Liver FailurePhase 2EPOCALNCT01423708
Everolimus in de Novo Liver Transplantation: a Multicentre Randomized Study
A Phase 2 study testing Everolimus in people with Liver Failure and Liver Diseases, run by Azienda Ospedaliera di Padova at 7 sites in Italy.
Trial summary
Safety and Efficacy of Everolimus in adult de novo liver transplant recipients. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Liver Failure, Liver Diseases, Liver Cirrhosis
- What is being tested?
- Everolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 117 participants
- Where
- 7 sitesItaly
- Study dates
- Feb 2010to Jan 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 17Show fewer
- 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
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
Italy7 sites, 7 recruiting
- Recruiting
Ospedali Riuniti - Bergamo
Bergamo, BG, 24128
Michele Colledan, MD, +39 035 269111, mcolledan@ospedaliriuniti.bergamo.it
Vittorio Corno, MD, +39 035 269111, vcorno@ospedaliriuniti.bergamo.it
- Recruiting
Irccs Ospedale Maggiore Policlinico Di Milano
Milan, MI, 20122
Giorgio Rossi, MD, +39 02 55031, giorgio.rossi@unimi.it
Paolo Reggiani, MD, +39 02 55031, paolo.reggiani@policlinico.mi.it
- Recruiting
Ospedale Ca' Granda-Niguarda - Milano
Milan, MI, 20162
Luciano De Carlis, MD, +39 02 64441, Luciano.DeCarlis@ospedaleniguarda.it
Jacopo Mangoni, MD, +39 02 64441, jacopo.mangoni@libero.it
- Recruiting
Azienda Ospedaliera di Padova
Padua, PD, 35128
Umberto Cillo, MD, +390498218624, cillo@unipd.it
Laura Saracino, MBS, +390498218624, lasaracino@gmail.com
- Recruiting
Policlinico Universitario Gemelli Di Roma
Roma, RM, 00168
Salvatore Agnes, MD, +39 06 3550 1928, salvatoreagnes@rm.unicatt.it
Erida Nure, MD, +39 06 3550 1928, eridanure@yahoo.it
- Recruiting
A.O. Universitaria S. Giovanni Battista-Molinette Di Torino
Torino, TO, 10126
Mauro Salizzoni, MD, +39 011 633 1633, msalizzoni@molinette.piemonte.it
Francesco Lupo, MD, +39 011 633 1633, flupo@molinette.piemonte.it
- Recruiting
A.O. Universitaria S. Maria Della Misericordia Di Udine
Udine, UD, 33100
Fabio Bresàdola, MD, +39 0432 5521, fabrizio.bresadola@dsc.uniud.it
Umberto Baccarani, MD, +39 0432 5521, umberto.baccarani@dsc.uniud.it
About this study
Official title: Terapia Con Everolimus Nel Trapianto de Novo di Fegato: Uno Studio Multicentrico Randomizzato
Safety and Efficacy of Everolimus in adult de novo liver transplant recipients.
Read the 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.
- Conditions
- Liver Failure, Liver Diseases, Liver Cirrhosis, Liver Neoplasms
- Being tested
- Everolimus
- Keywords
- Liver Transplantation, Graft Rejection, Graft Survival, Transplantation Immunology, Anti-Rejection Therapy, Immunosuppression, Organ Transplantation, Host vs Graft Reaction, Gastroenterology, Hepatology
- Medical subject headings
- Liver Failure, Liver Diseases, Liver Cirrhosis, Liver Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
Also called Certican, Afinitor, Zortress
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.
| Study group | Role | What they receive |
|---|---|---|
| Control | No intervention | 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). |
| Everolimus | Experimental | Administration of Everolimus in association with Tacrolimus and steroids. Receives: Drug: Everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Biopsy-proven rejection episodes (BPAR)
Measured: 3 months
Graft survival
Measured: 3 months
Patient post-Liver Transplantation survival
Measured: 3 months
Everolimus monotherapy
Patients not requiring calcineurin inhibitors (CNI)
Measured: 30 days
Secondary outcomes (3)
Renal function evaluation
Impact of therapy on renal function, evaluated by creatinine clearance according to the Modification of Diet in Renal Disease (MDRD) Study.
Measured: 24 months
Requests for dialysis
Measured: 24 months
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.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2011 (estimated)
- Study startFeb 2010
- Primary completionJan 2014 (estimated)
- Study completionJan 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 117 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Azienda Ospedaliera di Padova
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof. Umberto Cillo, Azienda Ospedaliera di Padova
- Investigators
- Umberto Cillo, MD, Study chair, Azienda Ospedaliera di Padova
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01423708
- Sponsor's protocol ID
- 1956P
- Other IDs
- 2009-016176-78, 2009
- Acronym
- EPOCAL
- Status last verified
- Jul 2012
- First submitted
- 25 Aug 2011
- Last updated
- 18 Jul 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Terapia Con Everolimus Nel Trapianto de Novo di Fegato: Uno Studio Multicentrico Randomizzato
- ClinicalTrials.gov ID
- NCT01423708
- Acronym / sponsor ID
- EPOCAL / 1956P
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 117 participants (estimated)
- Lead sponsor
- Azienda Ospedaliera di PadovaUniversity, hospital or other
- Study start
- Feb 2010
- Primary completion
- Jan 2014 (estimated)
- Study completion
- Jan 2014 (estimated)
- First posted
- 26 Aug 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control | No intervention | –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). |
| Everolimus | Experimental | Drug: EverolimusAdministration of Everolimus in association with Tacrolimus and steroids. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EverolimusAlso: Certican, Afinitor, ZortressAdministration 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. | Drug | Everolimus |
Primary outcome
Biopsy-proven rejection episodes (BPAR)
Time frame: 3 months
Graft survival
Time frame: 3 months
Patient post-Liver Transplantation survival
Time frame: 3 months
Everolimus monotherapy
Time frame: 30 days
Patients not requiring calcineurin inhibitors (CNI)
3 secondary outcomes
Renal function evaluation
Time frame: 24 months
Requests for dialysis
Time frame: 24 months
Incidence of Adverse Events
Time frame: 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2012.
- Hepatobiliary surgery and Liver Transplantation Unit, University Hospital of Padua (Italy)Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Umberto Cillo, MD study chair
Azienda Ospedaliera di Padova
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Everolimus in people with Liver Failure and Liver Diseases, run by Azienda Ospedaliera di Padova at 7 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Jul 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Umberto Cillo, MD (+390498218624, cillo@unipd.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Biopsy-proven rejection episodes (BPAR) (time frame: 3 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jul 2012.