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

End Stage Renal Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00172809
• Other study ID #: 940209
• Status: Completed
• Phase: Phase 4
• First received: September 12, 2005
• Last updated: March 5, 2008
• Start date: July 2005
• Est. completion date: January 2007

Study information

• Verified date: June 2007
• Source: National Taiwan University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Taiwan: Department of Health
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: January 2007
• Est. primary completion date: June 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis C
• End Stage Renal Disease
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic
• Kidney Diseases
• Kidney Failure, Chronic

Intervention

Drug:
• Peginterferon alfa-2a
Peginterferon alfa-2a 135 ug/week for 24 weeks
• Interferon alfa-2a
Interferon alfa-2a 3 MU tiw for 24 weeks

Locations

Country	Name	City	State
Taiwan	National Taiwan University Hospital, Yun-Lin Branch	Douliou

Sponsors (1)

Lead Sponsor	Collaborator
National Taiwan University Hospital

Country where clinical trial is conducted

Taiwan, 

References & Publications (12)

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. Erratum in: Nephrol Dial Transplant 1994;9(12):1850. — View Citation

Casanovas Taltavull T, Baliellas C, Sesé E, Iborra MJ, Benasco C, Andrés E, González 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. — View Citation

Casanovas-Taltavull T, Baliellas C, Benasco C, Serrano TT, Casanova A, Pérez JL, Guerrero L, González 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sustained histological response and sustained virological response 6 months after the completion of the intervention		1 year	Yes
Secondary	The overall tolerance of the two different regimens and the comparison of the rates of side effects		1 year	Yes