title: Tacrolimus once daily (ADVAGRAF) versus twice daily (PROGRAF) in de novo renal transplantation: a randomized phase III study.
abstract: This multicenter, 1:1-randomized, parallel-group, noninferiority study compared the efficacy and safety of twice-daily tacrolimus (Tacrolimus BID; Prograf) and once-daily tacrolimus prolonged release (Tacrolimus QD; Advagraf), combined with steroids and low-dose mycophenolate mofetil without antibody induction, in 667 de novo kidney transplant recipients. A double-blind, double-dummy 24-week period was followed by an open extension of up to 12 months posttransplant. Biopsy-proven acute rejection rate at 24 weeks (primary endpoint, per-protocol analysis) was 15.8% for Tacrolimus BID versus 20.4% for Tacrolimus QD (p = 0.182; treatment difference 4.5%, 95% confidence interval-1.8%, 10.9%, just outside the prespecified 10% noninferiority margin). Kaplan-Meier 12-month patient and graft survival rates were 97.5% and 92.8% for Tacrolimus BID and 96.9% and 91.5% for QD. Both treatment groups showed equally well-maintained renal function at 12 months (mean creatinine clearance approximately 67 mL/min) and similar adverse event profiles. Overall results obtained with either Tacrolimus QD or BID, without antibody induction, were good, supporting use of the once-daily formulation as an effective alternative to the established twice-daily formulation.
authors.affiliation: V. Medizinische Klinik, Universitätsklinikum Mannheim, University of Heidelberg, Mannheim, Germany. Bernhard.Kraemer@umm.de
authors.forename: B K
authors.initials: BK
authors.lastname: Krämer
authors.forename: B
authors.initials: B
authors.lastname: Charpentier
authors.forename: L
authors.initials: L
authors.lastname: Bäckman
authors.forename: H Tedesco
authors.initials: HT
authors.lastname: Silva
authors.forename: G
authors.initials: G
authors.lastname: Mondragon-Ramirez
authors.forename: E
authors.initials: E
authors.lastname: Cassuto-Viguier
authors.forename: G
authors.initials: G
authors.lastname: Mourad
authors.forename: R
authors.initials: R
authors.lastname: Sola
authors.forename: P
authors.initials: P
authors.lastname: Rigotti
authors.forename: J Ortuno
authors.initials: JO
authors.lastname: Mirete
mesh_terms: D000328:Adult; D000368:Aged; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D003692:Delayed-Action Preparations; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus