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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2012 by Azienda Ospedaliera di Padova.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Prof. Umberto Cillo, Azienda Ospedaliera di Padova
ClinicalTrials.gov Identifier:
NCT01423708
First received: August 25, 2011
Last updated: July 17, 2012
Last verified: July 2012
  Purpose

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


Condition Intervention Phase
Liver Failure
Liver Diseases
Liver Cirrhosis
Liver Neoplasms
Drug: Everolimus
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Terapia Con Everolimus Nel Trapianto de Novo di Fegato: Uno Studio Multicentrico Randomizzato

Resource links provided by NLM:


Further study details as provided by Azienda Ospedaliera di Padova:

Primary Outcome Measures:
  • Biopsy-proven rejection episodes (BPAR) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Graft survival [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
  • Patient post-Liver Transplantation survival [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
  • Everolimus monotherapy [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    Patients not requiring calcineurin inhibitors (CNI)


Secondary Outcome Measures:
  • Renal function evaluation [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Impact of therapy on renal function, evaluated by creatinine clearance according to the Modification of Diet in Renal Disease (MDRD) Study.

  • Requests for dialysis [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Incidence of Adverse Events [ Time Frame: 24 months ] [ Designated as safety issue: No ]

    Evaluation of common post Liver Transplantation Adverse Events:

    wound healing, bone marrow depression, hyperlipidemia, proteinuria, diabetes mellitus, diagnosed hypertension, infections, levels of HCV.



Estimated Enrollment: 117
Study Start Date: February 2010
Estimated Study Completion Date: January 2014
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Control
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).
Experimental: Everolimus
Administration of Everolimus in association with Tacrolimus and steroids.
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.
Other Names:
  • Certican
  • Afinitor
  • Zortress

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

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01423708

Contacts
Contact: Umberto Cillo, MD +390498218624 cillo@unipd.it
Contact: Laura Saracino, MSc +390498218624 lasaracino@gmail.com

Locations
Italy
Ospedali Riuniti - Bergamo Recruiting
Bergamo, BG, Italy, 24128
Contact: Michele Colledan, MD    +39 035 269111    mcolledan@ospedaliriuniti.bergamo.it   
Contact: Vittorio Corno, MD    +39 035 269111    vcorno@ospedaliriuniti.bergamo.it   
Principal Investigator: Michele Colledan, MD         
Sub-Investigator: Vittorio Corno, MD         
Irccs Ospedale Maggiore Policlinico Di Milano Recruiting
Milano, MI, Italy, 20122
Contact: Giorgio Rossi, MD    +39 02 55031    giorgio.rossi@unimi.it   
Contact: Paolo Reggiani, MD    +39 02 55031    paolo.reggiani@policlinico.mi.it   
Principal Investigator: Giorgio Rossi, MD         
Sub-Investigator: Paolo Reggiani, MD         
Ospedale Ca` Granda-Niguarda - Milano Recruiting
Milano, MI, Italy, 20162
Contact: Luciano De Carlis, MD    +39 02 64441    Luciano.DeCarlis@ospedaleniguarda.it   
Contact: Jacopo Mangoni, MD    +39 02 64441    jacopo.mangoni@libero.it   
Principal Investigator: Luciano De Carlis, MD         
Sub-Investigator: Jacopo Mangoni, MD         
Azienda Ospedaliera di Padova Recruiting
Padua, PD, Italy, 35128
Contact: Umberto Cillo, MD    +390498218624    cillo@unipd.it   
Contact: Laura Saracino, MBS    +390498218624    lasaracino@gmail.com   
Principal Investigator: Umberto Cillo, MD         
Sub-Investigator: Giacomo Zanus, MD         
Sub-Investigator: Daniele Neri, MD         
Sub-Investigator: Patrizia Boccagni, MD         
Sub-Investigator: Francesco D'Amico, MD         
Sub-Investigator: Enrico Gringeri, MD         
Sub-Investigator: Alessandro Vitale, MD         
Sub-Investigator: Pasquale Bonsignore, MD         
Sub-Investigator: Paolo Feltracco, MD         
Sub-Investigator: Dino Sgarabotto, MD         
Sub-Investigator: Roberto Marchini, MD         
Sub-Investigator: Angelica Magrofuoco, CCTC         
Sub-Investigator: Laura Saracino, MSc         
Policlinico Universitario Gemelli Di Roma Recruiting
Roma, RM, Italy, 00168
Contact: Salvatore Agnes, MD    +39 06 3550 1928    salvatoreagnes@rm.unicatt.it   
Contact: Erida Nure, MD    +39 06 3550 1928    eridanure@yahoo.it   
Sub-Investigator: Erida Nure, MD         
Principal Investigator: Salvatore Agnes, MD         
A.O. Universitaria S. Giovanni Battista-Molinette Di Torino Recruiting
Torino, TO, Italy, 10126
Contact: Mauro Salizzoni, MD    +39 011 633 1633    msalizzoni@molinette.piemonte.it   
Contact: Francesco Lupo, MD    +39 011 633 1633    flupo@molinette.piemonte.it   
Principal Investigator: Mauro Salizzoni, MD         
Sub-Investigator: Francesco Lupo, MD         
A.O. Universitaria S. Maria Della Misericordia Di Udine Recruiting
Udine, UD, Italy, 33100
Contact: Fabio Bresàdola, MD    +39 0432 5521    fabrizio.bresadola@dsc.uniud.it   
Contact: Umberto Baccarani, MD    +39 0432 5521    umberto.baccarani@dsc.uniud.it   
Sub-Investigator: Umberto Baccarani, MD         
Principal Investigator: Fabio Bresàdola, MD         
Sponsors and Collaborators
Azienda Ospedaliera di Padova
Investigators
Study Chair: Umberto Cillo, MD Azienda Ospedaliera di Padova
  More Information

Additional Information:
No publications provided

Responsible Party: Prof. Umberto Cillo, Director of the Hepatobiliary Surgery and Liver Transplantation Unit, Azienda Ospedaliera di Padova
ClinicalTrials.gov Identifier: NCT01423708     History of Changes
Other Study ID Numbers: 1956P, 2009-016176-78
Study First Received: August 25, 2011
Last Updated: July 17, 2012
Health Authority: Italy: Ethics Committee

Keywords provided by Azienda Ospedaliera di Padova:
Liver Transplantation
Graft Rejection
Graft Survival
Transplantation Immunology
Anti-Rejection Therapy
Immunosuppression
Organ Transplantation
Host vs Graft Reaction
Gastroenterology
Hepatology

Additional relevant MeSH terms:
Liver Diseases
Liver Cirrhosis
Liver Failure
Liver Neoplasms
Digestive System Diseases
Hepatic Insufficiency
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Everolimus
Sirolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents

ClinicalTrials.gov processed this record on September 29, 2014