Novel Once-Daily Extended-Release Tacrolimus Versus Twice-Daily Tacrolimus in De Novo Kidney Transplant Recipients: Two-Year Results of Phase 3, Double-Blind, Randomized Trial.
| Autor: | Rostaing L; University Hospital Toulouse-Rangueil, Toulouse, France. Electronic address: rostaing.l@chu-toulouse.fr., Bunnapradist S; David Geffen School of Medicine at UCLA, Los Angeles, CA., Grinyó JM; Hospital Universitari de Bellvitge, Catalunya, Spain., Ciechanowski K; Pomeranian Medical University, Szczecin, Poland., Denny JE; Henry Ford Hospital, Detroit, MI., Silva HT Jr; Hospital do Rim e Hipertensao, Sao Paulo, Brazil., Budde K; Department of Nephrology, Charité Universitätsmedizin, Berlin, Germany. |
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| Jazyk: | angličtina |
| Zdroj: | American journal of kidney diseases : the official journal of the National Kidney Foundation [Am J Kidney Dis] 2016 Apr; Vol. 67 (4), pp. 648-59. Date of Electronic Publication: 2015 Dec 22. |
| DOI: | 10.1053/j.ajkd.2015.10.024 |
| Abstrakt: | Background: 1-year data from this trial showed the noninferiority of a novel once-daily extended-release tacrolimus (LCPT; Envarsus XR) to immediate-release tacrolimus (IR-Tac) twice daily after kidney transplantation. Study Design: Final 24-month analysis of a 2-armed, parallel-group, randomized, double-blind, double-dummy, multicenter, phase 3 trial. Setting & Participants: 543 de novo kidney recipients randomly assigned to LCPT (n=268) or IR-Tac (n=275); 507 (93.4%) completed the 24-month study. Intervention: LCPT tablets once daily at 0.17 mg/kg/d or IR-Tac twice daily at 0.1 mg/kg/d; subsequent doses were adjusted to maintain target trough ranges (first 30 days, 6-11 ng/mL; thereafter, 4-11 ng/mL). The intervention was 24 months; the study was double blinded for the entirety. Outcomes & Measurements: Treatment failure (death, transplant failure, biopsy-proven acute rejection, or loss to follow up) within 24 months. Safety end points included adverse events, serious adverse events, new-onset diabetes, kidney function, opportunistic infections, and malignancies. Pharmacokinetic measures included total daily dose (TDD) of study drugs and tacrolimus trough levels. Results: 24-month treatment failure was LCPT, 23.1%; IR-Tac, 27.3% (treatment difference, -4.14% [95% CI, -11.38% to +3.17%], well below the +10% noninferiority criterion defined for the primary 12-month end point). Subgroup analyses showed fewer treatment failures for LCPT versus IR-Tac among black, older, and female recipients. Safety was similar between groups. From month 1, TDD was lower for LCPT; the difference increased over time. At month 24, mean TDD for LCPT was 24% lower than for the IR-Tac group (P<0.001), but troughs were similar (means at 24 months: LCPT, 5.47 ± 0.17 ng/mL; IR-Tac, 5.8 ± 0.30 ng/mL; P=0.4). Limitations: Trial participant eligibility criteria may limit the generalizability of results to the global population of de novo kidney transplant recipients. Conclusions: Results suggest that once-daily LCPT in de novo kidney transplantation has comparable efficacy and safety profile to that of IR-Tac. Lower TDD reflects LCPT's improved bioavailability and absorption. (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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