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

Primary Purpose

Hepatitis B, Chronic

Status

Unknown status

Phase

Phase 4

Locations

Korea, Republic of

Study Type

Interventional

Intervention

Entecavir

Lamivudine

About this trial

This is an interventional treatment trial for Hepatitis B, Chronic focused on measuring Chronic hepatitis B, Advanced fibrosis, Lamivudine, Entecavir

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Severance Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm Description

entecavir 0.5 mg QD

lamivudine 100 mg QD

Outcomes

Primary Outcome Measures

Time to disease progression as defined by the first occurrence of any of the cirrhosis compolications

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

Full Information

NCT ID

NCT00823550

First Posted

January 14, 2009

Last Updated

December 15, 2010

Sponsor

Yonsei University

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 Hospital, Keimyung University, Korea University Anam Hospital, Korea University, Hanyang University, Inje University, Pusan National University Hospital, Bristol-Myers Squibb

1. Study Identification

Unique Protocol Identification Number

NCT00823550

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2009

Overall Recruitment Status

Unknown status

Study Start Date

January 2009 (undefined)

Primary Completion Date

July 2014 (Anticipated)

Study Completion Date

July 2015 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor

Yonsei University

Collaborators

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatitis B, Chronic

Keywords

Chronic hepatitis B, Advanced fibrosis, Lamivudine, Entecavir

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

462 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

entecavir 0.5 mg QD

Arm Title

Arm Type

Active Comparator

Arm Description

lamivudine 100 mg QD

Intervention Type

Drug

Intervention Name(s)

Entecavir

Other Intervention Name(s)

Baraclude 0.5mg

Intervention Description

entecavir 0.5 mg QD

Intervention Type

Drug

Intervention Name(s)

Lamivudine

Other Intervention Name(s)

Zeffix 100mg

Intervention Description

lamivudine 100 mg QD

Primary Outcome Measure Information:

Title

Time to disease progression as defined by the first occurrence of any of the cirrhosis compolications

Time Frame

5 years

Secondary Outcome Measure Information:

Title

Time Frame

at months 12, 24, 36, 48, and 60

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kwnag-Hyub Han, MD

Organizational Affiliation

Yonsei Univsersity College of Medicine

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Jun Yong Park, MD

Organizational Affiliation

Yonsei Univsersity College of Medicine

Official's Role

Study Director

Facility Information:

Facility Name

Severance Hospital

City

Seoul

Country

Korea, Republic of

12. IPD Sharing Statement

Learn more about this trial

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

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