Everolimus in de Novo Liver Transplantation: a Multicentre Randomized Study

NCT01423708 | Unknown Phase 2 DMC

• 2 other identifiers: 1956P2009-016176-78
• Study Type: interventional
• Target: 117
• Locations: 1 country
• Sites: 7

Brief Summary

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

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; Gastroenterology; Hepatology

Outcome Measures

Primary Outcomes (4)

• Biopsy-proven rejection episodes (BPAR)

  3 months

• Graft survival

  3 months

• Patient post-Liver Transplantation survival

  3 months

• Everolimus monotherapy

  Patients not requiring calcineurin inhibitors (CNI)

  30 days

Secondary Outcomes (3)

• Renal function evaluation

  24 months

• Requests for dialysis

  24 months

• Incidence of Adverse Events

  24 months

Study Arms (2)

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.

Drug: Everolimus

Interventions

Everolimus 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.

Also known as: Certican, Afinitor, Zortress

Everolimus

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Azienda Ospedaliera di Padova: lead

Study Sites (7)

Ospedali Riuniti - Bergamo

Bergamo, BG, 24128, Italy

RECRUITING

Irccs Ospedale Maggiore Policlinico Di Milano

Milan, MI, 20122, Italy

RECRUITING

Ospedale Ca' Granda-Niguarda - Milano

Milan, MI, 20162, Italy

RECRUITING

Azienda Ospedaliera di Padova

Padua, PD, 35128, Italy

RECRUITING

Policlinico Universitario Gemelli Di Roma

Roma, RM, 00168, Italy

RECRUITING

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

Torino, TO, 10126, Italy

RECRUITING

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

Udine, UD, 33100, Italy

RECRUITING

Related Links

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

MeSH Terms

Conditions

Liver Failure; Liver Diseases; Liver Cirrhosis; Liver Neoplasms

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Hepatic Insufficiency; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Umberto Cillo, MD

  Azienda Ospedaliera di Padova

  STUDY CHAIR

Central Study Contacts

Umberto Cillo, MD

CONTACT

+390498218624; cillo@unipd.it

Laura Saracino, MSc

CONTACT

+390498218624; lasaracino@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the Hepatobiliary Surgery and Liver Transplantation Unit

Study Record Dates

• First Submitted: August 25, 2011
• First Posted: August 26, 2011
• Study Start: February 1, 2010
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: July 18, 2012

Record last verified: 2012-07

Locations

IT (7)