Tacrolimus Once Daily (ADVAGRAF) Versus Twice Daily (PROGRAF) in De Novo Renal Transplantation: A Randomized Phase III Study
2010 (English)In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 10, no 12, 2632-2643 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2010. Vol. 10, no 12, 2632-2643 p.
Biopsy-proven acute rejection, immunosuppression, kidney transplantation, noninferiority study, prolonged-release tacrolimus, tacrolimus
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-140144DOI: 10.1111/j.1600-6143.2010.03256.xISI: 000284698400014PubMedID: 20840480OAI: oai:DiVA.org:uu-140144DiVA: diva2:383149