Peginterferon Alfa-2a Plus Ribavirin for Chronic Hepatitis C/Hepatitis B Co-Infection and Chronic Hepatitis C
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ClinicalTrials.gov Identifier: NCT00154869
Recruitment Status : Unknown
Verified August 2005 by National Taiwan University Hospital. Recruitment status was: Recruiting
The investigators' pilot study indicates that hepatitis C virus (HCV)- and hepatitis B virus (HBV)-coinfected patients with predominantly active hepatitis C and those with predominantly active hepatitis B may need different anti-viral regimens. Since in the majority of these coinfected patients the hepatitis activity is more likely due to HCV than to HBV, the optimal therapeutic regimen for HCV- and HBV-coinfected patients with predominantly active hepatitis C will first be investigated. The combination therapy using pegylated interferons (IFNs) such as PEG-IFN alfa-2a has been shown to have a superior efficacy than that using conventional IFN in the treatment of monoinfected chronic hepatitis C. This new combination therapy might also further enhance the treatment efficacy in HCV- and HBV- coinfected patients. The investigators therefore propose to initiate a trial comparing the efficacy of pegylated IFN plus ribavirin (RBV) in dual chronic hepatitis B and C versus that in chronic hepatitis C only, for both HCV genotype 1 and 2/3 patients. The efficacy using a 24-week combination therapy in the sustained clearance of serum HCV RNA is equivalent to that using a 48-week combination therapy in patients with HCV genotype non-1 [Hadziyannis et al, EASL 2002]. A 48-week course of pegylated IFN and RBV combination therapy, in contrast, has been shown to yield a better efficacy in the sustained clearance of serum HCV RNA in patients with HCV genotype 1 than a 24-week combination therapy in western countries [Hadziyannis et al, EASL 2002; Poynard et al, 1998]. The primary objective of the current proposal is to investigate and compare the efficacy of combination therapy using pegylated IFN plus RBV on the clearance of serum HCV RNA in both dually infected patients with a dominant HCV infection and HCV monoinfected patients. Therefore, in this proposal, the treatment duration will be 24 weeks for HCV genotype 2/3 in patients with dual chronic hepatitis C and B and in patients with monoinfected HCV, and will be 48 weeks for HCV genotype 1 in patients with dual chronic hepatitis C and B and in patients with monoinfected HCV.
An Open Label, Comparative, Multi-Center Study, to Evaluate the Efficacy and Safety of Peginterferon Alfa-2a Plus Ribavirin in the Treatment of Patients With Chronic Hepatitis C/Hepatitis B Co-Infection and Chronic Hepatitis C
Study Start Date :
Study Completion Date :
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To demonstrate the efficacy of peginterferon alfa-2a (PEG-IFN alfa-2a) (Pegasys®) plus ribavirin (RBV) for sustained virological response (SVR) in HBV-coinfected versus monoinfected chronic hepatitis C (CHC) patients
Secondary Outcome Measures :
To demonstrate the efficacy of peginterferon alfa-2a (PEG-IFN alfa-2a) (Pegasys®) plus ribavirin (RBV) on the reduction of HCV viremia after 24 and 48 weeks of treatment (depending on genotype) in coinfected versus monoinfected CHC patients
To demonstrate the efficacy of PEG-IFN alfa-2a plus RBV in dual chronic hepatitis C and B on:
1) the biochemical response rate
2) the score of histologic change
3) serum HBV DNA disappearance
4) HBsAg disappearance
5) combined response of HBV DNA disappearance and normalization of ALT
6) end of treatment virological response
To assess the influence of serum HBV load on the clearance of serum HCV RNA, the loss of serum HBV DNA, and normalization of serum ALT
To assess the influence of HBV genotype on the clearance of serum HCV RNA, the loss of serum HBV DNA, and normalization of serum ALT
To assess the safety profile of the PEG-IFN alfa-2a plus RBV combination therapy in dual chronic hepatitis C and B
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Ages Eligible for Study:
18 Years and older (Adult, Senior)
Sexes Eligible for Study:
Accepts Healthy Volunteers:
Male and female patients >= 18 years of age will be recruited.
Patients with dual chronic hepatitis C and B must be positive for both anti-HCV and HBsAg for more than 6 months and HCV RNA quantifiable at 600 IU/mL (by the COBAS AMPLICOR HCV MONITOR® Test version 2.0).
Patients must not be positive for HBeAg.
Patients with monoinfected chronic hepatitis C must be positive for anti-HCV for more than 6 months and HCV RNA quantifiable at 600 IU/mL (by the COBAS AMPLICOR HCV MONITOR® Test version 2.0). Patients must not be positive for HBsAg.
All patients must:
Be treatment naïve for the hepatitis disease or have had treatment failure to previous interferon monotherapy or treatment failure to previous lamivudine therapy.
Present with elevated serum ALT levels at least 1.5 times the upper limit of normal, documented on two occasions (at least one month apart), within six months prior to enrollment
Present with liver biopsy findings compatible with the diagnosis of chronic liver disease (the liver biopsy needs to be taken within 52 weeks prior to the first dose of study drug)
Have adequate liver reserve (defined as equal to or better than Child-Pugh Class A)
Present with WBC 3500/mm3, ANC 1500/mm3, and platelets 90,000/mm3
Be drug addicts or have any history or histological evidence of alcohol abuse, or currently receive prescriptions that may cause hepatotoxicity
Present with hemoglobin <12.0 gm/dl for females and <13.0 gm/dl for males
Signs or symptoms of hepatocellular carcinoma
Any investigational drug ? 6 weeks prior to the first dose of study drug
Have renal insufficiency (serum creatinine concentration >1.5 x upper limit of normal at screening; upper limit depending on lab at each site)
Patients with documented or presumed coronary artery disease or cerebrovascular disease should not be enrolled if, in the judgment of the investigator, an acute decrease in hemoglobin by up to 4 g/dL (40 g/L) (as may be seen with ribavirin therapy) would not be well-tolerated.
History of major organ transplantation with an existing functional graft
History or other evidence of severe illness, malignancy or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study
Thyroid dysfunction not adequately controlled (TSH and T4 levels out of normal range)
Evidence of severe retinopathy (e.g., CMV retinitis, macular degeneration) or clinically relevant ophthalmological disorder due to diabetes mellitus or hypertension
Have been exposed to hepatotoxic substances which might be the cause of hepatitis
Be pregnant, lactating or not practicing two adequate forms of birth control, such as oral contraceptives or intrauterine devices
Be seropositive for anti-HIV or anti-delta or anti-HAV IgM Ab
History of severe psychiatric disease, especially depression, characterized by a suicide attempt, hospitalization for psychiatric disease, or a period of disability as a result of psychiatric disease
Have AFP (alpha-fetoprotein) greater than 20 ng/ml; in case of elevated AFP, abdomen ultrasonography is required to exclude the possibility of HCC.
History of severe cardiac disease (e.g., NYHA Functional Class III or IV, myocardial infarction within 6 months, ventricular tachyarrhythmias requiring ongoing treatment, unstable angina or other significant cardiovascular diseases).
Have a history of asthma (see above) or drug allergy which may lead to the hypersensitivity to ribavirin