title: Once-daily prolonged-release tacrolimus (ADVAGRAF) versus twice-daily tacrolimus (PROGRAF) in liver transplantation.
abstract: The efficacy and safety of dual-therapy regimens of twice-daily tacrolimus (BID; Prograf) and once-daily tacrolimus (QD; Advagraf) administered with steroids, without antibody induction, were compared in a multicenter, 1:1-randomized, two-arm, parallel-group study in 475 primary liver transplant recipients. A double-blind, double-dummy 24-week period was followed by an open extension to 12 months posttransplant. The primary endpoint, event rate of biopsy-proven acute rejection (BPAR) at 24 weeks, was 33.7% for tacrolimus BID versus 36.3% for tacrolimus QD (Per-protocol set; p = 0.512; treatment difference 2.6%, 95% confidence interval -7.3%, 12.4%), falling within the predefined 15% noninferiority margin. At 12 months, BPAR episodes requiring treatment were similar for tacrolimus BID and QD (28.1% and 24.7%). Twelve-month patient and graft survival was 90.8% and 85.6% for tacrolimus BID and 89.2% and 85.3% for tacrolimus QD. Adverse event (AE) profiles were similar for both tacrolimus BID and QD with comparable incidences of AEs and serious AEs. Tacrolimus QD was well tolerated with similar efficacy and safety profiles to tacrolimus BID.
authors.affiliation: Department of Hepatogastroenterology, IKEM, Prague, Czech Republic. patr@medicon.cz
authors.forename: P
authors.initials: P
authors.lastname: Trunečka
authors.forename: O
authors.initials: O
authors.lastname: Boillot
authors.forename: D
authors.initials: D
authors.lastname: Seehofer
authors.forename: A D
authors.initials: AD
authors.lastname: Pinna
authors.forename: L
authors.initials: L
authors.lastname: Fischer
authors.forename: B-G
authors.initials: BG
authors.lastname: Ericzon
authors.forename: R I
authors.initials: RI
authors.lastname: Troisi
authors.forename: U
authors.initials: U
authors.lastname: Baccarani
authors.forename: J
authors.initials: J
authors.lastname: Ortiz de Urbina
authors.forename: W
authors.initials: W
authors.lastname: Wall
mesh_terms: D000328:Adult; D005260:Female; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007677:Kidney Function Tests; D016031:Liver Transplantation / Q000276:immunology / Q000379:methods*; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus