Everolimus in de Novo Liver Transplantation: a Multicentre Randomized Study

NCT ID: NCT01423708

Last Updated: 2012-07-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

117 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-02-28

Study Completion Date

2014-01-31

Brief Summary

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

Detailed Description

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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

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Liver Failure Liver Diseases Liver Cirrhosis Liver Neoplasms

Keywords

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Liver Transplantation Graft Rejection Graft Survival Transplantation Immunology Anti-Rejection Therapy Immunosuppression Organ Transplantation Host vs Graft Reaction Gastroenterology Hepatology

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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).

Group Type NO_INTERVENTION

No interventions assigned to this group

Everolimus

Administration of Everolimus in association with Tacrolimus and steroids.

Group Type EXPERIMENTAL

Everolimus

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

Other Intervention Names

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Certican Afinitor Zortress

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Azienda Ospedaliera di Padova

OTHER

Sponsor Role lead

Responsible Party

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Prof. Umberto Cillo

Director of the Hepatobiliary Surgery and Liver Transplantation Unit

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Umberto Cillo, MD

Role: STUDY_CHAIR

Azienda Ospedaliera di Padova

Locations

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Ospedali Riuniti - Bergamo

Bergamo, BG, Italy

Site Status RECRUITING

Irccs Ospedale Maggiore Policlinico Di Milano

Milan, MI, Italy

Site Status RECRUITING

Ospedale Ca' Granda-Niguarda - Milano

Milan, MI, Italy

Site Status RECRUITING

Azienda Ospedaliera di Padova

Padua, PD, Italy

Site Status RECRUITING

Policlinico Universitario Gemelli Di Roma

Roma, RM, Italy

Site Status RECRUITING

A.O. Universitaria S. Giovanni Battista-Molinette Di Torino

Torino, TO, Italy

Site Status RECRUITING

A.O. Universitaria S. Maria Della Misericordia Di Udine

Udine, UD, Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Umberto Cillo, MD

Role: CONTACT

Phone: +390498218624

Email: [email protected]

Laura Saracino, MSc

Role: CONTACT

Phone: +390498218624

Email: [email protected]

Facility Contacts

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Michele Colledan, MD

Role: primary

Vittorio Corno, MD

Role: backup

Giorgio Rossi, MD

Role: primary

Paolo Reggiani, MD

Role: backup

Luciano De Carlis, MD

Role: primary

Jacopo Mangoni, MD

Role: backup

Umberto Cillo, MD

Role: primary

Laura Saracino, MBS

Role: backup

Salvatore Agnes, MD

Role: primary

Erida Nure, MD

Role: backup

Mauro Salizzoni, MD

Role: primary

Francesco Lupo, MD

Role: backup

Fabio Bresàdola, MD

Role: primary

Umberto Baccarani, MD

Role: backup

Related Links

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http://www.fegatochirurgia.com/

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

Other Identifiers

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2009-016176-78

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1956P

Identifier Type: -

Identifier Source: org_study_id