title: Reduced-dose tacrolimus with mycophenolate mofetil vs. standard-dose tacrolimus in liver transplantation: a randomized study.
abstract: We conducted a multicenter randomized study in liver transplantation to compare standard-dose tacrolimus to reduced-dose tacrolimus with mycophenolate mofetil to reduce the occurrence of tacrolimus side effects. Two primary outcomes (censored criteria) were monitored during 48 weeks post-transplantation: occurrence of renal dysfunction or arterial hypertension or diabetes (evaluating benefit) and occurrence of acute graft rejection (evaluating risk). Interim analyses were performed every 40 patients to stop the study in the case of increased risk of graft rejection. One hundred and ninety-five patients (control: 100; experimental: 95) had been included when the study was stopped. Acute graft rejection occurred in 46 (46%) and 28 (30%) patients in control and experimental groups, respectively (HR = 0.59; 95% CI: [0.37-0.94]; p = 0.024). Renal dysfunction or arterial hypertension or diabetes occurred in 80 (80%) and 61 (64%) patients in control and experimental groups, respectively (HR = 0.68; 95% CI: [0.49-0.95]; p = 0.021). Renal dysfunction occurred in 42 (42%) and 23 (24%) patients in control and experimental groups, respectively (HR = 0.49; 95% CI: [0.29-0.81]; p = 0.004). Leucopoenia (p = 0.001), thrombocytopenia (p = 0.017) and diarrhea (p = 0.002) occurred more frequently in the experimental group. Reduced-dose tacrolimus with mycophenolate mofetil reduces the occurrence of renal dysfunction and the risk of graft rejection. This immunosuppressive regimen could replace full-dose tacrolimus in adult liver transplantation.
authors.affiliation: Service de Chirurgie Hépatobiliaire et Digestive, Hôpital de Pontchaillou, Centre Hospitalier Universitaire, Rennes, France. karim.boudjema@chu-rennes.fr
authors.forename: K
authors.initials: K
authors.lastname: Boudjema
authors.forename: C
authors.initials: C
authors.lastname: Camus
authors.forename: F
authors.initials: F
authors.lastname: Saliba
authors.forename: Y
authors.initials: Y
authors.lastname: Calmus
authors.forename: E
authors.initials: E
authors.lastname: Salamé
authors.forename: G
authors.initials: G
authors.lastname: Pageaux
authors.forename: C
authors.initials: C
authors.lastname: Ducerf
authors.forename: C
authors.initials: C
authors.lastname: Duvoux
authors.forename: C
authors.initials: C
authors.lastname: Mouchel
authors.forename: A
authors.initials: A
authors.lastname: Renault
authors.forename: P
authors.initials: P
authors.lastname: Compagnon
authors.forename: R
authors.initials: R
authors.lastname: Lorho
authors.forename: E
authors.initials: E
authors.lastname: Bellissant
mesh_terms: D000328:Adult; D048909:Diabetes Complications / Q000276:immunology; D003967:Diarrhea / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D005260:Female; D005602:France; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D006973:Hypertension / Q000209:etiology; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007668:Kidney / Q000503:physiopathology; D007970:Leukopenia / Q000139:chemically induced; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D011446:Prospective Studies; D016559:Tacrolimus / Q000008:administration & dosage*; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus