Liver Fibrosis in Patients Transplanted for Hepatitis C Receiving Either Cyclosporine Microemulsion or Tacrolimus

Novartis

Status and phase: Terminated; Phase 4

Conditions: Hepatitis C; Liver Transplant

Treatments: Drug: Tacrolimus; Drug: Cyclosporine A

Study type: Interventional

Funder types: Industry

Identifiers

NCT00260208

COLO400A2426

Details and patient eligibility

About

Following a transplant for hepatitis C cirrhosis, the infection comes back in 70-90% of cases and over time causes fibrosis and eventually cirrhosis of the new liver. The aim of this study was to see if the frequency of liver fibrosis was different with cyclosporine microemulsion than tacrolimus

Enrollment: 361 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria

• Reason for transplant is end-stage liver disease due to hepatitis C cirrhosis
• Patients receiving a first liver transplant from a deceased or living donor
• Patients in whom biopsies will be possible

Exclusion criteria

• Recipients of a liver from an hepatitis C virus positive (HCV+), human immunodeficiency virus positive (HIV+) or hepatitis B virus positive (HBV+) donor
• Patients with any severe coexisting disease or suffering any unstable medical condition or co-infected with HBV or HIV
• Patients with co-existing alcoholic disease who have not been abstinent for at least 6 months
• Transplanted for liver cancer exceeding a pre-defined size
• Pregnant or nursing women

Other protocol-defined inclusion/exclusion criteria may apply

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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361 participants in 2 patient groups

Cyclosporin A

Active Comparator group

Description:

The first administration of Cyclosporin A (CsA) was within the first 24 hours post-transplantation at an initial dose of 10-15mg/kg/day either orally, via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the study, the dose of CsA was adjusted, as necessary, to achieve and maintain the C2 or C0 blood CsA concentration within the target ranges. Before enrolling the first patient, each center chose the adjunct immunosuppressive (IS) regimen between: * Steroids administered and tapered as per local practice * interleukin-2 receptor (IL-2R) antagonists + mycophenolic acid (MPA): Induction with IL-2R antagonists; Dosages were as per center practice. Patients received mycophenolic acid (MPA) no later than 24 hours after reperfusion of the graft. Dosages were as per local practice. The regimen selected by the center was to be given to all patients enrolled in the trial from this center.

Treatment:

Drug: Cyclosporine A

Tacrolimus

Active Comparator group

Description:

Tacrolimus was administered within the first 24 hours post-transplantation at an initial dose of 0.1-0.15 mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally or via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout study period. Throughout the study, the dose of tacrolimus was adjusted as necessary to achieve and maintain C0 tacrolimus concentrations within target ranges. Before enrolling the first patient, each center chose adjunct immunosuppressive (IS) regimen between: * Steroids administered and tapered as per local practice * interleukin-2 receptor (IL-2R) antagonists + mycophenolic acid (MPA): Induction with IL-2R antagonists; Dosages were as per center practice. Patients received mycophenolic acid (MPA) no later than 24 hours after reperfusion of the graft. Dosages were as per local practice. The regimen selected by center was to be given to all patients enrolled in trial from this center.

Treatment:

Drug: Tacrolimus