Interferon Treatment for Patients With Chronic Hepatitis C and End Stage Renal Disease - Full Text View

Purpose

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.

Condition	Intervention	Phase
Chronic Hepatitis C End Stage Renal Disease	Drug: Peginterferon alfa-2a Drug: Interferon alfa-2a	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis C Kidney Failure

Drug Information available for: Interferon Interferon Alfa-2a Peginterferon Alfa-2a Hepatitis A Vaccines

U.S. FDA Resources

Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures:

Sustained histological response and sustained virological response 6 months after the completion of the intervention [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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 ]

Enrollment:	50
Study Start Date:	July 2005
Study Completion Date:	January 2007
Primary Completion Date:	June 2006 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 Peginterferon alfa-2a (Pegasys, Hoffmann-LaRoche) 135 ug/week for 24 weeks	Drug: Peginterferon alfa-2a Peginterferon alfa-2a 135 ug/week for 24 weeks Other Name: Pegasus 135 ug/syringe
Active Comparator: 2 Interferon alfa-2a (Roferon, Hoffmann-LaRoche) 3 MU tiw for 24 weeks	Drug: Interferon alfa-2a Interferon alfa-2a 3 MU tiw for 24 weeks Other Name: Roferon 3 MU/syringe

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00172809

Locations

Taiwan
National Taiwan University Hospital, Yun-Lin Branch
Douliou, Taiwan

Sponsors and Collaborators

National Taiwan University Hospital

Investigators

Principal Investigator:

Chen-Hua Liu, M.D.

Department of Internal Medicine, National Taiwan Univeristy Hospital, Yun-Lin Branch

More Information

Publications:

Fabrizi F, Dulai G, Dixit V, Bunnapradist S, Martin P. Meta-analysis: interferon for the treatment of chronic hepatitis C in dialysis patients. Aliment Pharmacol Ther. 2003 Dec;18(11-12):1071-81. Review.

Russo MW, Goldsweig CD, Jacobson IM, Brown RS Jr. Interferon monotherapy for dialysis patients with chronic hepatitis C: an analysis of the literature on efficacy and safety. Am J Gastroenterol. 2003 Jul;98(7):1610-5. Review.

Huraib S, Iqbal A, Tanimu D, Abdullah A. Sustained virological and histological response with pretransplant interferon therapy in renal transplant patients with chronic viral hepatitis C. Am J Nephrol. 2001 Nov-Dec;21(6):435-40.

Casanovas-Taltavull T, Baliellas C, Benasco C, Serrano TT, Casanova A, Perez JL, Guerrero L, Gonzalez MT, Andres E, Gil-Vernet S, Casais LA. Efficacy of interferon for chronic hepatitis C virus-related hepatitis in kidney transplant candidates on hemodialysis: results after transplantation. Am J Gastroenterol. 2001 Apr;96(4):1170-7.

Tokumoto T, Tanabe K, Ishikawa N, Simizu T, Oshima T, Noguchi S, Gouya N, Nakazawa H, Hashimoto E, Fuchinoue S, Hayashi N, Toma H. Effect of interferon-alpha treatment in hemodialysis patients and renal transplant recipients with chronic hepatitis C. Transplant Proc. 1999 Nov;31(7):2887-9. No abstract available.

Huraib S, Tanimu D, Romeh SA, Quadri K, Al Ghamdi G, Iqbal A, Abdulla A. Interferon-alpha in chronic hepatitis C infection in dialysis patients. Am J Kidney Dis. 1999 Jul;34(1):55-60.

Djordjevic V, Kostic S, Stefanovic V. Treatment of chronic hepatitis C with interferon alpha in patients on maintenance hemodialysis. Nephron. 1998;79(2):229-31. No abstract available.

Simsek H. Interferon-alpha treatment of haemodialysis patients with chronic viral hepatitis and its impact on kidney transplantation. Nephrol Dial Transplant. 1996 May;11(5):912-3. No abstract available.

Raptopoulou-Gigi M, Spaia S, Garifallos A, Xenou P, Orphanou H, Zarafidou E, Petridou P, Vrettou H, Vagionas G, Galaktidou G, et al. Interferon-alpha 2b treatment of chronic hepatitis C in haemodialysis patients. Nephrol Dial Transplant. 1995 Oct;10(10):1834-7.

Casanovas Taltavull T, Baliellas C, Sese E, Iborra MJ, Benasco C, Andres E, Gonzalez MT, Gil-Vernet S, Casanova A, Casais LA. Interferon may be useful in hemodialysis patients with hepatitis C virus chronic infection who are candidates for kidney transplant. Transplant Proc. 1995 Aug;27(4):2229-30. No abstract available.

Ozyilkan E, Simsek H, Uzunalimoglu B, Telatar H. Interferon treatment of chronic active hepatitis C in patients with end-stage chronic renal failure. Nephron. 1995;71(2):156-9.

Barril G, Schez Tomero JA, Garcia Buey L, Motellon JL, Bernis C, Traver JA. Response to alpha 2B interferon (IFN) treatment in a haemodialysis patient with chronic hepatitis C. Nephrol Dial Transplant. 1994;9(9):1354-5. No abstract available. Erratum in: Nephrol Dial Transplant 1994;9(12):1850.

Responsible Party:	National Taiwan University Hospital
ClinicalTrials.gov Identifier:	NCT00172809 History of Changes
Other Study ID Numbers:	940209
Study First Received:	September 12, 2005
Last Updated:	March 5, 2008
Health Authority:	Taiwan: Department of Health

Keywords provided by National Taiwan University Hospital:

Chronic Hepatitis C
End stage renal disease
Hemodialysis
Interferon
Pegylated interferon

Additional relevant MeSH terms:

Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Kidney Diseases
Kidney Failure, Chronic
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections

Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Interferon-alpha
Interferon Alfa-2a
Interferons
Peginterferon alfa-2a
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents

ClinicalTrials.gov processed this record on May 23, 2013