Overview

Adding Adefovir Dipivoxil Versus Switching to Entecavir in Patients With Lamivudine-resistant Chronic Hepatitis B

Status:
Completed
Trial end date:
2012-10-01
Target enrollment:
0
Participant gender:
All
Summary
Antiviral resistance mutations limit the efficacy of therapy for chronic hepatitis B. At year 2, resistance to adefovir may occur as high as 25% in patients with history of lamivudine resistance. Resistance to entecavir is reported to be 10% in lamivudine refractory patients during the same period. However, combination of lamivudine and adefovir decreased the adefovir resistance rate as low as 0% in the recent studies. By overcoming the antiviral resistance, the efficacy of therapy will be maximized. This study is intended to compare the efficacy of two strategies, combination of lamivudine and adefovir vs. entecavir monotherapy in patients with lamivudine resistance.
Phase:
Phase 4
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Korea University
Collaborator:
GlaxoSmithKline
Treatments:
Adefovir
Adefovir dipivoxil
Entecavir
Lamivudine
Criteria
Inclusion Criteria:

1. Chronic hepatitis B patients (positive HBsAg > 6 months)

2. Age > 16 year old

3. Serum alanine aminotransferase (ALT) >1.5 x ULN

4. History of treatment with lamivudine more than 6 months

5. Proven lamivudine resistant mutation

6. HBV DNA level> 20000 IU/mL

7. Compensated liver disease (Child-Pugh-Turcotte score over 7; prothrombin time
prolonged more than 3 sec above ULN or INR over 1.5; serum albumin >3 g/dL; total
bilirubin <2.5 mg/dL; No history of variceal bleeding, ascites, or hepatic
encephalopathy)

8. Patients willing to give informed consent

Exclusion Criteria:

1. Out of inclusion criteria

2. Any one of following

- Serum phosphorus level under 2.4 mg/dL

- Serum creatinine level over 1.5 mg/dL or creatinine clearance <50 mL/min

- Absolute neutrophil count lower than 1000 cell/mL

- Hb level under 10 g/dL (male), under 9 g/dL (female)

- Serum AFP >100 ng/mL

3. History of treatment with interferon-a, thymosin-alfa 1, or nucleos(t)ide analogue
other than lamivudine in 6 months of screening

4. Recipient of organ transplantation

5. Positive antibody test to HIV, HCV or HDV

6. Pregnant or breast feeding women

7. Patients with hepatocellular carcinoma or uncontrolled malignant disease

8. Habitual alcohol drinker (>140 g/week for men, >70 g/week for women)