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Very Early Introduction of Everolimus in De Novo Liver Transplantation: Results of a Multicenter, Prospective, Randomized Trial
Author(s) -
Cillo Umberto,
Saracino Laura,
Vitale Alessandro,
Bertacco Alessandra,
Salizzoni Mauro,
Lupo Francesco,
Colledan Michele,
Corno Vittorio,
Rossi Giorgio,
Reggiani Paolo,
Baccarani Umberto,
Bresàdola Vittorio,
De Carlis Luciano,
Mangoni Iacopo,
Ramirez Morales Raphael,
Agnes Salvatore,
Nure Erida
Publication year - 2019
Publication title -
liver transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.814
H-Index - 150
eISSN - 1527-6473
pISSN - 1527-6465
DOI - 10.1002/lt.25400
Subject(s) - medicine , liver transplantation , discontinuation , transplantation , clinical endpoint , basiliximab , adverse effect , multicenter trial , randomization , everolimus , surgery , renal function , randomized controlled trial , tacrolimus , gastroenterology , urology , multicenter study
Early everolimus (EVR) introduction and tacrolimus (TAC) minimization after liver transplantation may represent a novel immunosuppressant approach. This phase 2, multicenter, randomized, open‐label trial evaluated the safety and efficacy of early EVR initiation. Patients treated with corticosteroids, TAC, and basiliximab were randomized (2:1) to receive EVR (1.5 mg twice daily) on day 8 and to gradually minimize or withdraw TAC when EVR was stable at >5 ng/mL or to continue TAC at 6‐12 ng/mL. The primary endpoint was the proportion of treated biopsy‐proven acute rejection (tBPAR)–free patients at 3 months after transplant. As secondary endpoints, composite tBPAR plus graft/patient loss rate, renal function, TAC discontinuation rate, and adverse events were assessed. A total of 93 patients were treated with EVR, and 47 were controls. After 3 months from transplantation, 87.1% of patients with EVR and 95.7% of controls were tBPAR‐free ( P = 0.09); composite endpoint‐free patients with EVR were 85% (versus 94%; P = 0.15). Also at 3 months, 37.6% patients were in monotherapy with EVR, and the tBPAR rate was 11.4%. Estimated glomerular filtration rate was significantly higher with EVR, as early as 2 weeks after randomization. In the study group, higher rates of dyslipidemia (15% versus 6.4%), wound complication (18.32% versus 0%), and incisional hernia (25.8% versus 6.4%) were observed, whereas neurological disorders were more frequent in the control group (13.9% versus 31.9%; P < 0.05). In conclusion, an early EVR introduction and TAC minimization may represent a suitable approach when immediate preservation of renal function is crucial.