Everolimus in de Novo Liver Transplantation: a Multicentre Randomized Study

Phase 2

• Conditions: Liver Failure; Liver Diseases; Liver Cirrhosis; Liver Neoplasms
• Interventions: Drug: Everolimus

• Registration Number: NCT01423708
• Lead Sponsor: Azienda Ospedaliera di Padova

Brief Summary

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

Detailed 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.

Study Timeline

• Study Start: 2010-02
• Study First Submitted: 2011-08-25
• Study First Submitted QC: 2011-08-25
• Study First Posted: 2011-08-26
• Status Verified: 2012-07
• Last Update Submitted: 2012-07-17
• Last Update Posted: 2012-07-18
• Primary Completion: 2014-01
• Study Completion: 2014-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 117

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Everolimus	Everolimus	Administration of Everolimus in association with Tacrolimus and steroids.

Primary Outcome Measures

Name	Time	Method
Biopsy-proven rejection episodes (BPAR)	3 months
Graft survival	3 months
Patient post-Liver Transplantation survival	3 months
Everolimus monotherapy	30 days	Patients not requiring calcineurin inhibitors (CNI)

Secondary Outcome Measures

Name	Time	Method
Renal function evaluation	24 months	Impact of therapy on renal function, evaluated by creatinine clearance according to the Modification of Diet in Renal Disease (MDRD) Study.
Requests for dialysis	24 months
Incidence of Adverse Events	24 months	Evaluation of common post Liver Transplantation Adverse Events: wound healing, bone marrow depression, hyperlipidemia, proteinuria, diabetes mellitus, diagnosed hypertension, infections, levels of HCV.

Trial Locations

Locations (7)

Ospedali Riuniti - Bergamo; 🇮🇹 Bergamo, BG, Italy

Irccs Ospedale Maggiore Policlinico Di Milano; 🇮🇹 Milano, MI, Italy

Ospedale Ca' Granda-Niguarda - Milano; 🇮🇹 Milano, MI, Italy

Azienda Ospedaliera di Padova; 🇮🇹 Padua, PD, Italy

Policlinico Universitario Gemelli Di Roma; 🇮🇹 Roma, RM, Italy

A.O. Universitaria S. Giovanni Battista-Molinette Di Torino; 🇮🇹 Torino, TO, Italy

A.O. Universitaria S. Maria Della Misericordia Di Udine; 🇮🇹 Udine, UD, Italy