Clinical trial NCT00543244: Early Prediction of Successful Treatment for Chronic Hepatitis C Virus Infection in Taiwan
Official title: Early Prediction of Successful Treatment for Chronic Hepatitis C Virus Infection in Taiwan
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Chronic Hepatitis C
Keywords: Chronic hepatitis C
Pegylated interferon
Ribavirin
Virokinetics
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
Collaborators: name: National Science and Technology Council, Taiwan
First posted: 2007-10-12
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with chronic hepatitis C virus infection who receive pegylated interferon plus ribavirin for an overall of 24-48 weeks

Brief summary: Hepatitis C virus (HCV) infection is a global health problem, which may lead to chronic hepatitis, cirrhosis, hepatic decompensation and hepatocellular carcinoma (HCC). Recently, treatment with peginterferon alfa plus ribavirin has become the standard of care for patients with chronic hepatitis C. While genotype 2 patients can have higher sustained virologic response (SVR) rates to 80-90%, genotype 1 patients generally have low SVR rates of only 40-50%. In contrast, genotype 1 Taiwanese patients have superior SVR rates than those in Western countries. Despite the overall improved response to this combination therapy, more than 75% of patients suffer from treatment-related adverse events and the costs remain high, which make individualized therapy of paramount importance to maximize treatment response and minimize adverse events.

HCV viral kinetics with interferon-based therapies have been studied recently to evaluate patient responses. Early viral kinetics shown to have favorable SVR rates, which make shorter treatment duration possible. However, different viral kinetics were found through ethnicity. Recently, a pilot study to evaluate the viral kinetics of 6 Taiwanese patients with HCV infection who received peginterferon alfa plus ribavirin therapy has shown superior early viral kinetics to those in Caucasian patients. Based on the favorable SVR rates in treating Taiwanese patients with chronic hepatitis C, the investigators aimed to conduct a large confirmatory study to evaluate the viral kinetics and try to define the optimal treatment for these patients.

Detailed description: Hepatitis C virus (HCV) infection is a global health problem, which may lead to chronic hepatitis, cirrhosis, hepatic decompensation and hepatocellular carcinoma (HCC). \[1,2\] Recently, treatment with peginterferon alfa plus ribavirin has become the standard of care for patients with chronic hepatitis C. While genotype 2 patients can have higher sustained virologic response (SVR) rates to 80-90%, genotype 1 patients generally have low SVR rates of only 40-50%. \[3-5\] In contrast, genotype 1 Taiwanese patients have superior SVR rates that those in Western countries. \[6,7\] Despite the overall improved response to this combination therapy, more than 75% of patients suffer from treatment-related adverse events and the costs remain high, \[8,9\] which make individualized therapy of paramount importance to maximize treatment response and minimize adverse events.

HCV viral kinetics with interferon-based therapies have been studied recently to evaluate patient responses. \[10-14\] Early viral kinetics shown to have favorable SVR rates, which make shorter treatment duration possible. \[15-18\] However, different viral kinetics were found through ethnicity. \[19-23\] Recently, a pilot study to evaluate the viral kinetics of 6 Taiwanese patients with HCV infection who received peginterferon alfa plus ribavirin therapy has shown superior early viral kinetics to those in Caucasian patients. \[24\] Based on the favorable SVR rates in treating Taiwanese patients with chronic hepatitis C, the investigators aimed to conduct a large confirmatory study to evaluate the viral kinetics and try to define the optimal treatment for these patients.

Eligibility criteria: Inclusion Criteria:

* Treatment naïve
* Over 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
* 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
* Unwilling to receive serial blood sampling during the study

Primary outcomes:
measure: Sustained virologic response (SVR)
timeFrame: 1~1.5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Ramat-Gan
country: Israel
facility: Faculty of Life Sciences, Bar-Ilan University
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: Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel
name: Avidan Uriel Neumann, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Taiwan University Hospital
name: Chen-Hua Liu, MD
role: PRINCIPAL_INVESTIGATOR
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