A Multicentre, Randomised, Open-label, Controlled, 12-month Follow-up Study to Assess Impact on Renal Function of an Immunosuppression Regimen Based on Tacrolimus Minimisation in Association With Everolimus in de Novo Liver Transplant Recipients.

A multicentre, randomized, open-label, controlled, exploratory clinical trial with 12-months (52 weeks) of follow-up.

Screening Visit - Inclusion Criteria

• Recipients age 18 or over receiving a first liver transplant from a cadaver donor.
• Patients diagnosed with HCC must meet the Milan radiological criteria at the time of transplant (1 nodule ≤5 cm in diameter, or 2-3 nodules, all <3 cm in diameter) - at time of patient's inclusion on the waiting list.

Anh: done.

• Patients who have signed the informed consent to participate in the study.
• Patients who by medical criteria are capable of complying with the study regimen.

Screening Visit - Exclusion Criteria

• Recipients who have received multiple transplants of solid organs or pancreatic islet cells.
• Patients who have previously received an organ or tissue transplant.
• Patients with a combined liver-kidney transplant.
• Recipients of lobes or segments of liver from a live donor.
• A history of malignancy of any organ system in the previous 3 years according to local protocols (regardless of signs of local recurrence or metastasis), other than non-metastasising basal cell carcinoma or squamous cell carcinoma (epidermoid carcinoma) of the skin, or HCC.
• Patients with known hypersensitivity to the drugs used in the study or others of their class, or to any of their excipients.
• Recipients of ABO-incompatible transplants.
• Patients who test positive for HIV.
• Recipients of organs from donors who tested positive for the hepatitis B surface antigen or HIV seropositive.
• Patients with any medical or surgical condition that in the opinion of the investigator may significantly alter the absorption, distribution, metabolism or excretion of the study medication.
• Women of childbearing potential (i.e. women who are not postmenopausal with amenorrhoea of more than 1 year or surgically sterile) who are planning to become pregnant, are pregnant and/or breastfeeding, or who do not wish to use effective contraception, e.g. hormonal contraceptives (implantation, patches, oral) and double-barrier methods (any double combination of: IUD, male or female condoms with spermicidal gel, diaphragm, contraceptive sponge, cervical cap).
• Patients who are taking part in another clinical trial.

Randomisation Visit - Inclusion Criteria

• Functioning allograft at the time of randomisation. A functioning allograft is defined as:

• levels of AST, ALT and total bilirubin ≤ 4 times the upper limit of normal, and
• levels of alkaline phosphatase and GGT ≤ 5 times the upper limit of normal.
• Glomerular filtrate ≥30 mL/min/1.73 m2 (calculated using the MDRD-4 equation).

Randomisation Visit - Exclusion Criteria

• Patients with proteinuria ≥1.0 g/24 hrs confirmed in the urine sample (protein/creatinine ratio) that cannot be explained by immediate post-operative causes.
• Patients with severe hypercholesterolaemia (≥350 mg/dL; ≥9 mmol/L) or severe hypertriglyceridaemia (≥750 mg/dL; ≥8.5 mmol/L).
• Patients with a platelet count ≤50,000/mm3.
• Patients with an absolute neutrophil count ≤1,000/mm3 or WBC count ≤2,000/mm3.
• Patients who cannot take oral medication.
• Patients with clinically significant systemic infection who require active use of intravenous antibiotics.
• Patients who are in intensive care units and require vital support measures such as mechanical ventilation, dialysis, or vasoactive drugs.
• Patients who have required renal replacement therapy in the 7 days prior to randomisation.
• Patients who have had an episode of acute rejection and have required antibody therapy or who have had more than one episode of corticosteroid-sensitive acute rejection.