Retreatment of Dialysis Patients With Chronic Hepatitis C With Pegylated Interferon Alfa-2a Plus Low Dose Ribavirin

NCT00491179 | Completed Phase 4 Results DMC

• 1 other identifier: 200703032M
• Study Type: interventional
• Target: 35
• 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. 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%. Although dialysis patients have a higher SVR rate to conventional IFN or pegylated IFN monotherapy than patients with normal renal function for HCV therapy. More than half of these patients are relapsers or non-responders to IFN monotherapy. Retreatment of HCV-patients with normal renal function by combined pegylated IFN alfa plus ribavirin who fail to response to IFN monotherapy has achieved a SVR rate of 28%. Based on the long-term favorable outcome in dialysis patients who eradicate HCV, the aim of the study is to evaluate the efficacy and safety of retreatment by pegylated IFN alfa-2a plus low dose ribavirin in dialysis patients who fail to achieve HCV eradication by conventional or pegylated IFN alfa.

Conditions

Chronic Hepatitis C; Hemodialysis

Keywords

Chronic hepatitis C; hemodialysis; interferon; ribavirin

Outcome Measures

Primary Outcomes (1)

• 1.Number of Participants With Sustained Virologic Response (SVR) 2.Number of Participants Who Droppoed Out of the Study Prematurely Due to Adverse Events (AEs)

  1. Number of participants with sustained virologic response (SVR): number of patients with undetectable HCV RNA 6 months off therapy by real-time PCR test (Cobas TaqMan HCV Test v2.0, Roche Diagnostics GmbH, Mannheim, Germany, limit of detection \< 25 IU/mL) 2. Number of participants who droppoed out of the study prematurely due to adverse events (AEs): number of patients who prematurely withdrew from the study due to any adverse events

  1.5 year

Secondary Outcomes (1)

• Number of Participants With Histologic Response(HR)

  1.5 year

Study Arms (2)

Pegylated IFN + RBV for HCV genotype 1

EXPERIMENTAL

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

Drug: Pegylated interferon alfa-2a and ribavirin

Pegylated IFN + RBV for HCV genotype 2

EXPERIMENTAL

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

Drug: Pegylated interferon alfa-2a and ribavirin

Interventions

Pegylated interferon 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 48 weeks

Pegylated IFN + RBV for HCV genotype 1

Eligibility Criteria

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

You may qualify if:

• Non-responders or relapsers of dialysis patients to conventional interferon or pegylated interferon monotherapy
• 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 Monitor v2.0, Roche Diagnostics) with dynamic range 25- 391000000 IU/ml

You may not qualify if:

• 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 (29)

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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

Results Point of Contact

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

jacque_liu@mail2000.com.tw

886223123456

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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: June 23, 2007
• First Posted: June 26, 2007
• Study Start: June 1, 2006
• Primary Completion: June 1, 2008
• Study Completion: July 1, 2008
• Last Updated: November 13, 2009
• Results First Posted: November 13, 2009

Record last verified: 2009-10

Locations

TW (1)