Clinical trial NCT00625560: Continuing Lamivudine vs Switching to Entecavir in Patients With Detectable HBV DNA
Official title: Randomized, Open-Labelled Study Evaluating the Antiviral Efficacy, Safety, and Tolerability of Continuing Lamivudine Therapy or Switching to Entecavir in Subjects With Chronic Hepatitis B With Detectable HBV DNA
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hepatitis B, Chronic
Keywords: Chronic hepatitis B
Lamivudine
Entecavir
Lead sponsor: Yonsei University
Sponsor class: OTHER
Collaborators: name: Pusan National University Hospital
First posted: 2008-02-28
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, open-labelled, prospective 96-week study comparing the antiviral efficacy and safety of switching to entecavir 1 mg QD from lamivudine versus maintaining lamivudine 100 mg QD treatment in HBV-infected subjects currently receiving lamivudine monotherapy.

Detailed description: Entecavir has a higher potent antiviral efficacy and a lower drug resistance rate than Lamivudine in nucleoside-naïve CHB patients. The prompt switch from Lamivudine to Entecavir in patients who have insufficient hepatitis B virus suppression (HBV DNA ≥ 60 IU/mL by PCR) may lead to full viral suppression to undetectable level by PCR method. The prompt switch from Lamivudine to Entecavir in patients who have insufficient hepatitis B virus suppression (HBV DNA ≥ 60 IU/mL) may preclude development of drug resistance. The results of this study will provide a rationale for switch treatment from one antiviral to another one, especially from LAM to ETV.

Eligibility criteria: Inclusion Criteria:

* Adult subjects (18-70 years of age) currently taking lamivudine monotherapy for chronic HBV infection for at least 6 months with ≥ HBV DNA 60 IU/mL level and HBeAg positive at baseline.

Exclusion Criteria:

* All subjects will be tested for presence of M204V/I mutations in the YMDD motif at baseline. Subjects with M204V/I mutations in the YMDD motif at baseline are not eligible for the study.
* Subjects treated with other antiviral drugs (e.g. adefovir) in combination with lamivudine are not eligible for this study.
* Subjects should have ALT \< 10 x ULN, and no evidence of hepatocellular carcinoma.
* Subjects should be without serological evidence of co-infection with HCV, HIV, or HDV.
* Subjects with decompensated liver disease, as well as pregnant or breast-feeding women, will not be eligible for the study.

Primary outcomes:
measure: Percentage number of patients with HBV DNA < 60 IU/mL (Undetectable serum HBV DNA by PCR method) while on randomized therapy
timeFrame: at Week 96
Secondary outcomes:
measure: Percentage number of patients with HBV DNA < 60 IU/mL while on randomized therapy
timeFrame: at Week 48
measure: Percentage number of patients who developed drug resistant mutations while on randomized therapy
timeFrame: at Week 48 and Week 96
measure: Change from baseline in mean HBV DNA
timeFrame: at Week 48 and 96
measure: Percentage number of patients who achieved ALT normalization, HBeAg loss, HBe seroconversion, HBsAg loss and HBs seroconversion
timeFrame: at Week 48 and 96
measure: Cumulative discontinuation rates due to lamivudine or entecavir resistance mutations and clinical breakthrough Safety assessment
timeFrame: Follow up period
Other outcomes:
Locations:
city: Busan
country: Korea, Republic of
facility: Pusan National University School of Medicine
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
Study officials:
affiliation: Yonsei Univsersity College of Medicine
name: Sang Hoon Ahn, M.D.Ph.D
role: STUDY_CHAIR
affiliation: Yonsei University
name: Do Young Kim, M.D.
role: STUDY_DIRECTOR
affiliation: Yonsei University
name: Jun Yong Park, M.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Pusan National University
name: Jeong Heo, M.D.Ph.D
role: STUDY_DIRECTOR
References: