The purpose of this study was, starting from the Italian clinical practice in liver transplantation, to optimize the immunosuppressive therapy, considering specific patient characteristics as alcoholic cirrhosis, hepatitis C virus (HCV), hepatocellular carcinoma (HCC), and short/long-term implications. Then efficacy and safety of a calcineurin inhibitor (CNI)-withdrawal regimen was evaluated in comparison with a CNI-minimization regimen.

Inclusion criteria at Baseline:

• Male and female liver transplant recipients who are ≥ 18 years of age, treated with a tacrolimus-based immunosuppressive regimen, who have received an induction therapy or i.v. steroids as per local clinical practice.
• Recipients of a full-size or technically modified liver allograft will be eligible at 4 weeks (± 7 days) after liver transplantation.
• Allograft is functioning at an acceptable level by the time of Baseline as defined by the AST, ALT, total bilirubin levels ≤ 3 times ULN and INR < 1.5 times ULN.
• Abbreviated MDRD-4 eGFR ≥ 30 mL/min/1.73m2. Serum creatinine results obtained within 5 days prior to Baseline are acceptable.

Inclusion criteria at Randomization:

• Effective tacrolimus minimization, confirmed by stable blood trough levels in the two months prior to randomization, i.e. verification of last two tacrolimus blood trough level ≤ 5 ng/mL in the two months prior to randomization. Investigators should make adjustments in tacrolimus dosing to continue to target trough levels ≤ 5 ng/mL prior to randomization.
• Abbreviated MDRD-4 eGFR ≥ 30 mL/min/1.73m2. Serum creatinine results obtained within 5 days prior to Visit 5 are acceptable.

Exclusion criteria at Baseline:

• Patients who are recipients of multiple solid organ transplants, (e.g., multivisceral or combined liver-kidney transplants), or have previously received an organ or tissue transplanted, or who received an AB0 incompatible transplant.
• Patients who experienced more than one episode of treated biopsy proven acute rejection (BANFF ≥ 3 or RAI ≥ 7) or one steroid-resistant acute rejection.
• Patients who require renal replacement therapy.
• Patients with a confirmed spot urine protein/creatinine ratio that indicates ≥1.0 g/24 hrs of proteinuria.
• History of malignancy of any organ system within the past 5 years whether or not there is evidence of local recurrence or metastases, other than non-metastatic basal or squamous cell carcinoma of the skin or HCC.

Exclusion criteria at Randomization:

• Patients who experienced more than two episodes of treated biopsy proven acute rejection (BANFF ≥ 3 or RAI ≥ 7) since transplantation or one steroid-resistant acute rejection during the run-in period.
• Patients with a confirmed spot urine protein/creatinine ratio that indicates ≥ 3.0 g/24 hrs of proteinuria.

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Run-in Population: all consented and everolimus-treated patients who entered the run-in treatment period.

All 78 enrolled patients were included in the run-in treatment period. Treatment started at the randomization period.

Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.