Chronic Hepatitis B
Conditions
Keywords
Chronic Hepatitis B, Telbivudine, Adefovir, Lamivudine resistance
Brief summary
Lamivudine had been widely used for treatment-naïve chronic hepatitis B patients. However, development of antiviral resistance has been known as the major drawback: Incidence of lamivudine resistance was reported to be approximately 70% after 5 years (Lok AS et al, 2003). For the treatment of lamivudine resistance, adefovir has been widely used (Lok AS and McMahon B, 2009). However, switching to adefovir monotherapy was also reported to be at high risk of resistance, 25% at year 2 (Yeon JE et al, 2006). Recently, adding adefovir on lamivudine was shown to be superior to switching to adefovir monotherapy by decreasing the adefovir resistance (Rapti I et al, 2007, Lampertico P et al, 2007). However, combination of adefovir and lamivudine does not increase antiviral activity compared with adefovir monotherapy in patients with lamivudine resistance (Peters MG et al, 2004). As many patients are still viremic with the treatment of lamivudine and adefovir over 1 year, the investigators need more potent combination of the drugs. Telbivudine is a new nucleoside analogue with potent antiviral activity. The previous phase III study has shown the superiority of telbivudine over lamivudine in HBeAg positive and negative subjects (Lai CL et al, 2007). Therefore, telbivudine plus adefovir may be a better treatment option than lamivudine plus adefovir for the lamivudine-resistant chronic hepatitis B patients. No study assessing the efficacy of telbivudine plus adefovir has been conducted for these patients. The aim of this study is to evaluate the safety and efficacy of telbivudine plus adefovir compared with lamivudine plus adefovir in lamivudine resistant chronic hepatitis B patients at the end of 1 year follow-up,
Interventions
DRUGtelbivudine plus adefovir
telbivudine 600 mg qd plus adefovir 10 mg qd
lamivudine 100 mg qd plus adefovir 10mg qd
Sponsors
Korea University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. HBeAg positive or negative chronic hepatitis B patients (positive HBsAg more than 6 months) 2. Age ≥ 18 years old, and ≤70 years old 3. Previous treatment with lamivudine more than 6 months 4. Being on lamivudine at the time of screening 5. Confirmed genotypic resistance to lamivudine by RFMP (rtM204V or I) 6. Presence of virologic breakthrough ≥1 log increase of HBV DNA above na dir) 7. HBV DNA ≥ 20,000 IU/mL 8. Patient willing to give an informed consent (If patient is \<20 years old, the parent or legal guardian also need to give an informed consent)
Exclusion criteria
1. Out of inclusion criteria 2. Presence of adefovir resistance (rtA181T or V, rtN236T) by RFMP assay 3. Laboratory abnormalities as follows at screening: AFP\>100 ng/mL, serum phosphorous level\<2.4 mg/dL, serum creatinine level\> 1.5 mg/dL or creatinine clearance \< 50 mL/min 4. Patient with a history of decompensated liver disease: Any patients with a history of ascites, hepatic encephalopathy, variceal bleeding, jaundice, or CTP\>7 points should be excluded. 5. History of treatment with nucleos(t)ide analogues other than lamivudine more than 4 weeks 6. History of immune modulatory drugs (interferon, thymosin-alfa) within 24 weeks of screening 7. Liver transplant patient 8. Patient co-infected with HIV, HCV, or HDV 9. Patient with metabolic or genetic liver disease that may affect serum ALT level 10. Habitual alcohol consumption (\>140 g/week for male, \>70 g/week for female) 11. Patient not able to stop drugs that may affect ALT or HBV DNA level during study periods (ie. Steroid, immune-suppressants, non-steroidal anti-inflammatory drugs, acetaminophen,) 12. Pregnant or lactating woman 13. Menstruating woman unwilling to use appropriate methods of contraception (ie. Condom, oral contraceptives, tubal ligation) 14. Patient with hepatocellular carcinoma (treated or not treated) 15. Patient with any untreated malignancy 16. Patient with history of malignancy cured within 5 years of screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The mean reduction of serum HBV DNA from the baseline at week 52. | up to the end of year 1 (52 weeks) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HBV DNA undetectability(<20 IU/mL) | up to the end of year 1 (52 weeks) | At the end of year 1 in the two groups, HBV DNA undetectability by real time PCR will be assessed. |
| mean serum HBV DNA level | up to the end of year 1 (52 weeks) | — |
| rates of HBeAg loss | up to the end of year 1 (52 weeks) | — |
| rate of HBeAg seroconversion at week 52. | up to the end of year 1 (52 weeks) | — |
| rate of ALT normalization | up to the end of year 1 (52 weeks) | — |
Other
| Measure | Time frame |
|---|---|
| Antiviral resistance rate | up to the end of year 1 (52 weeks) |
Countries
South Korea
Contacts
Primary ContactHyung Joon Yim, M.D
Outcome results
None listed