Clinical trial NCT01423708: Everolimus in de Novo Liver Transplantation: a Multicentre Randomized Study
Official title: Terapia Con Everolimus Nel Trapianto de Novo di Fegato: Uno Studio Multicentrico Randomizzato
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Liver Failure
Liver Diseases
Liver Cirrhosis
Liver Neoplasms
Keywords: Liver Transplantation
Graft Rejection
Graft Survival
Transplantation Immunology
Anti-Rejection Therapy
Immunosuppression
Organ Transplantation
Host vs Graft Reaction
Gastroenterology
Hepatology
Lead sponsor: Azienda Ospedaliera di Padova
Sponsor class: OTHER
First posted: 2011-08-26
Enrollment: 117
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Biopsy-proven rejection episodes (BPAR)
timeFrame: 3 months
measure: Graft survival
timeFrame: 3 months
measure: Patient post-Liver Transplantation survival
timeFrame: 3 months
measure: Everolimus monotherapy
timeFrame: 30 days
Secondary outcomes:
measure: Renal function evaluation
timeFrame: 24 months
measure: Requests for dialysis
timeFrame: 24 months
measure: Incidence of Adverse Events
timeFrame: 24 months
Other outcomes:
Locations:
city: Bergamo
country: Italy
facility: Ospedali Riuniti - Bergamo
state: BG
city: Milano
country: Italy
facility: Irccs Ospedale Maggiore Policlinico Di Milano
state: MI
city: Milano
country: Italy
facility: Ospedale Ca' Granda-Niguarda - Milano
state: MI
city: Padua
country: Italy
facility: Azienda Ospedaliera di Padova
state: PD
city: Roma
country: Italy
facility: Policlinico Universitario Gemelli Di Roma
state: RM
city: Torino
country: Italy
facility: A.O. Universitaria S. Giovanni Battista-Molinette Di Torino
state: TO
city: Udine
country: Italy
facility: A.O. Universitaria S. Maria Della Misericordia Di Udine
state: UD
Study officials:
affiliation: Azienda Ospedaliera di Padova
name: Umberto Cillo, MD
role: STUDY_CHAIR
References: