Everolimus plus early tacrolimus minimization: A phase III, randomized, open-label, multicentre trial in renal transplantation

Robert M. Langer, Ronald Hené, Stefan Vitko, Maarten Christiaans, Helio Tedesco-Silva, Kazimierz Ciechanowski, Elisabeth Cassuto, Lionel Rostaing, Mario Vilatoba, Uwe MacHein, Bettina Ulbricht, Guido Junge, Gaohong Dong, Julio Pascual

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Abstract

There is increasing interest in tacrolimus-minimization regimens. ASSET was an open-label, randomized, 12-month study of everolimus plus tacrolimus in de-novo renal-transplant recipients. Everolimus trough targets were 3-8 ng/ml throughout the study. Tacrolimus trough targets were 4-7 ng/ml during the first 3 months and 1.5-3 ng/ml (n = 107) or 4-7 ng/ml (n = 117) from Month 4. All patients received basiliximab induction and corticosteroids. The primary objective was to demonstrate superior estimated glomerular filtration rate (eGFR; MDRD-4) at Month 12 in the tacrolimus 1.5-3 ng/ml versus the 4-7 ng/ml group. Secondary endpoints included incidence of biopsy-proven acute rejection (BPAR; Months 4-12) and serious adverse events (SAEs; Months 0-12). Statistical significance was not achieved for the primary endpoint (mean eGFR: 57.1 vs. 51.7 ml/min/1.73 m 2), potentially due to overlapping of achieved tacrolimus exposure levels (Month 12 mean ± SD, tacrolimus 1.5-3 ng/ml: 3.4 ± 1.4; tacrolimus 4-7 ng/ml: 5.5 ± 2.0 ng/ml). BPAR (months 4-12) and SAE rates were comparable between groups (2.7% vs. 1.1% and 58.7% vs. 51.3%; respectively). Everolimus-facilitated tacrolimus minimization, to levels lower than previously investigated, achieved good renal function, low BPAR and graft-loss rates, and an acceptable safety profile in renal transplantation over 12 months although statistically superior renal function of the 1.5-3 ng/ml tacrolimus group was not achieved. (ClinicalTrials.gov: NCT00369161) is registered at.

Original languageEnglish
Pages (from-to)592-602
Number of pages11
JournalTransplant International
Volume25
Issue number5
DOIs
Publication statusPublished - May 1 2012

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Keywords

  • calcineurin inhibitor minimization
  • everolimus
  • mammalian target of rapamycin inhibitor
  • proliferation signal inhibitors
  • tacrolimus

ASJC Scopus subject areas

  • Transplantation

Cite this

Langer, R. M., Hené, R., Vitko, S., Christiaans, M., Tedesco-Silva, H., Ciechanowski, K., Cassuto, E., Rostaing, L., Vilatoba, M., MacHein, U., Ulbricht, B., Junge, G., Dong, G., & Pascual, J. (2012). Everolimus plus early tacrolimus minimization: A phase III, randomized, open-label, multicentre trial in renal transplantation. Transplant International, 25(5), 592-602. https://doi.org/10.1111/j.1432-2277.2012.01465.x