was performed to assess the efficacy and safety of TAC and corticosteroids (dual therapy [D]) vs. TAC, corticosteroids, and AZA (triple therapy [T]) in liver transplantation. A total of 180 patients were randomized, 92 in D and 88 in T group. Patients were followed during 3 months for efficacy and safety and up to 24 months for patient and graft survival assessments. The rate of biopsy-proven acute rejection was higher in D than in T group (40.7% vs. 24.4%; P = 0.021). A higher incidence of positive HCV status in D group (55.6% vs. 40.7%; P = 0.049) may explain this difference, since significantly more patients of this HCV subpopulation experienced acute rejection when treated with D therapy (48% vs. 20%; P = 0.008). No treatment differences were apparent for HCV-negative patients. The 24-month graft survival tended to be inferior in T group, 69.8% vs. 75.8% (P = 0.283). Similar results were observed regarding patient survival at the same time point, with values of 72.9% vs. 76.9% (P = 0.573), favoring D group. Both regimens showed comparable safety profiles with the exception of hematological abnormalities, which were more frequently observed in T group. In conclusion, both regimens were shown to be effective although increased toxicity and a trend towards a lower graft and patient survival were observed in T group.
authors.affiliation: Liver Transplantation Unit, Gastroenterology Department, Hospital Ramón y Cajal, Madrid, Spain. mgarciago.hrc@salud.madrid.org
authors.forename: Miguel García
authors.initials: MG
authors.lastname: González
authors.forename: Carlos Pera
authors.initials: CP
authors.lastname: Madrazo
authors.forename: Angel Bernardos
authors.initials: AB
authors.lastname: Rodríguez
authors.forename: Manuel Gómez
authors.initials: MG
authors.lastname: Gutiérrez
authors.forename: J Ignacio
authors.initials: JI
authors.lastname: Herrero
authors.forename: José Mir
authors.initials: JM
authors.lastname: Pallardó
authors.forename: Jorge
authors.initials: J
authors.lastname: Ortiz de Urbina
authors.forename: Pascual Parrilla
authors.initials: PP
authors.lastname: Paricio
mesh_terms: D000284:Administration, Oral; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000368:Aged; D001379:Azathioprine / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy* / Q000401:mortality; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000008:administration & dosage*; D013997:Time Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D001379:Azathioprine; D016559:Tacrolimus