Everolimus in de Novo Liver Transplantation: a Multicentre Randomized Study

Liver Cirrhosis Clinical Trial

— EPOCAL  

Official title:

Terapia Con Everolimus Nel Trapianto de Novo di Fegato: Uno Studio Multicentrico Randomizzato

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01423708
• Other study ID #: 1956P
• Secondary ID: 2009-016176-78
• Status: Recruiting
• Phase: Phase 2
• First received: August 25, 2011
• Last updated: July 17, 2012
• Start date: February 2010
• Est. completion date: January 2014

Study information

• Verified date: July 2012
• Source: Azienda Ospedaliera di Padova
• Contact: Umberto Cillo, MD
• Phone: +390498218624
• Email: cillo[@]unipd.it
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 117
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Liver Cirrhosis
• Liver Diseases
• Liver Failure
• Liver Neoplasms

Intervention

Drug:
• Everolimus
Administration of Everolimus within 24 hours from the time of randomization (7 days from the time of transplantation) in association with Tacrolimus and steroids. The first dose level of the trough will be performed at day 7 after initiation of therapy. After the reaching an Everolimus trough level of >5ng/ml (final target 6-12 ng/ml), there will be a gradual weaning of tacrolimus (bringing Tacrolimus blood levels <5 ng/ml) with discontinuation of Tacrolimus within 30 days after transplantation when possible.

Locations

Country	Name	City	State
Italy	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

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Ospedaliera di Padova

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Biopsy-proven rejection episodes (BPAR)		3 months	No
Primary	Graft survival		3 months	Yes
Primary	Patient post-Liver Transplantation survival		3 months	Yes
Primary	Everolimus monotherapy	Patients not requiring calcineurin inhibitors (CNI)	30 days	No
Secondary	Renal function evaluation	Impact of therapy on renal function, evaluated by creatinine clearance according to the Modification of Diet in Renal Disease (MDRD) Study.	24 months	No
Secondary	Requests for dialysis		24 months	No
Secondary	Incidence of Adverse Events	Evaluation of common post Liver Transplantation Adverse Events: wound healing, bone marrow depression, hyperlipidemia, proteinuria, diabetes mellitus, diagnosed hypertension, infections, levels of HCV.	24 months	No

External Links

•   Hepatobiliary surgery and Liver Transplantation Unit, University Hospital of Padua (Italy)