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

December 15, 2010 updated by: Yonsei University

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
462

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: A
entecavir 0.5 mg QD
Drug: Entecavir
entecavir 0.5 mg QD
Other Names:
  • Baraclude 0.5mg
Active Comparator: B
lamivudine 100 mg QD
Drug: Lamivudine
lamivudine 100 mg QD
Other Names:
  • Zeffix 100mg

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Time to disease progression as defined by the first occurrence of any of the cirrhosis compolications
Time Frame: 5 years
5 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
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
at months 12, 24, 36, 48, and 60

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Yonsei University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Bristol-Myers Squibb
Pusan National University Hospital
Korea University Anam Hospital
Korea University
Kyungpook National University Hospital
Inje University
Hanyang University
The Catholic University of Korea
Kangbuk Samsung Hospital
Severance Hospital
Soonchunhyang University Hospital
Hallym University Medical Center
Chung-Ang University
Konkuk University Hospital
Inha University Hospital
Keimyung University
Ajou University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Kwnag-Hyub Han, MD, Yonsei Univsersity College of Medicine
  • Study Director: Jun Yong Park, MD, Yonsei Univsersity College of Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2009

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2014

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 14, 2009

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 14, 2009

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 15, 2009

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 16, 2010

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 15, 2010

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 4-2008-0296

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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