This Phase III randomized trial examined efficacy and safety of a novel once-daily extended-release tacrolimus formulation (LCP-Tacro [LCPT]) versus twice-daily tacrolimus in de novo kidney transplantation. Primary efficacy end point was proportion of patients with treatment failure (death, graft failure, biopsy-proven acute rejection or lost to follow-up) within 12 months. Starting doses were, LCPT: 0.17 mg/kg/day and tacrolimus twice-daily: 0.1 mg/kg/day; 543 patients were randomized, LCPT: n ¼ 268; tacrolimus twice-daily: n ¼ 275. At 12 months treatment failure was LCPT: 18.3% and tacrolimus twice-daily: 19.6%; the upper 95% CI of the treatment difference was þ5.27%, below the predefined þ10% noninferiority criteria. There were no significant differences in the incidence of individual efficacy events or adverse events. Target tacrolimus trough levels were more rapidly achieved in the LCPT group. Following initial dose, 36.6% of patients in the LCPT group had rapidly attained trough levels within 6-11 ng/mL versus 18.5% of tacrolimus twice-daily patients; majority of tacrolimus twice-daily patients (74.7%) had troughs <6 ng/mL compared with 33.5% in the LCPT group. Overall, cumulative study dose was 14% lower for LCPT. Results suggest that use of oncedaily LCPT in de novo kidney transplantation is efficacious and safe. Lower LCPT dose reflects the improved absorption provided by the novel formulation.

Once-daily tacrolimus extended-release formulation (Prograf XL,

Planned conversion from tacrolimus to sirolimus was evaluated in de novo kidney transplant recipients. In this multicenter, randomized, open-label study, 297 patients were initially treated with tacrolimus, mycophenolate sodium and prednisone. Of the 283 patients reaching 3 months, 97 were converted to sirolimus (SRL), 107 were maintained on tacrolimus (TAC) and 79 were patients receiving TAC without criteria to undergo intervention at month 3 (TACex). The primary objective was to show superior estimated glomerular filtration rate (eGFR) in the SRL group at month 24. Of the 258 patients who completed 24 months, 91 (94%) were in the SRL group, 101 (94%) in the TAC group and 66 (84%) in the TACex group. In the intention-to-treat population there were no differences in eGFR (66.2 AE 25.3 vs. 70.7 AE 25.1, p ¼ 0.817) or in the severity of chronic sclerosing lesions scores in 24-month protocol biopsies. Higher mean urinary protein-tocreatinine ratio (0.36 AE 0.69 vs. 0.15 AE 0.53, p ¼ 0.03) and higher incidence of treated acute rejection between months 3-24 (13.4% vs. 4.7%, p ¼ 0.047) were observed in SRL compared to TAC group. In this population planned conversion from TAC to SRL 3 months after kidney transplantation was not associated with improved renal function at 24 months.

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