Randomized Trial of 24 or 48 Weeks of Peginterferon Alfa-2a Plus Ribavirin for HCV Genotype 1-infected Patients

This study has been completed.
Sponsor:
Collaborator:
National Science Council, Taiwan
Information provided by:
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT00495131
First received: June 29, 2007
Last updated: September 7, 2009
Last verified: September 2009
  Purpose

Chronic hepatitis C virus (HCV) infection is prevalent in the world, affecting 3% of the world's population. The current standard of therapy is pegylated interferon and ribavirin, reaching 54-63% of successful rates. In patients with HCV genotype 1 infection, a 48 week course of combination therapy has achieved a higher successful rate that a 24 weeks course of therapy. However, several studies in Taiwan have shown that a 24 week course of therapy has comparable or even better response to a 48 week course of therapy in Western countries. Therefore, whether a 48 week course of therapy can achieve a higher response to a 24 week course of therapy in Taiwanese patients with genotype 1 HCV infection remains unclear.


Condition Intervention Phase
Hepatitis C, Chronic
Drug: Pegylated interferon alfa-2a plus ribavirin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Trial of 24 or 48 Weeks of Peginterferon Alfa-2a Plus Ribavirin for Chronic Hepatitis C Virus Genotype 1-infected Patients in Taiwan

Resource links provided by NLM:


Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures:
  • Sustained Virologic Response [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Sustained Biochemical Response [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Treatment-related Withdrawal Rate [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
  • Histologic Response [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Enrollment: 308
Study Start Date: June 2006
Study Completion Date: July 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Peginterfron and ribavirin (24 weeks)
Pegylated interferon alfa-2a (Pegasys, F. Hoffmann-LaRoche) 180 ug/week plus ribavirin (Robatrol, F. Hoffmann-LaRoche) 1000-1200 mg/day (<75 kg, 1000 mg/day; >= 75 kg, 1200 mg/day) for 24 weeks
Drug: Pegylated interferon alfa-2a plus ribavirin
Pegylated interferon alfa-2a (Pegasys, F. Hoffmann-LaRoche) 180 ug/week plus ribavirin (Robatrol, F. Hoffmann-LaRoche) 1000-1200 mg/day (<75 kg, 1000 mg/day; >= 75 kg, 1200 mg/day) for 24 weeks
Other Name: Pegasys plus Robatrol
Active Comparator: Peginterferon and ribavirin (48 weeks)
Pegylated interferon alfa-2a (Pegasys, F. Hoffmann-LaRoche) 180 ug/week plus ribavirin (Robatrol, F. Hoffmann-LaRoche) 1000-1200 mg/day (<75 kg, 1000 mg/day; >= 75 kg, 1200 mg/day) for 48 weeks
Drug: Pegylated interferon alfa-2a plus ribavirin
Pegylated interferon alfa-2a (Pegasys, F. Hoffmann-LaRoche) 180 ug/week plus ribavirin (Robatrol, F. Hoffmann-LaRoche) 1000-1200 mg/day (<75 kg, 1000 mg/day; >= 75 kg, 1200 mg/day) for 48 weeks
Other Name: Pegasys plus Robatrol

Detailed Description:

Combination therapy with interferon alfa (IFN-α) plus ribavirin for 24 to 48 weeks produces sustained virologic response (SVR) rate in approximately 31-47% of treatment naïve patients with chronic hepatitis C.(1-5) Patients with genotype 1 virus infection are less likely to have SVR that those with other genotypes infection, and therefore, patients infected with hepatitis C virus (HCV) genotype 1 should receive treatment for 48 weeks.(6) Recently, combination therapy with pegylated interferon alfa (pegylated IFN-α) plus ribavirin produces higher SVR rates (54-56%) than that with IFN-α plus ribavirin.(7,8) Furthermore, a large trial assessing the effect and duration of pegylated IFN-α plus ribavirin showed that the overall SVR rate was 63%. Among patients with genotype 1 HCV infection, standard dose ribavirin (1000 to 1200 mg per day) and 48 weeks of treatment were significantly more effective than low dose ribavirin (800 mg per day) or 24 weeks of treatment.(9) The SVR rate was 51% for genotype 1 patients receiving pegylated IFN-α plus standard dose ribavirin for 48 weeks, whereas only 29% and 41% for those receiving pegylated IFN-α plus low dose ribavirin and standard dose ribavirin for 24 weeks, respectively. Based on these lines of evidence, 48 weeks of therapy with pegylated IFN-α (pegylated IFN-α 2a 180 μg or pegylated IFN-α 2b 1.5 μg per kilogram body weight weekly) plus ribavirin (1000 to 1200 mg per day) is recommended to treat patients with HCV genotype 1 infection.(10) In Taiwan, a multicenter study showed that a 6 month course treatment with pegylated IFN-α plus standard dose ribavirin had a comparable SVR rate to that with IFN-α plus standard dose ribavirin (67.1% versus 63.6%) in patients with chronic hepatitis C. Subgroup analysis showed that treatment with pegylated IFN-α plus standard dose ribavirin had a significantly higher SVR rate to that with IFN-α plus standard dose ribavirin (65.8% versus 41.0%) in patients with genotype 1 HCV infection.(11) Recently, a pilot study comparing 24 and 48 weeks of pegylated IFN-α plus standard dose ribavirin in patients with genotype 1 HCV infection showed that 48 weeks of treatment is more efficacious that 24 weeks of treatment (SVR rate: 80.0% versus 48.9%).(12) However, much difference of SVR rates occurred in these two studies, making optimal therapy in Taiwanese patients infected with genotype 1 HCV difficult to be determined. In the study, we aim to investigate in a large cohort whether 48 weeks treatment with pegylated IFN-α plus standard dose ribavirin is more efficacious than 24 weeks treatment in patients with genotype 1 HCV infection.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Treatment naïve
  • Age 18 and older than 18 years old
  • Anti-HCV (Abbott HCV EIA 2.0, Abbott Diagnostic, Chicago, IL) positive > 6 months
  • Detectable serum quantitative HCV-RNA (Cobas Amplicor HCV Monitor v2.0, Roche Molecular Systems, Pleasanton, CA) with dynamic range 600~<500,000 IU/ml
  • HCV genotype 1 (Inno-LiPA HCV II, Innogenetics, Ghent, Belgium)
  • Serum alanine aminotransferase levels above the upper limit of normal with 6 months of enrollment
  • A liver biopsy consistent with the diagnosis of chronic hepatitis C

Exclusion Criteria:

  • Anemia (hemoglobin < 13 gram per deciliter for men and < 12 gram per deciliter for women)
  • Neutropenia (neutrophil count <1,500 per cubic milliliter)
  • Thrombocytopenia (platelet <90,000 per cubic milliliter)
  • Co-infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)
  • Chronic alcohol abuse (daily consumption > 20 gram per day)
  • Decompensated liver disease (Child-Pugh class B or C)
  • Serum creatinine level more than 1.5 times the upper limit of normal
  • Autoimmune liver disease
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00495131

Locations
Taiwan
National Taiwan University Hospital, Yun-Lin Branch
Douliou, Taiwan
Taichung Veterans General Hospital
Taichung, Taiwan
Far Eastern Memorial Hospital
Taipei, Taiwan
Ren-Ai Branch, Taipei Municipal Hospital
Taipei, Taiwan
Buddhist Tzu Chi General Hospital
Taipei, Taiwan
National Taiwan University Hospital
Taipei, Taiwan, 100
Sponsors and Collaborators
National Taiwan University Hospital
National Science Council, Taiwan
Investigators
Study Chair: Jia-Horng Kao, MD, PhD National Taiwan University Hospital
Study Director: Ding-Shinn Chen, MD National Taiwan University Hospital
Study Director: Ming-Yang Lai, MD, PhD National Taiwan University Hospital
Study Director: Pei-Jer Chen, MD, PhD National Taiwan University Hospital
Principal Investigator: Chun-Jen Liu, MD, PhD National Taiwan University Hospital
Principal Investigator: Chen-Hua Liu, MD National Taiwan University Hospital
Principal Investigator: Shih-Jer Hsu, MD National Taiwan University Hosptial, Yun-Lin Branch
Principal Investigator: Chih-Lin Lin, MD Ren-Ai Branch, Taipei City Hospital
Principal Investigator: Cheng-Chao Liang, MD Far Eastern Memorial Hospital
Principal Investigator: Ching-Sheng Hsu, MD Buddhist Tzu Chi General Hospital
Principal Investigator: Sheng-Shun Yang, MD Taichung Veterans General Hospital
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dr. Jia-Horng Kao, National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT00495131     History of Changes
Other Study ID Numbers: 200705080M
Study First Received: June 29, 2007
Results First Received: December 21, 2008
Last Updated: September 7, 2009
Health Authority: Taiwan: Department of Health

Keywords provided by National Taiwan University Hospital:
Chronic hepatitis C
Genotype 1
Interferon
Ribavirin

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Interferon-alpha
Interferon Alfa-2a
Interferons
Ribavirin
Peginterferon alfa-2a
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Antimetabolites

ClinicalTrials.gov processed this record on July 23, 2014