Interferon Treatment for Patients With Chronic Hepatitis C and End Stage Renal Disease

This study has been completed.
Sponsor:
Information provided by:
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT00172809
First received: September 12, 2005
Last updated: March 5, 2008
Last verified: June 2007

September 12, 2005
March 5, 2008
July 2005
June 2006   (final data collection date for primary outcome measure)
Sustained histological response and sustained virological response 6 months after the completion of the intervention [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
Sustained histological response and sustained virological response 6 months after the completion of the intervention
Complete list of historical versions of study NCT00172809 on ClinicalTrials.gov Archive Site
The overall tolerance of the two different regimens and the comparison of the rates of side effects [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
The overall tolerance of the two different regimens and the comparison of the rates of side effects
Not Provided
Not Provided
 
Interferon Treatment for Patients With Chronic Hepatitis C and End Stage Renal Disease
A Pilot Study in Comparing the Efficacy and Safety of Peginterferon Alfa-2a and Interferon Alfa-2a in Treating Patients With End Stage Renal Disease and Chronic Hepatitis C

The treatment response with conventional interferon alpha alone in patients with end stage renal disease and chronic hepatitis C is about 33-39%. However, the drop-out rate is 17-29.6%. Pegylated interferon alpha, a newly developed form of interferon with superior pharmacokinetic profiles, has not been used to treatment these patients. We expect the better treatment response treated with peginterferon alpha than conventional interferon. In addition, we also observe the safety of the two drugs during the study. The goal of the study is to compare the efficacy and safety of the two different treatment regimens in patients with chronic hepatitis C and end stage renal disease.

Chronic hepatitis C virus (HCV) infection is common among patients with end stage renal disease (ESRD), with the reported prevalence ranging from 8 to 20% in dialysis patients in developed world. In Taiwan, the estimated prevalence of HCV infection in patients with ESRD who maintain hemodialysis ranges from 20 to 24.7%. Although most studies have provided mild to moderate disease activity and a high proportion of normal alanine aminotransferase (ALT) levels, the frequency of bridging hepatic fibrosis or cirrhosis ranges from 5 to 32%. Several studies have shown that chronic hepatitis C adversely affects the survival in patients with ESRD. After renal transplantation, recipients with HCV have an increased risk of liver-related mortality and morbidity compared with those without HCV. Therefore, eradication of HCV can improve clinical outcome in dialysis patients as well as in patients awaiting renal transplantation.

Combined interferon and ribavirin is the standard therapy in HCV-infected patients with normal renal function. However, ribavirin, which is cleared by the kidneys, may cause severe hemolytic anemia and be dangerous in dialysis patients. Two recent meta-analyses showed that the sustained virological responses were (SVR) 39% and 33%; the drop-out rate were 17% and 29.6% in HCV-infected dialysis patients treated with interferon-alpha 3 MU thrice weekly of varied duration. The response and the drop-out rate were higher than that reported in HCV-infected patients with normal renal function (SVR of 7-16% by interferon-alpha 3 MU thrice weekly for 24 weeks; drop-out rate of 5-9%) due to a lower interferon clearance rate.

Peginterferon alpha-2a (40KD) is a modified form of interferon alpha-2a consisting of a branched polyethylene glycol (PEG) chain covalently bound to interferon alpha-2a. A better response of peginterferon alpha-2a than interferon alpha-2a has been demonstrated in HCV-infected patients with normal renal function, either combined with ribavirin or not, due to the superior pharmacokinetic profiles. The clearance of peginterferon alpha-2a for ESRD patients was about 30-40% lower than that in healthy subjects. A similarly pharmacokinetic profile of peginterferon alpha-2a is observed with 135 μg weekly in dialysis patients compared with 180μg weekly in patients with normal renal function.

We expect that peginterferon alpha-2a is superior to interferon alpha-2a in achieving an increased SVR and decreased drop-out rate in dialysis patients. The goal of the study is to compare the efficacy and safety of the two different treatment regimens in patients with chronic hepatitis C and end stage renal disease.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Chronic Hepatitis C
  • End Stage Renal Disease
  • Drug: Peginterferon alfa-2a
    Peginterferon alfa-2a 135 ug/week for 24 weeks
    Other Name: Pegasus 135 ug/syringe
  • Drug: Interferon alfa-2a
    Interferon alfa-2a 3 MU tiw for 24 weeks
    Other Name: Roferon 3 MU/syringe
  • Active Comparator: 1
    Peginterferon alfa-2a (Pegasys, Hoffmann-LaRoche) 135 ug/week for 24 weeks
    Intervention: Drug: Peginterferon alfa-2a
  • Active Comparator: 2
    Interferon alfa-2a (Roferon, Hoffmann-LaRoche) 3 MU tiw for 24 weeks
    Intervention: Drug: Interferon alfa-2a

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
50
January 2007
June 2006   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Age between 18 to 65 years old
  • Creatinine clearance (Ccr) < 10 ml/min/1.73 m2
  • Receiving regular hemodialysis
  • Anti-HCV (Abbott HCV EIA 2.0, Abbott Diagnostic, Chicago, IL) positive > 6 months
  • Detectable serum HCV-RNA (Cobas Amplicor HCV Monitor v2.0, Roche Molecular Systems, Pleasanton, CA) with dynamic range 600~<500,000 IU/ml

Exclusion Criteria:

  • Neutropenia (neutrophil count, <1,500/mm3)
  • Thrombocytopenia (platelet <90,000/ mm3)
  • Co-infection with HBV or HIV
  • Chronic alcohol abuse (daily consumption > 20 g/day)
  • Decompensated liver disease (Child classification B or C)
  • Neoplastic disease
  • An organ transplant
  • Immunosuppressive therapy
  • Poorly controlled autoimmune diseases, pulmonary diseases, cardiac diseases, psychiatric diseases, neurological diseases, diabetes mellitus
  • Evidence of drug abuse
  • Unwilling to have contraception
Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
Taiwan
 
NCT00172809
940209
Yes
National Taiwan University Hospital
National Taiwan University Hospital
Not Provided
Principal Investigator: Chen-Hua Liu, M.D. Department of Internal Medicine, National Taiwan Univeristy Hospital, Yun-Lin Branch
National Taiwan University Hospital
June 2007

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP