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

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 38 ng/ml throughout the study. Tacrolimus trough targets were 47 ng/ml during the first 3 months and 1.53 ng/ml (n = 107) or 47 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 1.53 ng/ml versus the 47 ng/ml group. Secondary endpoints included incidence of biopsy-proven acute rejection (BPAR; Months 412) and serious adverse events (SAEs; Months 012). 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 1.53 ng/ml: 3.4 +/- 1.4; tacrolimus 47 ng/ml: 5.5 +/- 2.0 ng/ml). BPAR (months 412) 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 1.53 ng/ml tacrolimus group was not achieved. (ClinicalTrials.gov: NCT00369161) is registered at .