Compare Continuing Lamivudine Plus Adefovir or Adefovir Versus Switching to Entecavir Plus Adefovir in Patients With LAM-resistant Chronic Hepatitis B

Study Overview
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Brief Summary
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The purpose of this study is to compare efficacy and safety of continuing Lamivudine plus Adefovir or Adefovir versus switching to Entecavir plus Adefovir in patients with LAM-resistant chronic hepatitis B who have suboptimal response to Lamivudine plus Adefovir or Adefovir

Official Title
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Efficacy and Safety of Continuing Lamivudine Plus Adefovir or Adefovir Versus Switching to Entecavir Plus Adefovir in Patients With Chronic Hepatitis B Who Have Resistant Mutants to Lamivudine and Show Suboptimal Response to Combination of Lamivudine Plus Adefovir or Adefovir Monotherapy

Conditions
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Hepatitis B, Chronic

Intervention / Treatment
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* Drug: Lamivudine
* Drug: Adefovir
* Drug: Entecavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic hepatitis B Age ≥ 20 year old Currently taking Lamivudine and Adefovir combination therapy or Adefovir monotherapy for chronic HBV infection for 24 weeks Proven Lamivudine resistant mutation HBV DNA levels at screening ≥ 15 IU/mL Females must be post-menopausal, unable to conceive, or test negative for pregnancy via urine test Patient is able to give written informed consent prior to study start and to comply with the study requirements Exclusion Criteria: A history or current of decompensated cirrhosis or hepatocellular carcinoma Currently receiving antiviral, immunomodulatory, cytotoxic or corticosteroid therapy Co-infected with HCV or HIV A history of organ transplantation Pregnant or breast-feeding Current clinically relevant of abuse of alcohol or drugs. Significant immunocompromised, gastrointestinal, renal(serum creatinine ≥ 1.5 mg/dL), hematological, psychiatric, bronchopulmonary, biliary diseases excluding asymptomatic GB stone, neurological, cardiac, oncologic, allergic disease or medical illness that in the investigator's opinion might interfere with therapy malignancy in previous 5 years

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lamivudine plus Adefovir or Adefovir<br>Lamivudine+Adefovir or Adefovir for 48 weeks | Drug: Lamivudine<br>* Lamivudine 100mg/day orally<br>Drug: Adefovir<br>* Adefovir 10mg/day orally<br>|
| Experimental: Entecavir plus Adefovir<br>Entecavir+Adefovir for 48 weeks | Drug: Adefovir<br>* Adefovir 10mg/day orally<br>Drug: Entecavir<br>* Entecavir 1mg/day orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with HBV DNA<15IU/mL |  | week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with HBV DNA<15IU/mL |  | Day1, week12, week 24, week 36, week 48 | 
| The change of HBV DNA from the baseline |  | week 48 | 
| Proportion of patients with ALT normalization |  | Day1, week12, week 24, week 36, week 48 | 
| Proportion of patients with HBeAg loss and/or seroconversion |  | Day1, week12, week 24, week 36, week 48 | 
| The change of HBsAg from the baseline |  | week 48 | 
| Proportion of patients with HBsAg loss and/or seroconversion |  | week 24, week 48 | 
| Proportion of patients who experienced virologic breakthrough |  | week 48 | 
| Assessment the safety in all patients (composite measure of AE, labs, phys. exam, vital signs) | Composite outcome measure consisting of multiple measures, including: Number of patients with Adverse events( including SAEs) Frequency and severity of Abnormalities in laboratory examinations; BUN, Albumin, AST, ALT,GGT, Creatinine, Hemoglobin, Hematocrit, Platelet Count, Prothrombin time Number of patients with Abnormalities in physical examinations; Eyes/Ears/Nose/Throat, Respiratory, Cardiovascular, Dermatological, Abdominal, Musculoskeletal, Other Number of patients with Abnormalities in vital signs ; pulse rate( beats per minute), Blood pressure(mmHg), Height(cm), weight(kg) | week 48 |