Conflicts of Interest The authors of this manuscript have no conflicts of interest to disclose.
Everolimus plus early tacrolimus minimization: a phase III, randomized, open-label, multicentre trial in renal transplantation
Article first published online: 26 MAR 2012
© 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation
Volume 25, Issue 5, pages 592–602, May 2012
How to Cite
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. and Pascual, J. (2012), Everolimus plus early tacrolimus minimization: a phase III, randomized, open-label, multicentre trial in renal transplantation. Transplant International, 25: 592–602. doi: 10.1111/j.1432-2277.2012.01465.x
- Issue published online: 4 APR 2012
- Article first published online: 26 MAR 2012
- Received: 28 October 2011 Revision requested: 21 November 2011 Accepted: 22 February 2012
- calcineurin inhibitor minimization;
- mammalian target of rapamycin inhibitor;
- proliferation signal inhibitors;
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 m2), 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 http://www.clinicaltrials.gov.