Sustained Virological Response (SVR) to Antiviral Treatment of Liver Transplant Recipients With Recurrent Hepatitis C (SUSTAIN)

Novartis

Status and phase: Completed; Phase 4

Conditions: Liver Transplantation; Hepatitis C

Treatments: Drug: tacrolimus (Prograf); Drug: cyclosporin (Neoral)

Study type: Interventional

Funder types: Industry

Identifiers

NCT00938860

COLO400A2430

2009-010806-12

Details and patient eligibility

About

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.

Enrollment: 92 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

92 participants in 2 patient groups

Neoral

Experimental group

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

Treatment:

Drug: cyclosporin (Neoral)

tacrolimus

Active Comparator group

Description:

Tacrolimus capsules bid, doses were adjusted as necessary to achieve and maintain recommended C0 target ranges.

Treatment:

Drug: tacrolimus (Prograf)