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Tacrolimus Once Daily (ADVAGRAF) Versus Twice Daily (PROGRAF) in De Novo Renal Transplantation: A Randomized Phase III Study
Author(s) -
Krämer B. K.,
Charpentier B.,
Bäckman L.,
Silva Jr H. Tedesco,
MondragonRamirez G.,
CassutoViguier E.,
Mourad G.,
Sola R.,
Rigotti P.,
Mirete J. Ortuno
Publication year - 2010
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2010.03256.x
Subject(s) - tacrolimus , medicine , urology , adverse effect , renal function , clinical endpoint , kidney transplantation , transplantation , confidence interval , creatinine , randomized controlled trial , surgery
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.