Tacrolimus (TAC) is available as a twice-daily capsule (TAC-BID), once-daily capsule (TAC-QD), and once-daily tablet. Recipients with ABO-incompatible/anti-human leukocyte antigen (HLA)-incompatible transplantation were excluded in previous trials and have thus not been evaluated. We conducted a 5-year trial to determine whether TAC-QD is noninferior to TAC-BID for transplant outcomes. Adults who underwent de novo living kidney transplantation were randomly assigned (62 TAC-QD; 63 TAC-BID). We did not exclude ABO-/HLA- incompatible transplantation. TAC was initiated 7 days preoperatively (0.10 mg/kg/d). Mycophenolate mofetil, methylprednisolone, and basiliximab were administered. The primary endpoint was graft failure (non-censored for death). We performed a noninferiority test. The noninferiority margin was 10% in risk difference. Five-year graft failure rates were 6.5% and 9.5% for TAC-QD and TAC-BID, respectively (noninferiority, P = 0.009). The estimated glomerular filtration rates were similar between the groups (noninferiority, P < 0.001). TAC-QD did not have point estimates of risk difference above the inferiority margin in any assessed endpoints. However, a tendency of interaction was observed between biopsy-proven acute rejection and the follow-up period. In a living kidney transplant population with 40% of patients with ABO/HLA incompatibility, the effect of TAC-QD was not appreciably worse on various clinical transplant outcomes than that of TAC-BID over 5 years.
Keywords: kidney transplantation; long-term outcomes; randomized noninferiority trial; tacrolimus formulation.
© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.