Clinical trial NCT00938860: Sustained Virological Response (SVR) to Antiviral Treatment of Liver Transplant Recipients With Recurrent Hepatitis C
Official title: A Multi-center, Randomized, Open Label, Controlled Study to Compare the Sustained Virological Response During Treatment With Neoral or Tacrolimus in Maintenance Liver Transplant Recipients Treated With Pegylated Interferon and Ribavirin for Recurrent Hepatitis C
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hepatitis C
Liver Transplantation
Keywords: Hepatitis C
liver transplantation
anti-viral therapy
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2009-07-14
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will assess the rates of Sustained Virological Response following anti-viral therapy with Peg-Interferon plus Ribavirin in patients that have been liver transplanted with recurrent Hepatitis C and treated with Neoral or tacrolimus.


Eligibility criteria: Inclusion criteria:

* Liver transplantation performed at least 6 months and up to 5 years prior randomization and due to HCV cirrhosis, with or without pre-transplant hepatocellular carcinoma (HCC) within Milan or UCSF criteria
* Immunosuppresive regimen based on tacrolimus b.i.d.- (twice or once daily) for at least 6 months prior randomization
* Diagnosis of HCV genotypes 1 or 4 infection prior to transplantationconfirmed at screening
* Indication of treatment with Peg-IFN and ribavirin due to histological evidence of chronic HCV infection defined as a fibrosis stage equal or greater than 1 using the Ishak-Knodell scoring system (IK ≥1) in a liver biopsy performed at screening or up to 4 months prior to randomization.

Exclusion criteria:

* Serum creatinine \>150 μmol/L (1.6 7 mg/dL) or eGFR \< 50 ml/min (4-variable Modification of Diet in Renal Disease \[MDRD Cockcroft-Gault formula\])
* Multi-organ transplant recipients
* Recent episode of steroid-treated acute rejection (AR) within 3 months prior to randomization, or \>1 episode of steroid-treated AR in the last 6 months, or any number of steroid-resistant AR episodes in the last 6 months including evidence of chronic rejection or ductopenia
* Evidence of conditions that could cause graft dysfunction other than HCV infection
* Patients with signs of decompensated liver disease, defined as presence of ascites, variceal bleeding, encephalopathy or deteriorated hepatic synthetic function (albumin \<3.5g/dL or, total direct bilirubin \>1.5mg/dL or, INR \>1.5)
* Co-infection with HIV or Hepatitis B (defined as HBsAg-positive) at screening
* Use of mTOR inhibitors (everolimus or sirolimus) in the 6 months prior to screening
* Antiviral treatment for HCV administered at any time after liver transplantation
* Patients on daily doses of corticosteroids higher than 5 mg/day
* Patients with fibrosing cholestatic hepatitis
* Patients with current diagnosis of malignancies, including lymphoproliferative disorders
* Patients with platelet count \<70,000/mm3 or neutrophiles \<1,500/mm3
* History of HCC outside Milan criteria based on radiology or UCSF criteria based on analysis of the explant

Primary outcomes:
measure: Number of Participants Sustained Virological Response (SVR) Following Treatment of Hepatitis C Virus (HCV) Infection With Peg-IFN and Ribavirin in Liver Transplanted Recipients on Maintenance Therapy With Neoral or Tacrolimus
timeFrame: Week 24
Secondary outcomes:
measure: Number of Events of the Composite Endpoint of Biopsy Proven Acute Rejections (BPAR), Death or Graft Loss and of the Individual Components
timeFrame: Week 80
measure: Number of Participants With Fibrosis Progression (Increase in Ishak-Knodell (IK) Score by at Least One Point From the Baseline)
timeFrame: Week 80
measure: Number of Participants of Rapid Viral Response (RVR)
timeFrame: Week 4
measure: Number of Participants of Early Viral Response (EVR)
timeFrame: Week 12
measure: Number of Participants for the End of Treatment Response (ETR)
timeFrame: Week 80
measure: Number of Participants of True Non-responder Rate
timeFrame: Week 80
measure: Number of Participants for Relapse Rate
timeFrame: Week 24
measure: Number of Participants With Dose Reduction or Discontinuation of Antiviral (AV) Therapy Due to Poor Tolerability at Any Time During the Study for Any Reason
timeFrame: Week 80
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Novartis Investigative Site
state: Arizona
city: Palo Alto
country: United States
facility: Novartis Investigative Site
state: California
city: San Francisco
country: United States
facility: Novartis Investigative Site
state: California
city: Gainesville
country: United States
facility: Novartis Investigative Site
state: Florida
city: Chapel Hill
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Oklahoma City
country: United States
facility: Novartis Investigative Site
state: Oklahoma
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Madison
country: United States
facility: Novartis Investigative Site
state: Wisconsin
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Fortaleza
country: Brazil
facility: Novartis Investigative Site
state: CE
city: São Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Edmonton
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: Vancouver
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Winnipeg
country: Canada
facility: Novartis Investigative Site
state: Manitoba
city: London
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Bogotá
country: Colombia
facility: Novartis Investigative Site
state: Cundinamarca
city: Bogotá
country: Colombia
facility: Novartis Investigative Site
city: Creteil
country: France
facility: Novartis Investigative Site
city: Lyon Cedex 04
country: France
facility: Novartis Investigative Site
city: Montpellier
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Toulouse Cedex 4
country: France
facility: Novartis Investigative Site
city: Villejuif
country: France
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Bologna
country: Italy
facility: Novartis Investigative Site
state: BO
city: Padova
country: Italy
facility: Novartis Investigative Site
state: PD
city: Udine
country: Italy
facility: Novartis Investigative Site
state: UD
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Oviedo
country: Spain
facility: Novartis Investigative Site
state: Asturias
city: Valladolid
country: Spain
facility: Novartis Investigative Site
state: Castilla y Leon
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Santiago de Compostela
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Zurich
country: Switzerland
facility: Novartis Investigative Site
city: Birmingham
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: