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A study to comparison of tenofovir monotherapy with entecavir-adefovir combination in suboptimal responder for lamivudine-adefovir rescue therapy in chronic hepatitis B patients with YMDD mutatio

Not Applicable
Completed
Conditions
Diseases of the digestive system
Registration Number
KCT0000627
Lead Sponsor
Soon Chun Hyang University Hospital Cheonan
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Completed
Sex
All
Target Recruitment
60
Inclusion Criteria

1) Age, 20 Years to 75 Years
2) HBsAg positive at least 6 months or more
3) Confirmed emergence of YMDD mutations (rtM204) with/without compensatory mutation (rtL180) with test for mutation profile and with virologic breakthrough (? serum HBV DNA > 1 log IU/mL at any time before screening
4) Received ADV-LAM combination therapy at least 24 weeks
5) Serum HBV DNA positive in real-time PCR assay despite continued preceding LAM and ADV combination therapy
6) Serum HBV DNA >60 IU/mL at screening for this study

Exclusion Criteria

1) Confirmed emergence of such drug resistant mutations (rtI169, rtT184, rtS202, rtM250) at any time before screening
2) Patient with decompensated cirrhosis (uncontrolled ascites, history of variceal bleeding, history of hepatic encephalopathy, Child-Pugh score > 8)
3) Patient has evidence of renal insufficiency defined as eGFR < 60 ml/min (using the Cockcroft-Gault equation)
4) Patient has received interferon or other immunomodulatory treatment for HBV infection in the 6 months before screening for this study.
5) Patient has medical condition that requires concurrent use of systemic corticosteroid or other immunosuppressive agent (including chemotherapeutic agent)
6) Patient is currently abusing alcohol (more than 40 g/day in men, 20 g/day in women) or illicit drugs
7) Patient has concomitant other chronic viral infection (HCV or HIV)
8)Patient has one or more additional known primary or secondary causes of liver disease, other than hepatitis B (e.g., autoimmune hepatitis, hemochromatosis, alpha-1 antitrypsin deficiency, Wilson's Disease, other congenital or metabolic conditions affecting the liver, congestive heart failure or other severe cardiopulmonary disease, etc.).
9) Patient is pregnant or breastfeeding
10) Patient has a history of HCC or findings suggestive of possible HCC, such as suspicious foci on imaging studies. In patients with such findings, HCC should be ruled-out prior to randomizing the patient for the present study.
11) A history of treated malignancy (other than HCC) is allowable if the patient's malignancy has been in complete remission, off chemotherapy and without additional surgical intervention, during the preceding three years.
12) Patient has severe bone disease (osteomalacia, chronic osteomyelitis, osteogenesis imperfect, osteochondroses)

Study & Design

Study Type
Interventional Study
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Proportion of patients with complete virological response (HBV-DNA < 60 IU/mL) at week 96
Secondary Outcome Measures
NameTimeMethod
Proportion of patients with resistance mutations to adefovir, entecavir, or tenofovir;Changes in serum HBV DNA level and mean levels during 96 weeks of treatment;Proportion of patients with normal ALT ;Proportion of patients with HBeAg loss or seroconversion;Changes in serum HBsAg levels during 96 weeks of treatment;Proportion of patients with developing adverse event and fatal complications, such as decompensated cirrhosis, hepatocellular carcinoma (HCC);Drug adherence and economic evaluations
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