AUTHOR=Budde Klemens , Rostaing Lionel , Maggiore Umberto , Piotti Giovanni , Surace Daniela , Geraci Silvia , Procaccianti Claudio , Nicolini Gabriele , Witzke Oliver , Kamar Nassim , Albano Laetitia , Büchler Matthias , Pascual Julio , Gutiérrez-Dalmau Alex , Kuypers Dirk , Wekerle Thomas , Głyda Maciej , Carmellini Mario , Tisone Giuseppe , Midtvedt Karsten , Wennberg Lars , Grinyó Josep M. 

TITLE=Prolonged-Release Once-Daily Formulation of Tacrolimus Versus Standard-of-Care Tacrolimus in de novo Kidney Transplant Patients Across Europe

JOURNAL=Transplant International

VOLUME=35

YEAR=2022

URL=https://www.frontierspartnerships.org/journals/transplant-international/articles/10.3389/ti.2021.10225

DOI=10.3389/ti.2021.10225

ISSN=1432-2277

ABSTRACT=<p><bold>Background:</bold> Tacrolimus is the calcineurin inhibitor of choice for preventing acute rejection episodes in kidney transplant patients. However, tacrolimus has a narrow therapeutic range that requires regular monitoring of blood concentrations to minimize toxicity. A new once-daily tacrolimus formulation, LCP-tacrolimus (LCPT), has been developed, which uses MeltDose™ drug-delivery technology to control drug release and enhance overall bioavailability. Our study compared dosing of LCPT with current standard-of-care tacrolimus [immediate-release tacrolimus (IR-Tac) or prolonged-release tacrolimus (PR-Tac)] during the 6 months following <italic>de novo</italic> kidney transplantation. Comparisons of graft function, clinical outcomes, safety, and tolerability for LCPT versus IR-Tac/PR-Tac were also performed.</p><p><bold>Methods:</bold> Standard immunological risk patients with end-stage renal disease who had received a <italic>de novo</italic> kidney transplant were randomized (1:1) to LCPT (N = 200) or IR-Tac/PR-Tac (N = 201).</p><p><bold>Results:</bold> Least squares (LS) mean tacrolimus total daily dose from Week 3 to Month 6 was significantly lower for LCPT than for IR-Tac/PR-Tac. Although LS mean tacrolimus trough levels were significantly higher for LCPT than IR-Tac/PR-Tac, tacrolimus trough levels remained within the standard reference range for most patients. There were no differences between the groups in treatment failure measures or safety profile.</p><p><bold>Conclusion:</bold> LCPT can achieve similar clinical outcomes to other tacrolimus formulations, with a lower daily dose.</p><p><bold>Clinical Trial Registration:</bold><ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/" xmlns:xlink="http://www.w3.org/1999/xlink">https://clinicaltrials.gov/</ext-link>, identifier NCT02432833.</p>