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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Severance Hospital
Kangbuk Samsung Hospital
Konkuk University Hospital
Chung-Ang University
Ajou University
Inha University Hospital
Soonchunhyang University Hospital
The Catholic University of Korea
Hallym University Medical Center
Kyungpook National University
Keimyung University
Korea University Anam Hospital
Korea University
Hanyang University
Inje University
Pusan National University Hospital
Bristol-Myers Squibb
Information provided by:
Yonsei University
ClinicalTrials.gov Identifier:
NCT00823550
First received: January 14, 2009
Last updated: December 15, 2010
Last verified: January 2009
  Purpose

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.


Condition Intervention Phase
Hepatitis B, Chronic
Drug: Entecavir
Drug: Lamivudine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Yonsei University:

Primary Outcome Measures:
  • Time to disease progression as defined by the first occurrence of any of the cirrhosis compolications [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 462
Study Start Date: January 2009
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
entecavir 0.5 mg QD
Drug: Entecavir
entecavir 0.5 mg QD
Other Name: Baraclude 0.5mg
Active Comparator: B
lamivudine 100 mg QD
Drug: Lamivudine
lamivudine 100 mg QD
Other Name: Zeffix 100mg

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)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00823550

Locations
Korea, Republic of
Severance Hospital
Seoul, Korea, Republic of
Sponsors and Collaborators
Yonsei University
Severance Hospital
Kangbuk Samsung Hospital
Konkuk University Hospital
Chung-Ang University
Ajou University
Inha University Hospital
Soonchunhyang University Hospital
The Catholic University of Korea
Hallym University Medical Center
Kyungpook National University
Keimyung University
Korea University Anam Hospital
Korea University
Hanyang University
Inje University
Pusan National University Hospital
Bristol-Myers Squibb
Investigators
Study Chair: Kwnag-Hyub Han, MD Yonsei Univsersity College of Medicine
Study Director: Jun Yong Park, MD Yonsei Univsersity College of Medicine
  More Information

No publications provided

Responsible Party: Kwang-Hyub Han, Department of Internal Medicine, Yonsei University College of Medicine
ClinicalTrials.gov Identifier: NCT00823550     History of Changes
Other Study ID Numbers: 4-2008-0296
Study First Received: January 14, 2009
Last Updated: December 15, 2010
Health Authority: Korea: Food and Drug Administration

Keywords provided by Yonsei University:
Chronic hepatitis B
Advanced fibrosis
Lamivudine
Entecavir

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Liver Diseases
Hepatitis B, Chronic
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Hepatitis, Chronic
Lamivudine
Entecavir
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on September 18, 2014