Overview

This trial is active, not recruiting.

Condition hepatitis b, chronic
Treatments entecavir, lamivudine
Phase phase 4
Sponsor Yonsei University
Collaborator Severance Hospital
Start date January 2009
End date July 2014
Trial size 462 participants
Trial identifier NCT00823550, 4-2008-0296

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
entecavir 0.5 mg QD
entecavir Baraclude 0.5mg
entecavir 0.5 mg QD
(Active Comparator)
lamivudine 100 mg QD
lamivudine Zeffix 100mg
lamivudine 100 mg QD

Primary Outcomes

Measure
Time to disease progression as defined by the first occurrence of any of the cirrhosis compolications
time frame: 5 years

Secondary Outcomes

Measure
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
time frame: at months 12, 24, 36, 48, and 60

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion criteria - Male and female, 18 years of age or older - HBsAg positive for more than 6 months - Serum HBV DNA > 2,000 IU/ml - Serum ALT < 2 X ULN on two consecutive occasions at least 3 months apart - Naïve to nucleoside or nucleotide therapy - On liver biopsy, fibrosis score ≥ 3 according to METAVIR scoring system (within 2 years of Day 0) - If liver biopsy is not available, subjects must have two of the following items - Overt findings of cirrhosis by radiologic evidence (MRI, CT, US) - Gastrointestinal varices - Platelet count < 100,000,Splenomegaly (Spleen size - 12cm) - The patient who is willing and able to provide written informed consent to participate in this study Exclusion criteria - A history of SBP, variceal bleeding, HEP, HCC - Decompensated liver disease (Child-Pugh score > 10) - Co-infected with HCV or HIV - History of any other forms of liver disease. - Patient who is pregnant or breastfeeding - Treatment with immunosuppressive, immunomodulatory agents or antiviral agents within 6 months prior to study entry - A history of liver transplantation or planned for liver transplantation - A history of any other medical disease or condition that would make the patients unsuitable for the study. - Patient is currently abusing alcohol or illicit drugs or has a history of alcohol abuse or illicit substance abuse within the preceding 2 years. - Patient is enrolled or plans to enroll in another clinical trial of an investigational agent while participating in this study.

Additional Information

Official title 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
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)
Trial information was received from ClinicalTrials.gov and was last updated in December 2010.
Information provided to ClinicalTrials.gov by Yonsei University.