Antiviral Therapy in Hepatitis B Virus (HBV)-Related Advanced Liver Disease Patients

Phase 4

• Conditions: Hepatitis B, Chronic
• Interventions: Drug: Entecavir; Drug: Lamivudine

• Registration Number: NCT00823550
• Lead Sponsor: Yonsei University

Brief Summary

This is a randomized, open label, phase IV, multicenter study for efficacy and safety of lamivudine versus entecarvir therapy in HBV-related advanced liver disease patients with high viral load and normal or slightly elevated transaminase.

Detailed Description

Currently, treatment guidelines for the management of chronic hepatitis B (CHB) recommend that patients with serum HBV DNA \> 105 copies/ml and elevated ALT levels greater than two times the upper limit of normal (ULN) are obvious candidates for antiviral therapy. Guidelines also suggest that antiviral therapy be considered in CHB patients with high viral load, if a biopsy shows significant liver disease despite ALT ≤ 2× ULN. Data from recent trials in hepatitis B patients who present with normal to minimally elevated ALT (≤ 2× ULN) indicate that significant hepatic pathology could still be found. Serum ALT level may not accurately predict activity of liver damage. ALT is a poor predictor of outcome and therefore is not a suitable criterion for antiviral therapy in chronic hepatitis B infection. Also, a recent large randomized controlled clinical trial comparing lamivudine maintenance and placebo in advanced fibrosis (Ishak fibrosis score ≥ 4) suggests that sustained viral suppression with antiviral therapy is linked to reduced risk for disease progression. (Liaw YF et al. NEJM 2004;351:1521-1531)

Study Timeline

• Status Verified: 2009-01
• Study Start: 2009-01
• Study First Submitted: 2009-01-14
• Study First Submitted QC: 2009-01-14
• Study First Posted: 2009-01-15
• Last Update Submitted: 2010-12-15
• Last Update Posted: 2010-12-16
• Primary Completion: 2014-07
• Study Completion: 2015-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 462

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A	Entecavir	entecavir 0.5 mg QD
B	Lamivudine	lamivudine 100 mg QD

Primary Outcome Measures

Name	Time	Method
Time to disease progression as defined by the first occurrence of any of the cirrhosis compolications	5 years

Secondary Outcome Measures

Name	Time	Method
Proportion of patients achieving either HBV DNA level ≤ 60 IU/mL Proportion of patients with ALT normalization Proportion of patients with HBeAg loss and seronconversion Proportion of patients with virologic breakthrough	at months 12, 24, 36, 48, and 60

Trial Locations

Locations (1)

Severance Hospital; 🇰🇷 Seoul, Korea, Republic of