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

Primary Purpose

Liver Failure, Liver Diseases, Liver Cirrhosis

Status
Unknown status
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Everolimus
Sponsored by
Azienda Ospedaliera di Padova
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Liver Failure focused on measuring Liver Transplantation, Graft Rejection, Graft Survival, Transplantation Immunology, Anti-Rejection Therapy, Immunosuppression, Organ Transplantation, Host vs Graft Reaction, Gastroenterology, Hepatology

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Ospedali Riuniti - BergamoRecruiting
  • Irccs Ospedale Maggiore Policlinico Di MilanoRecruiting
  • Ospedale Ca' Granda-Niguarda - MilanoRecruiting
  • Azienda Ospedaliera di PadovaRecruiting
  • Policlinico Universitario Gemelli Di RomaRecruiting
  • A.O. Universitaria S. Giovanni Battista-Molinette Di TorinoRecruiting
  • A.O. Universitaria S. Maria Della Misericordia Di UdineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

Control

Everolimus

Arm 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).

Administration of Everolimus in association with Tacrolimus and steroids.

Outcomes

Primary Outcome Measures

Biopsy-proven rejection episodes (BPAR)
Graft survival
Patient post-Liver Transplantation survival
Everolimus monotherapy
Patients not requiring calcineurin inhibitors (CNI)

Secondary Outcome Measures

Renal function evaluation
Impact of therapy on renal function, evaluated by creatinine clearance according to the Modification of Diet in Renal Disease (MDRD) Study.
Requests for dialysis
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.

Full Information

First Posted
August 25, 2011
Last Updated
July 17, 2012
Sponsor
Azienda Ospedaliera di Padova
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1. Study Identification

Unique Protocol Identification Number
NCT01423708
Brief Title
Everolimus in de Novo Liver Transplantation: a Multicentre Randomized Study
Acronym
EPOCAL
Official Title
Terapia Con Everolimus Nel Trapianto de Novo di Fegato: Uno Studio Multicentrico Randomizzato
Study Type
Interventional

2. Study Status

Record Verification Date
July 2012
Overall Recruitment Status
Unknown status
Study Start Date
February 2010 (undefined)
Primary Completion Date
January 2014 (Anticipated)
Study Completion Date
January 2014 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Azienda Ospedaliera di Padova

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
117 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Control
Arm Type
No Intervention
Arm 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).
Arm Title
Everolimus
Arm Type
Experimental
Arm Description
Administration of Everolimus in association with Tacrolimus and steroids.
Intervention Type
Drug
Intervention Name(s)
Everolimus
Other Intervention Name(s)
Certican, Afinitor, Zortress
Intervention Description
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.
Primary Outcome Measure Information:
Title
Biopsy-proven rejection episodes (BPAR)
Time Frame
3 months
Title
Graft survival
Time Frame
3 months
Title
Patient post-Liver Transplantation survival
Time Frame
3 months
Title
Everolimus monotherapy
Description
Patients not requiring calcineurin inhibitors (CNI)
Time Frame
30 days
Secondary Outcome Measure Information:
Title
Renal function evaluation
Description
Impact of therapy on renal function, evaluated by creatinine clearance according to the Modification of Diet in Renal Disease (MDRD) Study.
Time Frame
24 months
Title
Requests for dialysis
Time Frame
24 months
Title
Incidence of Adverse Events
Description
Evaluation of common post Liver Transplantation Adverse Events: wound healing, bone marrow depression, hyperlipidemia, proteinuria, diabetes mellitus, diagnosed hypertension, infections, levels of HCV.
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Umberto Cillo, MD
Phone
+390498218624
Email
cillo@unipd.it
First Name & Middle Initial & Last Name or Official Title & Degree
Laura Saracino, MSc
Phone
+390498218624
Email
lasaracino@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Umberto Cillo, MD
Organizational Affiliation
Azienda Ospedaliera di Padova
Official's Role
Study Chair
Facility Information:
Facility Name
Ospedali Riuniti - Bergamo
City
Bergamo
State/Province
BG
ZIP/Postal Code
24128
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michele Colledan, MD
Phone
+39 035 269111
Email
mcolledan@ospedaliriuniti.bergamo.it
First Name & Middle Initial & Last Name & Degree
Vittorio Corno, MD
Phone
+39 035 269111
Email
vcorno@ospedaliriuniti.bergamo.it
First Name & Middle Initial & Last Name & Degree
Michele Colledan, MD
First Name & Middle Initial & Last Name & Degree
Vittorio Corno, MD
Facility Name
Irccs Ospedale Maggiore Policlinico Di Milano
City
Milano
State/Province
MI
ZIP/Postal Code
20122
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Giorgio Rossi, MD
Phone
+39 02 55031
Email
giorgio.rossi@unimi.it
First Name & Middle Initial & Last Name & Degree
Paolo Reggiani, MD
Phone
+39 02 55031
Email
paolo.reggiani@policlinico.mi.it
First Name & Middle Initial & Last Name & Degree
Giorgio Rossi, MD
First Name & Middle Initial & Last Name & Degree
Paolo Reggiani, MD
Facility Name
Ospedale Ca' Granda-Niguarda - Milano
City
Milano
State/Province
MI
ZIP/Postal Code
20162
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Luciano De Carlis, MD
Phone
+39 02 64441
Email
Luciano.DeCarlis@ospedaleniguarda.it
First Name & Middle Initial & Last Name & Degree
Jacopo Mangoni, MD
Phone
+39 02 64441
Email
jacopo.mangoni@libero.it
First Name & Middle Initial & Last Name & Degree
Luciano De Carlis, MD
First Name & Middle Initial & Last Name & Degree
Jacopo Mangoni, MD
Facility Name
Azienda Ospedaliera di Padova
City
Padua
State/Province
PD
ZIP/Postal Code
35128
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Umberto Cillo, MD
Phone
+390498218624
Email
cillo@unipd.it
First Name & Middle Initial & Last Name & Degree
Laura Saracino, MBS
Phone
+390498218624
Email
lasaracino@gmail.com
First Name & Middle Initial & Last Name & Degree
Umberto Cillo, MD
First Name & Middle Initial & Last Name & Degree
Giacomo Zanus, MD
First Name & Middle Initial & Last Name & Degree
Daniele Neri, MD
First Name & Middle Initial & Last Name & Degree
Patrizia Boccagni, MD
First Name & Middle Initial & Last Name & Degree
Francesco D'Amico, MD
First Name & Middle Initial & Last Name & Degree
Enrico Gringeri, MD
First Name & Middle Initial & Last Name & Degree
Alessandro Vitale, MD
First Name & Middle Initial & Last Name & Degree
Pasquale Bonsignore, MD
First Name & Middle Initial & Last Name & Degree
Paolo Feltracco, MD
First Name & Middle Initial & Last Name & Degree
Dino Sgarabotto, MD
First Name & Middle Initial & Last Name & Degree
Roberto Marchini, MD
First Name & Middle Initial & Last Name & Degree
Angelica Magrofuoco, CCTC
First Name & Middle Initial & Last Name & Degree
Laura Saracino, MSc
Facility Name
Policlinico Universitario Gemelli Di Roma
City
Roma
State/Province
RM
ZIP/Postal Code
00168
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Salvatore Agnes, MD
Phone
+39 06 3550 1928
Email
salvatoreagnes@rm.unicatt.it
First Name & Middle Initial & Last Name & Degree
Erida Nure, MD
Phone
+39 06 3550 1928
Email
eridanure@yahoo.it
First Name & Middle Initial & Last Name & Degree
Erida Nure, MD
First Name & Middle Initial & Last Name & Degree
Salvatore Agnes, MD
Facility Name
A.O. Universitaria S. Giovanni Battista-Molinette Di Torino
City
Torino
State/Province
TO
ZIP/Postal Code
10126
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mauro Salizzoni, MD
Phone
+39 011 633 1633
Email
msalizzoni@molinette.piemonte.it
First Name & Middle Initial & Last Name & Degree
Francesco Lupo, MD
Phone
+39 011 633 1633
Email
flupo@molinette.piemonte.it
First Name & Middle Initial & Last Name & Degree
Mauro Salizzoni, MD
First Name & Middle Initial & Last Name & Degree
Francesco Lupo, MD
Facility Name
A.O. Universitaria S. Maria Della Misericordia Di Udine
City
Udine
State/Province
UD
ZIP/Postal Code
33100
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fabio Bresàdola, MD
Phone
+39 0432 5521
Email
fabrizio.bresadola@dsc.uniud.it
First Name & Middle Initial & Last Name & Degree
Umberto Baccarani, MD
Phone
+39 0432 5521
Email
umberto.baccarani@dsc.uniud.it
First Name & Middle Initial & Last Name & Degree
Umberto Baccarani, MD
First Name & Middle Initial & Last Name & Degree
Fabio Bresàdola, MD

12. IPD Sharing Statement

Links:
URL
http://www.fegatochirurgia.com/
Description
Hepatobiliary surgery and Liver Transplantation Unit, University Hospital of Padua (Italy)

Learn more about this trial

Everolimus in de Novo Liver Transplantation: a Multicentre Randomized Study

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