Novel Once-Daily Extended-Release Tacrolimus (LCPT) Versus Twice-Daily Tacrolimus in De Novo Kidney Transplants: One-Year Results of Phase III, Double-Blind, Randomized Trial

被引:94
作者
Budde, K. [1 ]
Bunnapradist, S. [2 ]
Grinyo, J. M. [3 ]
Ciechanowski, K. [4 ]
Denny, J. E. [5 ]
Silva, H. T. [6 ]
Rostaing, L. [7 ]
机构
[1] Charite, Dept Nephrol, D-13353 Berlin, Germany
[2] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA
[3] Hosp Univ Bellvitge, Dept Nephrol, Catalunya, Spain
[4] Pomeranian Med Univ, Dept Nephrol & Transplantat, Szczecin, Poland
[5] Henry Ford Hosp, Henry Ford Transplant Inst, Detroit, MI 48202 USA
[6] Hosp Rim & Hipertensao, Dept Nephrol, Sao Paulo, Brazil
[7] Univ Hosp Toulouse Rangueil, Dept Nephrol & Transplantat, Toulouse, France
关键词
calcineurin inhibitor: tacrolimus; clinical research; practice; clinical trial; immunosuppressant; immunosuppression; immune modulation; kidney transplantation; nephrology; OPEN-LABEL; A-DAY; RENAL-TRANSPLANTATION; PHARMACOKINETICS; CAPSULES; SAFETY; MULTICENTER; CONVERSION; FREQUENCY; REJECTION;
D O I
10.1111/ajt.12955
中图分类号
R61 [外科手术学];
学科分类号
摘要
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: 0.17mg/kg/day and tacrolimus twice-daily: 0.1mg/kg/day; 543 patients were randomized, LCPT: n=268; tacrolimus twice-daily: n=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 +5.27%, below the predefined +10% 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 6-11ng/mL versus 18.5% of tacrolimus twice-daily patients; majority of tacrolimus twice-daily patients (74.7%) had troughs <6ng/mL compared with 33.5% in the LCPT group. Overall, cumulative study dose was 14% lower for LCPT. Results suggest that use of once-daily LCPT in de novo kidney transplantation is efficacious and safe. Lower LCPT dose reflects the improved absorption provided by the novel formulation. One-year results from this Phase III randomized, double-blind trial show that novel once-daily extended-release tacrolimus formulation affords rapid achievement of therapeutic tacrolimus trough levels, and it has noninferior efficacy and similar safety and renal function outcomes as twice-daily tacrolimus in de novo kidney transplant recipients, at a lower tacrolimus dose
引用
收藏
页码:2796 / 2806
页数:11
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