title: OSAKA trial: a randomized, controlled trial comparing tacrolimus QD and BD in kidney transplantation.
abstract: BACKGROUND
  The once-daily (QD), prolonged-release formulation of tacrolimus has been shown to improve adherence versus twice-daily (BD) tacrolimus. Treatment nonadherence in transplant recipients has been associated with poor graft outcomes.
  
  
  METHODS
  This open-label, parallel-group study randomized adults with end-stage renal disease undergoing primary kidney transplantation or retransplantation to an initial dose of tacrolimus BD 0.2 mg/kg per day (Arm 1; n=309), QD 0.2 mg/kg per day (Arm 2; n=302), QD 0.3 mg/kg per day (Arm 3; n=304) all with mycophenolate mofetil and corticosteroids (tapered) over 24 weeks, or tacrolimus QD 0.2 mg/kg per day with mycophenolate mofetil, basiliximab, and corticosteroids given only perioperatively (Arm 4; n=283). The primary composite endpoint (efficacy failure; per protocol set) was defined as graft loss, biopsy-confirmed acute rejection, or graft dysfunction at week 24. Graft dysfunction was defined as estimated glomerular filtration rate Modification of Diet in Renal Disease-4 formula of less than 40 mL/min/1.73 m(2). The prespecified noninferiority margin was 12.5%.
  
  
  RESULTS
  The per protocol set included 976 patients: 237, 263, 246, and 230 patients in Arms 1 to 4, respectively. Noninferiority of the composite endpoint was demonstrated for Arm 2 versus Arm 1; Kaplan-Meier estimates of efficacy failure were 42.2% and 40.6%, respectively (difference, -1.6%; 95% confidence interval [CI], -12.2% to 9.0%). Noninferiority to Arm 1 was not confirmed for Arm 3 (difference, -3.5%; 95% CI, -13.6% to 6.6%) or Arm 4 (difference, -7.1%; 95% CI, -16.1% to 1.9%). Graft dysfunction (estimated glomerular filtration rate <40 mL/min/1.73 m(2)) was the main determinant of composite-endpoint efficacy failure across all arms.
  
  
  CONCLUSIONS
  In patients representative of the European kidney transplant population, tacrolimus QD-based immunosuppression (0.2 mg/kg/day), without induction, showed similar efficacy to 0.2 mg/kg per day tacrolimus BD.
authors: 1 Department of Nephrology, Centre Hospitalier Universitaire de Nice, Nice, France. 2 Internal Medicine II-Nephrology, University Medical Center, Regensburg, Germany. 3 General, Visceral and Transplantation Surgery, Hannover Medical School, Hannover, Germany. 4 Department of Transplantology and Surgery, District Public Hospital, Poznan, Poland. 5 Department of Nephrology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. 6 Department of Nephrology, Dialysis and Organ Transplantation, Toulouse University Hospital, Toulouse, France. 7 Address correspondence to: Nassim Kamar, M.D., Department of Nephrology, Dialysis and Organ Transplantation, Toulouse University Hospital, CHU Rangueil TSA 50032, 31059 Toulouse Cedex 9, France.
authors: Laetitia
authors: L
authors: Albano
authors: Bernhard
authors: B
authors: Banas
authors: Juergen L
authors: JL
authors: Klempnauer
authors: Maciej
authors: M
authors: Glyda
authors: Ondrej
authors: O
authors: Viklicky
authors: Nassim
authors: N
authors: Kamar
mesh_terms: D000328:Adult; D001706:Biopsy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007676:Kidney Failure, Chronic / Q000601:surgery*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus
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