Clinical trial NCT00582738: Efficacy of Everolimus as Inhibitor of Fibrosis Progression in Liver Transplant Patients With Recurrence of Hepatitis C Viral Infection
Official title: A Randomized, Controlled, Open Label, Two Arms, Exploratory Study to Evaluate the Effect of Everolimus on Histologically Assessed Fibrosis Progression (Ishak-Knodell) in Liver Transplant Recipients With Recurrent Hepatitis C Viral Infection as Compared to Standard Treatment.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Recurrent Hepatitis C
Keywords: Fibrosis progression
recurrent hepatitis C
viral infection
liver transplant recipients
everolimus
Hepatitis C recurrence after orthotopic liver transplantation (OLT)
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2007-12-28
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will assess the efficacy of everolimus as an inhibitor of fibrosis progression in liver transplant patients who have a recurrence of hepatitis C viral infection in the transplant


Eligibility criteria: Inclusion Criteria:

* Male or female patients 18 - 65 years of age
* Recipients of deceased or living donors
* Patients who had undergone primary liver transplantation at least 6 months before enrolment
* Recurrent Hepatitis C viral infection and histologically confirmed liver fibrosis (stage I-IV in the Ishak-Knodell scale) obtained at baseline or within the previous 6 months to the date of enrolment
* Patients receiving tacrolimus or cyclosporine micro-emulsion with or without - Mycophenolic acid (MPA), with or without steroids.
* Absence of acute rejection episodes within the previous 6 months to the date of enrolment
* Patient in whom an allograft biopsy will not be contraindicated
* Patient willing and capable of giving written informed consent for study participation and able to participate in the study for 24 months
* Patients with Hepatocellular carcinoma (HCC) within the University California, San Francisco (UCSF) Criteria and no recurrence for at least 18 months after OLT.

Exclusion Criteria:

* Recipients of multiple organ transplants or patients who have undergone retransplantation
* Current biliary complications
* History of drug or alcohol abuse within 1 year before enrolment
* Patients treated with anti-hepatitis C virus treatment at the time of enrollment or within the previous month to the date of enrolment
* Co-infection with Hepatitis B virus (HBV) or Human Immunodeficiency Virus (HIV)
* Patients with Leukocyte count (WBC) \< 3000/mm3, platelet count \< 75000/mm3 or Hemoglobin (Hb) \< 8 g/dl
* Patients with proteinuria \>1g/24 hours
* Patient with a current severe systemic infection

Other protocol defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Change From Baseline in Fibrosis Staging Score (Measured by the Ishak-Knodell Staging Score) Between Baseline and 24 Months Post-transplant.
timeFrame: baseline, 24 Months
Secondary outcomes:
measure: Change From Baseline in Fibrosis Metavir Scoring at 12 and 24 Months Post Randomization
timeFrame: Baseline, 12 months, 24 months
measure: Percentage of Patients With Death, Graft Loss and Biopsy Proven Acute Rejection (BPAR) Between Study Groups
timeFrame: 24 Months
measure: Number of Patients With Events (Progression to Cirrhosis, Retransplantation, HCV Related Death, First BPAR, Graft Loss)at 12 and 24 Months
timeFrame: 12 months, 24 months
measure: Comparison of Renal Function (Glomerular Filtration Rate [GFR] Calculated Using the Modification of Diet in Renal Disease Study Group [MDRD] Formula) Between Study Groups
timeFrame: 12 months, 24 months/EOS
measure: Comparison of the Effect of Both Regimens in the Necroinflammatory Grading Score (Ishak-Knodell) (Portal Inflammation)
timeFrame: baseline, 12 months, 24 months
measure: Comparison of the Effect of Both Regimens on the Inflammatory (Acti-test) and Fibrosis (Fibro-test) Components of Fibrosure, and on Fibrosis Area Assessed by Histomorphometry
timeFrame: baseline, 12 and 24 months
measure: Percentage of Patients in Each Study Arm With Increase of ≥1 Point in the Ishak-Knodell Staging Score in Fibrosis
timeFrame: baseline to month 24
measure: Change From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at 12 and 24 Months Post Randomization
timeFrame: baseline, 12 months, 24 months/EOS
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Novartis Investigative site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: