An open, randomized, multicenter clinical trial of oral tacrolimus in liver allograft transplantation: a comparison of dual vs. triple drug therapy.
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.
González
Miguel García
MG
Liver Transplantation Unit, Gastroenterology Department, Hospital Ramón y Cajal, Madrid, Spain. mgarciago.hrc@salud.madrid.org
Madrazo
Carlos Pera
CP
Rodríguez
Angel Bernardos
AB
Gutiérrez
Manuel Gómez
MG
Herrero
J Ignacio
JI
Pallardó
José Mir
JM
Ortiz de Urbina
Jorge
J
Paricio
Pascual Parrilla
PP
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
D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D001379:Azathioprine; D016559:Tacrolimus