title: A randomized trial of everolimus and low-dose cyclosporine in renal transplantation: with or without steroids?
abstract: This multicenter, randomized, prospective, controlled trial (EVIDENCE study) aimed to determine short-term effects of early steroid withdrawal in renal transplant patients initially treated with everolimus, low-dose cyclosporine (CsA), and steroids. Patients were randomized to standard triple therapy with CsA, everolimus twice daily and steroids (group A), steroid-free immunosuppression (group B), or triple therapy once daily (group C). However, since patient enrollment was slower than expected, group C randomization was prematurely discontinued. The primary end point was treatment failure rate (composite end point of death, graft loss, biopsy-proven acute rejection, and loss to follow-up) between randomization and month 12. Patients evaluable for the primary end point included 139 randomized patients. According to intention-to-treat analysis, 2.8% of patients in group A and 14.7% in group B experienced treatment failure (95% upper confidence limit 19.7%). As this was higher than the predefined noninferiority limit of 10%, noninferiority could not be proved. No conclusive statements can be made on noninferiority of the steroid withdrawal regimen vs the standard regimen in these patients. Additional studies with longer follow-up are required to determine the efficacy of steroid-free immunosuppression in renal transplant recipients receiving everolimus.
authors.affiliation: Division of Nephrology, Humanitas Scientific Institute, Rozzano (Mi), Italy. Electronic address: ponticelli.claudio@gmail.com.
authors.forename: C
authors.initials: C
authors.lastname: Ponticelli
authors.affiliation: U.O.C. Chirurgia dei Trapianti Azienda Ospedaliera Universitaria, Senese, Policlinico "Santa Maria alle Scotte," Siena, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Carmellini
authors.affiliation: U.O.C. Trapianti, D'Or gano e Patologie Complesse, Fondazione PTV Policlinico Tor Vergata, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Tisone
authors.affiliation: U.O. Nefrologia, A.O. Spedali Civili di Brescia, Brescia, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Sandrini
authors.affiliation: S.C. Nefrologia Dialisi e Trapianto, A.O.U. San Giovanni Battista di Torino, Torino, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Segoloni
authors.affiliation: SSD Trapianti e Pancreas, Azienda Ospedaliera di Padova, Padova, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Rigotti
authors.affiliation: S.C Nefrologia, Dialisi e Terapia Medica del Trapianto Renale, Azienda Ospedaliera "Niguarda Cà Granda," Milano, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Colussi
authors.affiliation: Dipartimento di Medicina Specialistica Diagnostica e Sperimentale, Alma Mater Studiorum, Università di Bologna, U.O. di Nefrologia Dialisi e Trapianto, Bologna, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Stefoni
mesh_terms: D000328:Adult; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D000068338:Everolimus; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D057194:Intention to Treat Analysis; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D011446:Prospective Studies; D020123:Sirolimus / Q000031:analogs & derivatives; D017211:Treatment Failure
chemical_list: D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D020123:Sirolimus; D008775:Methylprednisolone