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

NCT ID: NCT00823550

Last Updated: 2010-12-16

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 462 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-01-31
• Study Completion Date: 2015-07-31

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)

Conditions

Hepatitis B, Chronic

Keywords

Chronic hepatitis B; Advanced fibrosis; Lamivudine; Entecavir

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A

entecavir 0.5 mg QD

Group Type: EXPERIMENTAL

Entecavir

Intervention Type: DRUG

entecavir 0.5 mg QD

B

lamivudine 100 mg QD

Group Type: ACTIVE_COMPARATOR

Lamivudine

Intervention Type: DRUG

lamivudine 100 mg QD

Interventions

Entecavir

entecavir 0.5 mg QD

Intervention Type: DRUG

Lamivudine

lamivudine 100 mg QD

Intervention Type: DRUG

Other Intervention Names

Baraclude 0.5mg; Zeffix 100mg

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Severance Hospital

OTHER

Sponsor Role: collaborator

Kangbuk Samsung Hospital

OTHER

Sponsor Role: collaborator

Konkuk University Hospital

OTHER

Sponsor Role: collaborator

Chung-Ang University

OTHER

Sponsor Role: collaborator

Ajou University

OTHER

Sponsor Role: collaborator

Inha University Hospital

OTHER

Sponsor Role: collaborator

Soonchunhyang University Hospital

OTHER

Sponsor Role: collaborator

The Catholic University of Korea

OTHER

Sponsor Role: collaborator

Hallym University Medical Center

OTHER

Sponsor Role: collaborator

Kyungpook National University Hospital

OTHER

Sponsor Role: collaborator

Keimyung University

OTHER

Sponsor Role: collaborator

Korea University Anam Hospital

OTHER

Sponsor Role: collaborator

Korea University

OTHER

Sponsor Role: collaborator

Hanyang University

OTHER

Sponsor Role: collaborator

Inje University

OTHER

Sponsor Role: collaborator

Pusan National University Hospital

OTHER

Sponsor Role: collaborator

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Yonsei University

OTHER

Sponsor Role: lead

Responsible Party

Department of Internal Medicine, Yonsei University College of Medicine

Principal Investigators

Kwnag-Hyub Han, MD

Role: STUDY_CHAIR

Yonsei Univsersity College of Medicine

Jun Yong Park, MD

Role: STUDY_DIRECTOR

Yonsei Univsersity College of Medicine

Locations

Severance Hospital

Seoul, , South Korea

Countries

South Korea

Other Identifiers

4-2008-0296

Identifier Type: -

Identifier Source: org_study_id