Efficacy of Clevudine Plus Lamivudine for Lamivudine-resistant Chronic Hepatitis B Patients

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the optimal antiviral treatment for lamivudine resistant hepatitis B patients.

Detailed Description
-----------------
Lamivudine with adefovir combination therapy has been known as effective antiviral therapy for lamivudine resistant chronic hepatitis B patients. It is superior to adefovir monotherapy since the incidence of viral breakthrough of combination therapy used to be less than that of adefovir monotherapy in lamivudine resistant chronic hepatitis B patients. Clevudine, which is being marketed in Korea, is a nucleoside analogue of the unnatural beta-L configuration that has potent activity against HBV. It has demonstrated potent antiviral efficacy and significant biochemical improvement after 24 weeks of therapy. We hypothesized that clevudine plus adefovir combination therapy for lamivudine resistant patients might be as effective as the lamivudine plus adefovir combination therapy. In detail, we designed to perform this clinical study comparing the combination of clevudine and adefovir with lamivudine plus adefovir in lamivudine resistant chronic hepatitis B patient. Total treatment duration of both groups will be 12 months, and compare the efficacy of antiviral effects of these drugs.

Official Title
-----------------
A Multicenter, Randomized, Controlled Tial of Combination Therapy for Lamivudine-resistant Chronic Hepatitis B Patient: Comparing Clevudine Plus Adefovir With Lamivudine Plus Adefovir

Conditions
-----------------
Chronic Hepatitis B

Intervention / Treatment
-----------------
* Drug: adefovir
* Drug: clevudine
* Drug: lamivudine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: HBsAg positive and anti-HBs negative more than 6 months YMDD mutation (+)during lamivudine therapy Serum ALT more than two times upper normal value Exclusion Criteria: HAV IgM Ab + and/or HCV Ab+ and/or HDV Ab and/or HIV Av+ The sign of decompensated liver disease Pregnant or lactating woman The history of hemoglobinopathy, autoimmune hepatitis, alcoholic liver disease Hemoglobin less than 8 g/dL (male), 7.5g/dL (female) or neutrophil count less than 1500/mm3 or platelet count less than 50,000/mm3 Serum creatinine more than 1.5 times upper normal limit value The sign of malignancy or suggestive of malignancy or the history of malignancy, the recurrence rate within 2 years of which is more than 20%

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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<br> | Drug: adefovir<br>* adefovir 10mg<br>* Other names: Hepsera;Drug: lamivudine<br>* lamivudine 100mg<br>* Other names: Zeffix;|
| Active Comparator: Clevudine plus adefovir<br> | Drug: adefovir<br>* adefovir 10mg<br>* Other names: Hepsera;Drug: clevudine<br>* clevudine 30mg<br>* Other names: Levovir;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HBV DNA titer < 300 copies/mL |  | 48 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Normalization of serum ALT, loss of HBeAg and HBsAg, incidence of adefovir resistance |  | 48 week | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Chronic hepatitis B, lamivudine resistance, clevudine