Clinical trial NCT00798460: Efficacy of Clevudine Plus Lamivudine for Lamivudine-resistant Chronic Hepatitis B Patients
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Chronic Hepatitis B
Keywords: Chronic hepatitis B
lamivudine resistance
clevudine
Lead sponsor: Inje University
Sponsor class: OTHER
Collaborators: name: Bukwang Pharmaceutical
First posted: 2008-11-26
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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%

Primary outcomes:
measure: HBV DNA titer < 300 copies/mL
timeFrame: 48 week
Secondary outcomes:
measure: Normalization of serum ALT, loss of HBeAg and HBsAg, incidence of adefovir resistance
timeFrame: 48 week
Other outcomes:
Locations:
city: Goyang
country: Korea, Republic of
facility: Ilsanpaik hospital
state: Gyunggi
Study officials:
affiliation: Department of Internal Medicine, Ilsanpaik hospital, Inje Univeristy, 2240 Daewha-dong, Ilsanseo-gu, Goyang, Gyunggi, Korea, 411-706
name: June Sung Lee, M.D.
role: PRINCIPAL_INVESTIGATOR
References: