Tacrolimus once daily (ADVAGRAF) versus twice daily (PROGRAF) in de novo renal transplantation: a randomized phase III study.
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.
Krämer
B K
BK
V. Medizinische Klinik, Universitätsklinikum Mannheim, University of Heidelberg, Mannheim, Germany. Bernhard.Kraemer@umm.de
Charpentier
B
B
Bäckman
L
L
Silva
H Tedesco
HT
Mondragon-Ramirez
G
G
Cassuto-Viguier
E
E
Mourad
G
G
Sola
R
R
Rigotti
P
P
Mirete
J Ortuno
JO
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
D003692:Delayed-Action Preparations; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus