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

This study is not yet open for participant recruitment.
Verified November 2012 by National Taiwan University Hospital
Sponsor:
Information provided by (Responsible Party):
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT01724723
First received: May 2, 2012
Last updated: November 7, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Hepatitis
Tuberculosis
hepatitisB
Drug: entecavir (BARACLUDE®)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Prophylactic Use of Entecavir to Reduce Hepatitis Flare in Highly Viremic HBV Patients With Active Tuberculosis Receiving Anti-tuberculous Treatment

Resource links provided by NLM:


Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures:
  • incidence of hepatitis [ Time Frame: 1 year after randomization ] [ Designated as safety issue: No ]
    the reduction in the incidence of hepatitis during anti-tuberculous treatment by using entecavir in patients with high serum HBV viral load.


Secondary Outcome Measures:
  • HBV viral load [ Time Frame: 1 year after randomization ] [ Designated as safety issue: No ]
    the reduction in HBV viral load in treatment group comparing with control group.


Estimated Enrollment: 50
Study Start Date: December 2012
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: BARACLUDE®
No Intervention: Control group
Not receiving entecavir (BARACLUDE®)

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01724723

Contacts
Contact: Jann-Yuan Wang, Ph.D 886-2-23123456 ext 63565 jywang@ntu.edu.tw
Contact: Chin-Chugn Shu, M.D 886-2-23123456 ext 62905 stree139@ntu.edu.tw

Locations
Taiwan
National Taiwan University Hospital Not yet recruiting
Taipei, Taiwan, 100
Contact: Jann-Yuan Wang, Ph.D.    886-2-23123456 ext 63565    jywang@ntu.edu.tw   
Contact: Chin-Chung Shu, M.D.    886-2-23123456 ext 62905    stree139@ntu.edu.tw   
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.         
Sponsors and Collaborators
National Taiwan University Hospital
Investigators
Principal Investigator: Jann-Yuan Wang, Ph.D. National Taiwan University Hospital
  More Information

Publications:

Responsible Party: National Taiwan University Hospital, Physician
ClinicalTrials.gov Identifier: NCT01724723     History of Changes
Other Study ID Numbers: NTUH-IRB-201109046MB
Study First Received: May 2, 2012
Last Updated: November 7, 2012
Health Authority: Taiwan: Department of Health

Keywords provided by National Taiwan University Hospital:
hepatitis during anti-tuberculous treatment
tuberculosis
hepatitis B virus
viral load
entecavir

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Tuberculosis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Entecavir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014