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

R. 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

Research output: Article

80 Citations (Scopus)

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 - máj. 2012

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Tacrolimus
Kidney Transplantation
Multicenter Studies
Kidney
Everolimus
Glomerular Filtration Rate
Adrenal Cortex Hormones
Transplants
Biopsy
Safety
Incidence

ASJC Scopus subject areas

  • Transplantation

Cite this

Everolimus plus early tacrolimus minimization : A phase III, randomized, open-label, multicentre trial in renal transplantation. / Langer, R.; Hené, Ronald; Vitko, Stefan; Christiaans, Maarten; Tedesco-Silva, Helio; Ciechanowski, Kazimierz; Cassuto, Elisabeth; Rostaing, Lionel; Vilatoba, Mario; MacHein, Uwe; Ulbricht, Bettina; Junge, Guido; Dong, Gaohong; Pascual, Julio.

In: Transplant International, Vol. 25, No. 5, 05.2012, p. 592-602.

Research output: Article

Langer, R, 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, vol. 25, no. 5, pp. 592-602. https://doi.org/10.1111/j.1432-2277.2012.01465.x
Langer, R. ; Hené, Ronald ; Vitko, Stefan ; Christiaans, Maarten ; Tedesco-Silva, Helio ; Ciechanowski, Kazimierz ; Cassuto, Elisabeth ; Rostaing, Lionel ; Vilatoba, Mario ; MacHein, Uwe ; Ulbricht, Bettina ; Junge, Guido ; Dong, Gaohong ; Pascual, Julio. / Everolimus plus early tacrolimus minimization : A phase III, randomized, open-label, multicentre trial in renal transplantation. In: Transplant International. 2012 ; Vol. 25, No. 5. pp. 592-602.
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AU - Tedesco-Silva, Helio

AU - Ciechanowski, Kazimierz

AU - Cassuto, Elisabeth

AU - Rostaing, Lionel

AU - Vilatoba, Mario

AU - MacHein, Uwe

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