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

NCT00260208 | Terminated Phase 4 Results

• 1 other identifier: COLO400A2426
• Study Type: interventional
• Target: 361
• Locations: 2 countries
• Sites: 2

Brief Summary

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

Conditions

Liver Transplant; Hepatitis C

Keywords

Liver transplant, adults, hepatitis C, liver fibrosis, cyclosporine microemulsion, tacrolimus

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Fibrosis Score 2 or Above [Ishak-Knodell Fibrosis Score (FS) ≥ 2] Within 1 Year Post-transplant

  Assessment of hepatic fibrosis was performed with liver biopsies at Day 1, Month 6, 12 and 24, read centrally by two independent pathologists blinded to treatment arm and time of biopsy. Ishak-Knodell score was used to stage liver disease; 0= None; 1= Portal fibrosis (some); 2= Portal fibrosis (most); 3= Bridging fibrosis (few); 4= Bridging fibrosis (many); 5 = Incomplete cirrhosis; 6 = Cirrhosis. Higher score indicates greater fibrosis. Logistic regression on the presence of IK\>=2 was applied based on central biopsy readings only.

  1 year post-transplant

Secondary Outcomes (11)

• Number of Participants With Combined Endpoint of Death or Graft Loss or Fibrosis Score (FS) ≥ 2

  1 year post-transplant

• Number of Participants With Fibrosing Cholestatic Hepatitis

  1 year post-transplantation

• Number of Participants With Death, Graft Loss, Death or Graft Loss, Graft Loss With Re-transplantation

  1 year post-transplant

• Number of Participants With Treated Acute Rejection, Biopsy Proven Acute Rejection (BPAR), and Sub-clinical Rejection

  1 year post-transplant

• Number of Participants With Combined Endpoint of Death or Graft Loss or Biopsy Proven Acute Rejection (BPAR)

  1 year post-transplant

Study Arms (2)

Cyclosporin A

ACTIVE COMPARATOR

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.

Drug: Cyclosporine A

Tacrolimus

ACTIVE COMPARATOR

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.

Drug: Tacrolimus

Interventions

Cyclosporine A DRUG

Initial dose of 10-15mg/kg/day either orally, via a nasogastric (NG) tube or intravenously (i.v.) within the first 24 hours post-transplantation.

Also known as: Neoral

Cyclosporin A

Tacrolimus DRUG

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 either orally or via a nasogastric (NG) tube or intravenously (i.v).

Tacrolimus

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (2)

Novartis Investigative Site

East Hanover, New Jersey, United States

Location

Novartis Investigational Site

Zurich, 8091, Switzerland

Location

MeSH Terms

Conditions

Hepatitis C; Liver Cirrhosis

Interventions

Cyclosporine; Tacrolimus

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Macrolides; Lactones; Organic Chemicals

Limitations and Caveats

This study was prematurely discontinued due to poor recruitment. Since only a small patient group could be analyzed for primary outcome measure, robust conclusions on the effect of the two calcineurin inhibitors on the fibrosis score cannot be drawn.

Results Point of Contact

• Title: Study coordinator
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2005
• First Posted: December 1, 2005
• Study Start: January 1, 2006
• Primary Completion: September 1, 2010
• Last Updated: December 6, 2011
• Results First Posted: October 26, 2011

Record last verified: 2011-12

Locations

CH (1); US (1)