title: Everolimus plus early tacrolimus minimization: a phase III, randomized, open-label, multicentre trial in renal transplantation.
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.
authors.affiliation: Department of Transplantation and Surgery, Semmelweis University, Budapest, Hungary. roblanger@hotmail.com
authors.forename: Robert M
authors.initials: RM
authors.lastname: Langer
authors.forename: Ronald
authors.initials: R
authors.lastname: Hené
authors.forename: Stefan
authors.initials: S
authors.lastname: Vitko
authors.forename: Maarten
authors.initials: M
authors.lastname: Christiaans
authors.forename: Helio
authors.initials: H
authors.lastname: Tedesco-Silva
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Ciechanowski
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Cassuto
authors.forename: Lionel
authors.initials: L
authors.lastname: Rostaing
authors.forename: Mario
authors.initials: M
authors.lastname: Vilatoba
authors.forename: Uwe
authors.initials: U
authors.lastname: Machein
authors.forename: Bettina
authors.initials: B
authors.lastname: Ulbricht
authors.forename: Guido
authors.initials: G
authors.lastname: Junge
authors.forename: Gaohong
authors.initials: G
authors.lastname: Dong
authors.forename: Julio
authors.initials: J
authors.lastname: Pascual
mesh_terms: D000328:Adult; D065095:Calcineurin Inhibitors; D000068338:Everolimus; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology / Q000379:methods* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D000068338:Everolimus; D020123:Sirolimus; D016559:Tacrolimus