Sustained Virological Response (SVR) to Antiviral Treatment of Liver Transplant Recipients With Recurrent Hepatitis C
Condition: Hepatitis C; Liver Transplantation
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis
Intervention: cyclosporin (Neoral); tacrolimus (Prograf)
Intervention description: Neoral capsules bid, Doses were to be adjusted as necessary to achieve and maintain recommended C0 (monitoring of trough levels) or C2 concentration 2 hours post dosing) target ranges; Tacrolimus capsules bid, doses were adjusted as necessary to achieve and maintain recommended C0 target ranges.
Intervention MeSH terms: Cyclosporine; Tacrolimus; Cyclosporins
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 92.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Hepatitis C; liver transplantation; anti-viral therapy

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