Clinical trial NCT00495131: Randomized Trial of 24 or 48 Weeks of Peginterferon Alfa-2a Plus Ribavirin for HCV Genotype 1-infected Patients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hepatitis C, Chronic
Keywords: Chronic hepatitis C
Genotype 1
Interferon
Ribavirin
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
Collaborators: name: National Science and Technology Council, Taiwan
First posted: 2007-07-02
Enrollment: 308
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Sustained Virologic Response
timeFrame: 18 months
measure: Sustained Biochemical Response
timeFrame: 18 months
Secondary outcomes:
measure: Treatment-related Withdrawal Rate
timeFrame: 18 months
measure: Histologic Response
timeFrame: 18 months
Other outcomes:
Locations:
city: Douliou
country: Taiwan
facility: National Taiwan University Hospital, Yun-Lin Branch
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Buddhist Tzu Chi General Hospital
city: Taipei
country: Taiwan
facility: Far Eastern Memorial Hospital
city: Taipei
country: Taiwan
facility: Ren-Ai Branch, Taipei Municipal Hospital
Study officials:
affiliation: National Taiwan University Hospital
name: Jia-Horng Kao, MD, PhD
role: STUDY_CHAIR
affiliation: National Taiwan University Hospital
name: Ding-Shinn Chen, MD
role: STUDY_DIRECTOR
affiliation: National Taiwan University Hospital
name: Ming-Yang Lai, MD, PhD
role: STUDY_DIRECTOR
affiliation: National Taiwan University Hospital
name: Pei-Jer Chen, MD, PhD
role: STUDY_DIRECTOR
affiliation: National Taiwan University Hospital
name: Chun-Jen Liu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Taiwan University Hospital
name: Chen-Hua Liu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Taiwan University Hosptial, Yun-Lin Branch
name: Shih-Jer Hsu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ren-Ai Branch, Taipei City Hospital
name: Chih-Lin Lin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Far Eastern Memorial Hospital
name: Cheng-Chao Liang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Buddhist Tzu Chi General Hospital
name: Ching-Sheng Hsu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Taichung Veterans General Hospital
name: Sheng-Shun Yang, MD
role: PRINCIPAL_INVESTIGATOR
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