Everolimus in de Novo Liver Transplantation: a Multicentre Randomized Study (EPOCAL)

University of Padua

Status and phase: Unknown; Phase 2

Conditions: Liver Neoplasms; Liver Cirrhosis; Liver Failure; Liver Diseases

Treatments: Drug: Everolimus

Study type: Interventional

Funder types: Other

Identifiers

NCT01423708

2009-016176-78 (EudraCT Number)

1956P

Details and patient eligibility

About

Safety and Efficacy of Everolimus in adult de novo liver transplant recipients.

Full description

This prospective study was designed to evaluate the feasibility and effectiveness of the use of Everolimus in the minimization and possible suspension of calcineurin inhibitors in adult liver transplant patients. The study will take into account a control group (standard immunosuppression with tacrolimus and steroids) after induction with anti-IL2 Antibodies.

Enrollment: 117 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female patients between 18 and 70 years of age,
• Patients undergoing de novo liver transplantation from cadaveric donor with a functional graft at the time of randomization,
• Transplantation from cadaveric donor whole or split liver,
• Patients able to communicate properly with the study investigators, to understand and respond to the needs of the protocol and who have given written consent
• Cold ischemia time <12 hours

Exclusion criteria

• Physical or laboratory abnormalities or mental illness within 2 weeks before randomization such that, in the opinion of the investigator, may interfere with participation in the study
• Women who are pregnant (positive test with hCG values> 5mUI/ml) or breast-feeding
• Women of childbearing potential, with the following exceptions: a) women in menopause (spontaneous amenorrhea for at least 12 months, spontaneous amenorrhea for at least 6 months with FSH levels >40 mIU/ml, surgical bilateral oophorectomy at least 6 weeks before baseline, with or without hysterectomy) b) women who use one or more reliable and approved methods of contraception for the duration of the study and for the three months following discontinuation of study treatment.
• Patients who undergo transplantation or multivisceral transplantation of pancreatic islets, or who have previously undergone organ transplantation or tissue.
• Patients who undergo combined liver-kidney transplantation
• Patients who undergo living donor liver transplantation
• Patients who undergo ABO-incompatible liver transplantation
• Patients who undergo transplantation from donors positive for HBV surface antigen or HIV
• History of malignant disease at any site in the 3 year period prior, regardless of whether or not there is evidence of recurrence or metastasis. (Except non-metastatic skin cancers such as basal cell or squamous cell carcinoma of the skin, or hepatocellular carcinoma)
• Patients receiving other investigational drugs within 4 weeks before baseline or who are currently enrolled in other clinical trials
• Patients who show hypersensitivity to the drug (or drugs similar to Everolimus - Former macrolides) or class or pharmaceutical excipients. Also, when there are contraindications
• A history of coagulopathy or the presence of any medical condition that requires long-term anticoagulant therapy after transplantation (The use of low-dose ASA is admissible)
• Platelet count <=40.000/mm3 or WBC count <2000/mm3 or hemoglobin <=7g/dl at the time of randomization
• Severe systemic infections
• High cholesterol levels (>350mg/dl) or severe hypertriglyceridemia (>500mg/dl). Patients with compensated hyperlipidemia are eligible.
• Diagnosis of pre-transplant autoimmune liver disease (PBC, sclerosing cholangitis)
• Acute Liver Failure

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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117 participants in 2 patient groups

Control

No Intervention group

Description:

Standard immunosuppression protocol with Tacrolimus, maintaining trough levels between 6 and 12 ng/ml in the first month, in association with steroids (20 mg/day with subsequent weaning within 3 months after transplantation).

Everolimus

Experimental group

Description:

Administration of Everolimus in association with Tacrolimus and steroids.

Treatment:

Drug: Everolimus