Entecavir Plus Adefovir in Lamivudine-Resistant Chronic Hepatitis B Patients Who Fail Lamivudine Plus Adefovir
Condition: Hepatitis B, Chronic
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic
Intervention: Adefovir; Entecavir; Lamivudine
Intervention description: Adefovir dipivoxil (Hepsera) 10 mg/day orally for 104 weeks; Entecavir 1 mg/day orally; Lamivudine (Zeffix) 100 mg/day orally
Intervention MeSH terms: Lamivudine; Adefovir; Adefovir dipivoxil; Entecavir
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 90.0
Sex: All
Minimum age: 16 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Chronic hepatitis B; lamivudine; adefovir; entecavir

Summary:

      The presence of persistent inadequate or suboptimal virologic response is a strong risk
      factor for viral resistance and breakthrough and also for disease progression of chronic
      hepatitis B, and thus, a change in therapy is required. The combination of entecavir (ETV)
      and adefovir (ADV) is a promising treatment for patients with lamivudine (LAM)-resistance who
      show suboptimal response to the combination of LAM and ADV.

      In this randomized, open labeled trial,the investigators will compare the efficacy of
      continuation of ADV plus LAM versus switch to ADV plus ETV in adults with LAM-resistant
      chronic hepatitis B who shows suboptimal response to the combination treatment of ADV and
      LAM.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female, 16 to 75 years of age

          2. Compensated liver disease(Child-Pugh class A)

          3. HBsAg positive at least 6 months or more

          4. HBeAg positive or negative

          5. Confirmation of Lamivudine-resistance HBV mutation anytime before the study

          6. Patients with suboptimal response (HBV DNA > 2000 IU/mL despite combination of
             Adefovir [10 mg/day] plus Lamivudine [100 mg/day] for 6 months or more). Serum HBV DNA
             should be determined by the PCR assay at the local laboratory at screening for this
             study

          7. Patient is ambulatory.

          8. Patient is willing and able to comply with the study drug regimen and all other study
             requirements.

          9. The patient is willing and able to provide written informed consent to participate in
             the study.

        Exclusion Criteria:

          1. Patient has a history of hepatocellular carcinoma (HCC) or findings suggestive of
             possible HCC, such as suspicious foci on imaging studies or elevated serum alpha
             fetoprotein (AFP) levels. In patients with such findings, HCC should be ruled-out
             prior to randomizing the patient for the present study.

          2. Patient previously received oral antiviral agent other than Lamivudine or Adefovir

          3. Patient has received interferon or other immunomodulatory treatment for HBV infection
             within 12 months before screening for this study.

          4. Patient has concomitant other chronic viral infection (HCV or HIV)

          5. Patient has evidence of renal insufficiency defined as serum creatinine > 1.5 mg/dL

          6. Patient has medical condition that requires use of systemic prednisolone or other
             immunosuppressive agent (including chemotherapeutic agent)

          7. Patient is currently abusing alcohol or illicit drugs, or has a history of alcohol
             abuse or illicit substance abuse within the preceding two years.

          8. Patient is pregnant or breastfeeding or willing to be pregnant

          9. Patient has one or more additional known primary or secondary causes of liver disease,
             other than hepatitis B (e.g., alcoholism, autoimmune hepatitis, malignancy with
             hepatic involvement, 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.).

         10. A history of treated malignancy (other than hepatocellular carcinoma) is allowable if
             the patient's malignancy has been in complete remission, off chemotherapy and without
             additional surgical intervention, during the preceding three years.

         11. Clinical signs of decompensated liver disease as indicated by any one of the
             following:

               -  serum bilirubin > 3 mg/dL

               -  prothrombin time > 6 seconds prolonged or INR >1.6

               -  serum albumin < 2.8 g/dL

               -  History of ascites, variceal hemorrhage, or hepatic encephalopathy

               -  Child-Pugh score ≥7