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

NCT ID: NCT00172809

Last Updated: 2008-03-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-07-31

Study Completion Date

2007-01-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Chronic Hepatitis C End Stage Renal Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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1

Peginterferon alfa-2a (Pegasys, Hoffmann-LaRoche) 135 ug/week for 24 weeks

Group Type ACTIVE_COMPARATOR

Peginterferon alfa-2a

Intervention Type DRUG

Peginterferon alfa-2a 135 ug/week for 24 weeks

2

Interferon alfa-2a (Roferon, Hoffmann-LaRoche) 3 MU tiw for 24 weeks

Group Type ACTIVE_COMPARATOR

Interferon alfa-2a

Intervention Type DRUG

Interferon alfa-2a 3 MU tiw for 24 weeks

Interventions

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Peginterferon alfa-2a

Peginterferon alfa-2a 135 ug/week for 24 weeks

Intervention Type DRUG

Interferon alfa-2a

Interferon alfa-2a 3 MU tiw for 24 weeks

Intervention Type DRUG

Other Intervention Names

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Pegasus 135 ug/syringe Roferon 3 MU/syringe

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Taiwan University Hospital

OTHER

Sponsor Role lead

Responsible Party

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National Taiwan University Hospital

Principal Investigators

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Chen-Hua Liu, M.D.

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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National Taiwan University Hospital, Yun-Lin Branch

Douliu, , Taiwan

Site Status

Countries

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Taiwan

References

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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. doi: 10.1046/j.1365-2036.2003.01780.x.

Reference Type BACKGROUND
PMID: 14653826 (View on PubMed)

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. doi: 10.1111/j.1572-0241.2003.07526.x.

Reference Type BACKGROUND
PMID: 12873587 (View on PubMed)

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. doi: 10.1159/000046646.

Reference Type BACKGROUND
PMID: 11799259 (View on PubMed)

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. doi: 10.1111/j.1572-0241.2001.03697.x.

Reference Type BACKGROUND
PMID: 11316166 (View on PubMed)

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. doi: 10.1016/s0041-1345(99)00603-x. No abstract available.

Reference Type BACKGROUND
PMID: 10578327 (View on PubMed)

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. doi: 10.1016/s0272-6386(99)70108-3.

Reference Type BACKGROUND
PMID: 10401016 (View on PubMed)

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. doi: 10.1159/000045035. No abstract available.

Reference Type BACKGROUND
PMID: 9647511 (View on PubMed)

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. doi: 10.1093/oxfordjournals.ndt.a027441. No abstract available.

Reference Type BACKGROUND
PMID: 8671933 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8592590 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7652784 (View on PubMed)

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. doi: 10.1159/000188705.

Reference Type BACKGROUND
PMID: 8569947 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7816309 (View on PubMed)

Prabhu AR, Rao IR, Nagaraju SP, Rajwar E, Venkatesh BT, Nair N S, Pai G, Reddy NP, Suvarna D. Interventions for dialysis patients with hepatitis C virus (HCV) infection. Cochrane Database Syst Rev. 2023 Apr 25;4(4):CD007003. doi: 10.1002/14651858.CD007003.pub3.

Reference Type DERIVED
PMID: 37096802 (View on PubMed)

Other Identifiers

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940209

Identifier Type: -

Identifier Source: org_study_id

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