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Pegylated Interferon Alfa-2a Plus Low Dose Ribavirin for Treatment-Naïve Dialysis Patients With Chronic Hepatitis C

Information source: National Taiwan University Hospital
Information obtained from ClinicalTrials.gov on February 07, 2013
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Chronic Hepatitis C

Intervention: Pegylated interferon alfa-2a and ribavirin (Drug); Pegylated interferon alfa-2a (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: National Taiwan University Hospital

Official(s) and/or principal investigator(s):
Chen-Hua Liu, MD, Study Chair, Affiliation: Department of Internal Medicine, National Taiwan Universitys Hospital

Overall contact:
Chen-Hua Liu, MD, Phone: 886-2-23123456, Ext: 3572, Email: jacque_liu@mail2000.com.tw

Summary

Chronic hepatitis C virus (HCV) infection is common in dialysis patients. Interferon (IFN)-based treatment for chronic hepatitis C has been the mainstay therapy in immunocompetent patients. In dialysis patients, treatment with conventional or pegylated interferon has also received much attention recently. Two meta-analyses evaluating the efficacy and safety of conventional IFN alfa monotherapy showed that the sustained virologic response (SVR) rates were 37% and 33%, respectively; and the corresponding dropout rates were 17% and 29. 6%, respectively. The efficacy and safety of pegylated IFN alfa-2a and 2b in treating dialysis patients showed conflicting results, with a more favorable outcome of patients treated with pegylated IFN alfa-2a (135-180 μg/week: SVR 33-75%, well tolerated) than those treated with pegylated IFN alfa-2b (0. 5-1. 0 μg/week: SVR 12. 5%, poorly tolerated. Currently, IFN-based therapy to treatment HCV infection should be initiated in dialysis stages, because the use of IFN in RT patients harbors high risks of acute graft rejection,and have low response rates under the concomitant use of immunosuppressive agents.

Ribavirin, which has been used in combination with IFN to treat chronic hepatitis C in the general patients and achieve a higher SVR rate than IFN monotherapy, is considered contraindicated in dialysis patients with chronic hepatitis C due to the risk of severe hemolytic anemia. However, some pilot studies evaluating combined conventional IFN alfa plus low dose ribavirin (170-300 mg/day) showed SVR rates of 17%-66% after 24-48 weeks of treatment. In addition, a recent study including 6 patients with combination of pegylated IFN alfa plus low dose ribavirin also showed a SVR rate of 50%. In this study, treatment with pegylated IFN alfa-2a plus low dose ribavirin achieved a higher SVR rate that that with pegylated IFN alfa-2b plus low dose ribavirin (100% vs. 25%).

Based on the long-term favorable outcome in dialysis patients who eradicate HCV, and the superior response of pegylated IFN alfa-2a plus low dose ribavirin to pegylated IFN alfa-2b plus low dose ribavirin in treating dialysis patients with chronic hepatitis C, the aim of the study is to evaluate the efficacy and safety of pegylated IFN alfa-2a plus low dose ribavirin versus pegylated interferon alfa-2a alone in treatment naïve dialysis patients with chronic hepatitis C.

Clinical Details

Official title: Pegylated Interferon Alfa-2a Plus Low Dose Ribavirin Versus Pegylated Interferon Alfa-2a Alone for Treatment-nave Dialysis Patients With Chronic Hepatitis C

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

Primary outcome: Sustained virologic response (SVR) Drop-out rate

Secondary outcome: Histologic response (HR) Biochemical response (BR)

Detailed description: Chronic hepatitis C virus (HCV) infection is common in dialysis patients, with the reported prevalence varying from 3% to 80% worldwide. (1-3) Although these patients usually have mild symptoms and moderate elevation of alanine transaminase levels, recent international collaborative survey and prospective studies found that anti-HCV seropositivity and positive HCV RNA were risk factors for mortality and hepatocellular carcinoma (HCC). (4-7) Furthermore, progressive hepatic fibrosis, poor patient and graft survival were observer in dialysis patients with HCV infection who undergo renal transplantation (RT), suggesting immunosuppression following RT may worsen the course of hepatic fibrosis and renal graft function. (8-13) These lines of evidence indicate that HCV infection in the dialysis population is an important issue to be tackled.

Interferon (IFN)-based treatment for chronic hepatitis C has been the mainstay therapy in immunocompetent patients. In dialysis patients, treatment with conventional or pegylated interferon has also received much attention recently. Two meta-analyses evaluating the efficacy and safety of conventional IFN alfa monotherapy showed that the sustained virologic response (SVR) rates were 37% and 33%, respectively; and the corresponding dropout rates were 17% and 29. 6%, respectively.(14,15) The efficacy and safety of pegylated IFN alfa-2a and 2b in treating dialysis patients showed conflicting results, with a more favorable outcome of patients treated with pegylated IFN alfa-2a (135-180 μg/week: SVR 33-75%, well tolerated) than those treated with pegylated IFN alfa-2b (0. 5-1. 0 μg/week: SVR 12. 5%, poorly tolerated), (16-21) which may result from different pharmacokinetic profiles between these two pegylated IFNs. Currently, IFN-based therapy to treatment HCV infection should be initiated in dialysis stages, because the use of IFN in RT patients harbors high risks of acute graft rejection,(22,23) and have low response rates under the concomitant use of immunosuppressive agents. (24,25) Ribavirin, which has been used in combination with IFN to treat chronic hepatitis C in the general patients and achieve a higher SVR rate than IFN monotherapy, is considered contraindicated in dialysis patients with chronic hepatitis C due to the risk of severe hemolytic anemia. However, some pilot studies evaluating combined conventional IFN alfa plus low dose ribavirin (170-300 mg/day) showed SVR rates of 17%-66% after 24-48 weeks of treatment. (26-28) In addition, a recent study including 6 patients with combination of pegylated IFN alfa plus low dose ribavirin also showed a SVR rate of 50%. (29) In this study, treatment with pegylated IFN alfa-2a plus low dose ribavirin achieved a higher SVR rate that that with pegylated IFN alfa-2b plus low dose ribavirin (100% vs. 25%) Based on the long-term favorable outcome in dialysis patients who eradicate HCV, and the superior response of pegylated IFN alfa-2a plus low dose ribavirin to pegylated IFN alfa-2b plus low dose ribavirin in treating dialysis patients with chronic hepatitis C, the aim of the study is to evaluate the efficacy and safety of pegylated IFN alfa-2a plus low dose ribavirin versus pegylated interferon alfa-2a in treatment naïve dialysis patients with chronic hepatitis C.

Eligibility

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Age 18-65 years old

- Creatinine clearance (Ccr) < 10 ml/min/1. 73 m2

- Anti-HCV (Abbott HCV EIA 2. 0, Abbott Diagnostic, Chicago, IL) positive > 6 months

- Detectable serum quantitative HCV-RNA (Cobas Taqman HCV test, version 2, Roche

Diagnostics) with a dynamic range of 25-391000000 IU/ml

Exclusion Criteria:

- Receiving interferon-based therapy for chronic hepatitis C

- Severe anemia (hemoglobin < 10 g/dL) or hemoglobinopathy

- 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)

- Autoimmune liver disease

- 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

Locations and Contacts

Chen-Hua Liu, MD, Phone: 886-2-23123456, Ext: 3572, Email: jacque_liu@mail2000.com.tw

National Taiwan University Hospital, Taipei 100, Taiwan; Recruiting
Additional Information

Related publications:

Fabrizi F, Poordad FF, Martin P. Hepatitis C infection and the patient with end-stage renal disease. Hepatology. 2002 Jul;36(1):3-10. Review.

Kao JH, Huang CH, Chen W, Tsai TJ, Lee SH, Hung KY, Chen DS. GB virus C infection in hemodialysis patients: molecular evidence for nosocomial transmission. J Infect Dis. 1999 Jul;180(1):191-4.

Hou CH, Chen WY, Kao JH, Chen DS, Yang Y, Chen JJ, Lee SH, Wu DJ, Yang SC. Intrafamilial transmission of hepatitis C virus in hemodialysis patients. J Med Virol. 1995 Apr;45(4):381-5.

Maisonneuve P, Agodoa L, Gellert R, Stewart JH, Buccianti G, Lowenfels AB, Wolfe RA, Jones E, Disney AP, Briggs D, McCredie M, Boyle P. Cancer in patients on dialysis for end-stage renal disease: an international collaborative study. Lancet. 1999 Jul 10;354(9173):93-9.

Nakayama E, Akiba T, Marumo F, Sato C. Prognosis of anti-hepatitis C virus antibody-positive patients on regular hemodialysis therapy. J Am Soc Nephrol. 2000 Oct;11(10):1896-902.

Stehman-Breen CO, Emerson S, Gretch D, Johnson RJ. Risk of death among chronic dialysis patients infected with hepatitis C virus. Am J Kidney Dis. 1998 Oct;32(4):629-34.

Pereira BJ, Natov SN, Bouthot BA, Murthy BV, Ruthazer R, Schmid CH, Levey AS. Effects of hepatitis C infection and renal transplantation on survival in end-stage renal disease. The New England Organ Bank Hepatitis C Study Group. Kidney Int. 1998 May;53(5):1374-81.

Mathurin P, Mouquet C, Poynard T, Sylla C, Benalia H, Fretz C, Thibault V, Cadranel JF, Bernard B, Opolon P, Coriat P, Bitker MO. Impact of hepatitis B and C virus on kidney transplantation outcome. Hepatology. 1999 Jan;29(1):257-63.

Legendre C, Garrigue V, Le Bihan C, Mamzer-Bruneel MF, Chaix ML, Landais P, Kreis H, Pol S. Harmful long-term impact of hepatitis C virus infection in kidney transplant recipients. Transplantation. 1998 Mar 15;65(5):667-70.

Vosnides GG. Hepatitis C in renal transplantation. Kidney Int. 1997 Sep;52(3):843-61. No abstract available.

Izopet J, Rostaing L, Sandres K, Cisterne JM, Pasquier C, Rumeau JL, Duffaut M, Durand D, Puel J. Longitudinal analysis of hepatitis C virus replication and liver fibrosis progression in renal transplant recipients. J Infect Dis. 2000 Mar;181(3):852-8.

Zylberberg H, Nalpas B, Carnot F, Skhiri H, Fontaine H, Legendre C, Kreis H, Brechot C, Pol S. Severe evolution of chronic hepatitis C in renal transplantation: a case control study. Nephrol Dial Transplant. 2002 Jan;17(1):129-33.

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.

Kokoglu OF, Ucmak H, Hosoglu S, Cetinkaya A, Kantarceken B, Buyukbese MA, Isik IO. Efficacy and tolerability of pegylated-interferon alpha-2a in hemodialysis patients with chronic hepatitis C. J Gastroenterol Hepatol. 2006 Mar;21(3):575-80.

Sporea I, Popescu A, Sirli R, Golea O, Totolici C, Danila M, Vernic C. Pegylated-interferon alpha 2a treatment for chronic hepatitis C in patients on chronic haemodialysis. World J Gastroenterol. 2006 Jul 14;12(26):4191-4.

Chan TM, Ho SK, Tang CS, Tse KC, Lam MF, Lai KN, Yung S. Pilot study of pegylated interferon-alpha 2a in dialysis patients with chronic hepatitis C virus infection. Nephrology (Carlton). 2007 Feb;12(1):11-7.

Russo MW, Ghalib R, Sigal S, Joshi V. Randomized trial of pegylated interferon alpha-2b monotherapy in haemodialysis patients with chronic hepatitis C. Nephrol Dial Transplant. 2006 Feb;21(2):437-43. Epub 2005 Oct 18.

Annicchiarico BE, Siciliano M. Pegylated interferon-alpha 2b monotherapy for haemodialysis patients with chronic hepatitis C. Aliment Pharmacol Ther. 2004 Jul 1;20(1):123-4; author reply 124. No abstract available.

Potthoff A, Wiegand J, Luth JB, Wedemeyer H, Manns MP, Tillmann HL. Superiority of standard interferon-alpha2b compared to pegylated interferon-alpha2b (12 kDa) in a hemodialysis patient with chronic hepatitis C? Clin Nephrol. 2005 Mar;63(3):232-5.

Magnone M, Holley JL, Shapiro R, Scantlebury V, McCauley J, Jordan M, Vivas C, Starzl T, Johnson JP. Interferon-alpha-induced acute renal allograft rejection. Transplantation. 1995 Apr 15;59(7):1068-70. No abstract available.

Morales JM. Hepatitis C virus infection and renal disease after renal transplantation. Transplant Proc. 2004 Apr;36(3):760-2. Review.

Rostaing L, Izopet J, Baron E, Duffaut M, Puel J, Durand D. Treatment of chronic hepatitis C with recombinant alpha 2b interferon in kidney transplant recipients: preliminary results and side effects. Transplant Proc. 1995 Feb;27(1):948-50. No abstract available.

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.

Mousa DH, Abdalla AH, Al-Shoail G, Al-Sulaiman MH, Al-Hawas FA, Al-Khader AA. Alpha-interferon with ribavirin in the treatment of hemodialysis patients with hepatitis C. Transplant Proc. 2004 Jul-Aug;36(6):1831-4.

Bruchfeld A, Stahle L, Andersson J, Schvarcz R. Ribavirin treatment in dialysis patients with chronic hepatitis C virus infection--a pilot study. J Viral Hepat. 2001 Jul;8(4):287-92.

Bruchfeld A, Stahle L, Andersson J, Schvarcz R. Interferon and ribavirin therapy in dialysis patients with chronic hepatitis C. Nephrol Dial Transplant. 2001 Aug;16(8):1729. No abstract available.

Bruchfeld A, Lindahl K, Reichard O, Carlsson T, Schvarcz R. Pegylated interferon and ribavirin treatment for hepatitis C in haemodialysis patients. J Viral Hepat. 2006 May;13(5):316-21.

Starting date: June 2006
Last updated: December 18, 2012

Page last updated: February 07, 2013

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