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
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
Detaillierte Beschreibung
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.
Studientyp
Einschreibung (Tatsächlich)
Phase
- Phase 4
Kontakte und Standorte
Studienorte
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Douliou, Taiwan
- National Taiwan University Hospital, Yun-Lin branch
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Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
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
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Zufällig
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
|---|---|
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Aktiver Komparator: 1
Peginterferon alfa-2a (Pegasys, Hoffmann-LaRoche) 135 ug/week for 24 weeks
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Peginterferon alfa-2a 135 ug/week for 24 weeks
Andere Namen:
|
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Aktiver Komparator: 2
Interferon alfa-2a (Roferon, Hoffmann-LaRoche) 3 MU tiw for 24 weeks
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Interferon alfa-2a 3 MU tiw for 24 weeks
Andere Namen:
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Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Zeitfenster |
|---|---|
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Sustained histological response and sustained virological response 6 months after the completion of the intervention
Zeitfenster: 1 year
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1 year
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Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Zeitfenster |
|---|---|
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The overall tolerance of the two different regimens and the comparison of the rates of side effects
Zeitfenster: 1 year
|
1 year
|
Mitarbeiter und Ermittler
Ermittler
- Hauptermittler: Chen-Hua Liu, M.D., Department of Internal Medicine, National Taiwan Univeristy Hospital, Yun-Lin Branch
Publikationen und hilfreiche Links
Allgemeine Veröffentlichungen
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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. doi: 10.1159/000188705.
- 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.
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn
Primärer Abschluss (Tatsächlich)
Studienabschluss (Tatsächlich)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Schätzen)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Schätzen)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Erkrankungen des Verdauungssystems
- RNA-Virusinfektionen
- Viruserkrankungen
- Infektionen
- Durch Blut übertragene Infektionen
- Übertragbare Krankheiten
- Urologische Erkrankungen
- Leberkrankheiten
- Niereninsuffizienz
- Flaviviridae-Infektionen
- Hepatitis, viral, menschlich
- Enterovirus-Infektionen
- Picornaviridae-Infektionen
- Niereninsuffizienz, chronisch
- Nierenerkrankungen
- Hepatitis
- Hepatitis A
- Hepatitis C
- Hepatitis, chronisch
- Nierenversagen, chronisch
- Hepatitis C, chronisch
- Physiologische Wirkungen von Arzneimitteln
- Antiinfektiva
- Antivirale Mittel
- Antineoplastische Mittel
- Immunologische Faktoren
- Interferone
- Interferon-alpha
- Peginterferon alfa-2a
- Interferon alpha-2
Andere Studien-ID-Nummern
- 940209
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