OSAKA Trial: A randomized, controlled trial comparing tacrolimus QD and BD in kidney transplantation.
Albano L, Banas B, et al.Transplantation 2013;96(10):897-903
Aims
To assess the noninferiority of tacrolimus once daily (QD) versus tacrolimus twice daily (BD) in renal transplant recipients.
Interventions
Patients received one of four treatments, an initial dose of 1) tacrolimus BD 0.2mg/kg per day, 2) QD 0.2mg/kg per day, 3) QD 0.3mg/kg per day all with mycophenolate mofetil (MMF) and corticosteroids, or 4) tacrolimus QD 0.2mg/kg per day with MMF, basiliximab and corticosteroids given only perioperatively.
Participants
1214 adults with end stage renal disease undergoing primary kidney transplantation or retransplantation.
Outcomes
The primary outcomes included graft loss, biopsy confirmed acute rejection (BCAR), graft dysfunction. The secondary outcomes included eGFR and creatinine clearance, assessment of BCAR, and graft and patient survival.
Follow-up
24 weeks.
CET Conclusions
The OSAKA trial was a large four arm trial with around 300 patients in each arm of the trial as defined above. This was a non inferiority trial but using a composite end point defined as graft loss, biopsy confirmed acute rejection or graft dysfunction at week 4, graft dysfunction being an estimated GFR or less that 40 ml/min. The trial was designed to be a non inferiority trial with the non inferiority margin being set at 12.5%. However one is always concerned at these composite endpoints rather than looking at individual outcomes, but basically tacrolimus given once daily at 0.2mg/kg was probably not inferior to the same dose of tacrolimus being given once a day. Nor was 0.3 mg/kg daily superior to 0.2mg/kg once daily. Renal function was poorest in the steroid avoidance arm of the trial which the authors felt was predominantly associated with more ECD organ donors. Thus this is further evidence that once daily tacrolimus is as satisfactory as twice daily tacrolimus.
Data analysis
Per protocol analysis
Trial registration
ClinicalTrials.gov - NCT00717470