Using Entecavir to Reduce Hepatitis in Highly Viremic HBV Patients During Anti-tuberculous Treatment (HBV)

November 7, 2012 updated by: National Taiwan University Hospital

Prophylactic Use of Entecavir to Reduce Hepatitis Flare in Highly Viremic HBV Patients With Active Tuberculosis Receiving Anti-tuberculous Treatment

Hepatitis during anti-tuberculous treatment (HATT) has been an obstacle in managing TB patients, especially in those with viral hepatitis. A previous study revealed the risk of HATT is significantly higher in TB patients with high serum hepatitis B virus (HBV) DNA level than those with low HBV DNA level. Based on these findings, we thus hypothesize that the risk of HATT in TB patients with high baseline serum HBV DNA level can be reduced by concomitant use of anti-HBV agent. In this proposal, we will conduct a prospective randomized clinical study to assess the reduction of HATT risk by using entecavir in TB patients with high baseline serum HBV DNA level, and to evaluate the risk of other treatment-related adverse events in two hospitals.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Tuberculosis (TB) remains one of the important infectious diseases worldwide. Timely implementation of optimized anti-tuberculous therapy is still the mainstay to prevent further transmission of TB. However, hepatitis during anti-tuberculous treatment (HATT) has been an obstacle in managing TB patients, especially in those with viral hepatitis. A previous study revealed the risk of HATT is significantly higher in TB patients with high serum hepatitis B virus (HBV) DNA level than those with low HBV DNA level (39% vs. 11%), the latter cases have a similar risk of HATT as those without viral hepatitis (14%). Based on these findings, we thus hypothesize that the risk of HATT in TB patients with high baseline serum HBV DNA level can be reduced by concomitant use of anti-HBV agent. In this proposal, we will conduct a prospective randomized clinical study to assess the reduction of HATT risk by using entecavir in TB patients with high baseline serum HBV DNA level, and to evaluate the risk of other treatment-related adverse events in two hospitals. From January 2012 to June 2014, subjects with culture-confirmed TB and aged from 18 to 80 with high serum HBV viral load prior to anti-tuberculous treatment will be enrolled and randomized into either study or control group. High serum HBV viral load is defined as >20,000 and >2,000 IU/mL for HBeAg-positive and HBeAg-negative subjects, respectively. In addition to standard anti-tuberculous treatment, subjects in the study group will receive entecavir (BARACLUDE®) 0.5 mg per day during anti-tuberculous treatment and for 6 months after stopping anti-tuberculous treatment. Hemogram, liver function, renal function, and serum HBV viral load will be regularly monitored to detect the development of HATT and other adverse events. In this study, HATT is defined as fulfilling anyone of the following conditions: (1) increase in serum AST and/or ALT level of >3 times upper limit of normal (ULN) with symptoms if baseline liver function is normal; (2) increase in serum AST and/or ALT level of >5 times ULN without symptoms if baseline liver function is normal; (3) increase in serum AST and/or ALT level of >2 times baseline if baseline liver function is abnormal; and (4) increase in serum total bilirubin level of > 2.5 mg/dL.

Study Type

Interventional

Enrollment (Anticipated)

50

Phase

  • 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 Contact

  • Name: Jann-Yuan Wang, Ph.D
  • Phone Number: 63565 886-2-23123456
  • Email: jywang@ntu.edu.tw

Study Contact Backup

Study Locations

  • Taiwan
      • Taipei, Taiwan, 100
        • National Taiwan University Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Jann-Yuan Wang, Ph.D.
        • Sub-Investigator:
          • Chen-Hua Liu, M.D.
        • Sub-Investigator:
          • Chin-Chung Shu, M.D.
        • Sub-Investigator:
          • Cheng-Maw Ho, M.D.
        • Sub-Investigator:
          • Jia-Horng Kao, Ph.D.
        • Sub-Investigator:
          • Li-Na Lee, Ph.D.

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

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • culture-confirmed tuberculosis
  • serology-confirmed chronic HBV infection without flare-up at present (IgM Anti-HBc-negative and either HBsAg-positive or Anti-HBc-positive)
  • high serum HBV viral load, defined as >20,000 and >2,000 IU/mL for HBeAg positive and HBeAg negative patients, respectively
  • serum AST and/or ALT level <2 times ULN
  • serum level of total bilirubin <2.0 mg/dL
  • willing to receive directly observed therapy, short course (DOTs)

Exclusion Criteria:

  • Target Disease Exceptions: human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis D virus (HDV) co-infection, multidrug-resistant tuberculosis (defined as simultaneous resistant to isoniazid and rifampin)

  • Medical History and Concurrent Diseases

    1. . ever receiving anti-viral therapy for HBV
    2. . alcoholism or presence of hepatic disease other than hepatitis B
    3. . life expectancy less than 1 year

  • Sex and Reproductive Status

    1. . Pregnancy
    2. . Breast-feeding

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: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Entecavir group
Study treatment for only treatment group: entecavir (BARACLUDE®) 0.5 mg per day during and within 6 months after anti-tuberculous treatment.
Drug: entecavir (BARACLUDE®)
entecavir 0.5 mg per day during and within 6 months after anti-tuberculous treatment
Other Names:
  • BARACLUDE®
NO_INTERVENTION: Control group
Not receiving entecavir (BARACLUDE®)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
incidence of hepatitis
Time Frame: 1 year after randomization
the reduction in the incidence of hepatitis during anti-tuberculous treatment by using entecavir in patients with high serum HBV viral load.
1 year after randomization

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
HBV viral load
Time Frame: 1 year after randomization
the reduction in HBV viral load in treatment group comparing with control group.
1 year after randomization

Collaborators and Investigators

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

Sponsor

National Taiwan University Hospital

Investigators

  • Principal Investigator: Jann-Yuan Wang, Ph.D., National Taiwan University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

December 1, 2012

Primary Completion (ANTICIPATED)

June 1, 2014

Study Completion (ANTICIPATED)

June 1, 2014

Study Registration Dates

First Submitted

May 2, 2012

First Submitted That Met QC Criteria

November 7, 2012

First Posted (ESTIMATE)

November 12, 2012

Study Record Updates

Last Update Posted (ESTIMATE)

November 12, 2012

Last Update Submitted That Met QC Criteria

November 7, 2012

Last Verified

November 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NTUH-IRB-201109046MB

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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