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

NCT00491244 | Completed Phase 4 Results DMC

• 1 other identifier: 200703010M
• Study Type: interventional
• Target: 377
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Chronic Hepatitis C

Keywords

Chronic hepatitis C; Hemodialysis; Interferon; Ribavirin

Outcome Measures

Primary Outcomes (1)

• Sustained Virologic Response (SVR)Rate

  1.5 year

Secondary Outcomes (1)

• Adverse Event (AE)-Related Withdrawal Rate

  1.5 year

Study Arms (2)

Peginterferon alfa-2a and ribavirin

EXPERIMENTAL

Pegylated interferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 135 ug/week plus ribavirin (Copegus, F. Hoffman-LaRoche) 200 mg/day for 24 to 48 weeks (genotype 1: 48 weeks, genotype 2: 24 weeks)

Drug: Peginterferon alfa-2a and ribavirin

Peginterferon alfa-2a

EXPERIMENTAL

Pegylated interferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 135 ug/week for 24 to 48 weeks (genotype 1: 48 weeks, genotype 2: 24 weeks)

Drug: Peginterferon alfa-2a

Interventions

Peginterferon alfa-2a and ribavirin DRUG

Pegylated interferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 135 ug/week plus ribavirin (Copegus, F. Hoffman-LaRoche) 200 mg/day for 24 to 48 weeks (genotype 1: 48 weeks, genotype 2: 24 weeks)

Also known as: Pegylated interferon alfa-2a (Pegasys, F. Hoffman-LaRoche), Ribavirin (Copegus, F. Hoffman-LaRoche)

Peginterferon alfa-2a and ribavirin

Peginterferon alfa-2a DRUG

Pegylated interferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 135 ug/week for 24 to 48 weeks (genotype 1: 48 weeks, genotype 2: 24 weeks)

Also known as: Pegylated interferon alfa-2a (Pegasys, F. Hoffman-LaRoche)

Peginterferon alfa-2a

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-65 years old
• Creatinine clearance (Ccr) \< 15 ml/min/1.73 m2
• Anti-HCV (Abbott HCV EIA 3.0, 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Taiwan University Hospital: lead
• National Science and Technology Council, Taiwan: collaborator
• Department of Health, Executive Yuan, R.O.C. (Taiwan): collaborator

Study Sites (1)

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Related Publications (31)

• Fabrizi F, Poordad FF, Martin P. Hepatitis C infection and the patient with end-stage renal disease. Hepatology. 2002 Jul;36(1):3-10. doi: 10.1053/jhep.2002.34613.

  PMID: 12085342 BACKGROUND

• 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. doi: 10.1086/314850.

  PMID: 10353878 BACKGROUND

• 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. doi: 10.1002/jmv.1890450405.

  PMID: 7545208 BACKGROUND

• 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. doi: 10.1016/s0140-6736(99)06154-1.

  PMID: 10408483 BACKGROUND

• 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):1896-1902. doi: 10.1681/ASN.V11101896.

  PMID: 11004221 BACKGROUND

• 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. doi: 10.1016/s0272-6386(98)70027-7.

  PMID: 9774125 BACKGROUND

• 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. doi: 10.1046/j.1523-1755.1998.00883.x.

  PMID: 9573555 BACKGROUND

• 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. doi: 10.1002/hep.510290123.

  PMID: 9862875 BACKGROUND

• 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. doi: 10.1097/00007890-199803150-00011.

  PMID: 9521201 BACKGROUND

• Vosnides GG. Hepatitis C in renal transplantation. Kidney Int. 1997 Sep;52(3):843-61. doi: 10.1038/ki.1997.403. No abstract available.

  PMID: 9291208 BACKGROUND

• 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. doi: 10.1086/315355.

  PMID: 10720504 BACKGROUND

• 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. doi: 10.1093/ndt/17.1.129.

  PMID: 11773476 BACKGROUND

• 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.

  PMID: 14653826 BACKGROUND

• 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.

  PMID: 12873587 BACKGROUND

• 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. doi: 10.1111/j.1440-1746.2005.04008.x.

  PMID: 16638102 BACKGROUND

• 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. doi: 10.3748/wjg.v12.i26.4191.

  PMID: 16830372 BACKGROUND

• 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. doi: 10.1111/j.1440-1797.2006.00662.x.

  PMID: 17295655 BACKGROUND

• 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. doi: 10.1093/ndt/gfi231. Epub 2005 Oct 18.

  PMID: 16234288 BACKGROUND

• 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. doi: 10.1111/j.1365-2036.2004.01954.x. No abstract available.

  PMID: 15225179 BACKGROUND

• 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. doi: 10.5414/cnp63232.

  PMID: 15786827 BACKGROUND

• 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. doi: 10.1097/00007890-199504150-00030. No abstract available.

  PMID: 7709447 BACKGROUND

• Morales JM. Hepatitis C virus infection and renal disease after renal transplantation. Transplant Proc. 2004 Apr;36(3):760-2. doi: 10.1016/j.transproceed.2004.03.041.

  PMID: 15110654 BACKGROUND

• 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.

  PMID: 7879242 BACKGROUND

• 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.

  PMID: 11316166 BACKGROUND

• 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. doi: 10.1016/j.transproceed.2004.07.025.

  PMID: 15350490 BACKGROUND

• 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. doi: 10.1046/j.1365-2893.2001.00300.x.

  PMID: 11454181 BACKGROUND

• 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. doi: 10.1093/ndt/16.8.1729. No abstract available.

  PMID: 11477195 BACKGROUND

• 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. doi: 10.1111/j.1365-2893.2005.00680.x.

  PMID: 16637862 BACKGROUND

• 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.

  PMID: 37096802 DERIVED

• Liu CH, Liu CJ, Huang CF, Lin JW, Dai CY, Liang CC, Huang JF, Hung PH, Tsai HB, Tsai MK, Lee CY, Chen SI, Yang SS, Su TH, Yang HC, Chen PJ, Chen DS, Chuang WL, Yu ML, Kao JH. Peginterferon alfa-2a with or without low-dose ribavirin for treatment-naive patients with hepatitis C virus genotype 2 receiving haemodialysis: a randomised trial. Gut. 2015 Feb;64(2):303-11. doi: 10.1136/gutjnl-2014-307080. Epub 2014 Apr 19.

  PMID: 24747867 DERIVED

• Liu CH, Huang CF, Liu CJ, Dai CY, Liang CC, Huang JF, Hung PH, Tsai HB, Tsai MK, Chen SI, Lin JW, Yang SS, Su TH, Yang HC, Chen PJ, Chen DS, Chuang WL, Yu ML, Kao JH. Pegylated interferon-alpha2a with or without low-dose ribavirin for treatment-naive patients with hepatitis C virus genotype 1 receiving hemodialysis: a randomized trial. Ann Intern Med. 2013 Dec 3;159(11):729-38. doi: 10.7326/0003-4819-159-11-201312030-00005.

  PMID: 24297189 DERIVED

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

peginterferon alfa-2a; Ribavirin

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

1. Open-label trial 2. Results may not be generalizable to peritoneal dialysis patients 3. Higher percentages of favorable IL28B genotypes 4. Secondary endpoint may not be powered to detect the differences

Results Point of Contact

• Title: Dr. Chen-Hua Liu
• Organization: National Taiwan University Hospital

jacque_liu@mail2000.com.tw

+886-2-23123456

Study Officials

• Chen-Hua Liu, MD

  Department of Internal Medicine, National Taiwan Universitys Hospital

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2007
• First Posted: June 26, 2007
• Study Start: June 1, 2007
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: February 10, 2014
• Results First Posted: December 13, 2013

Record last verified: 2014-01

Locations

TW (1)