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

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ClinicalTrials.gov Identifier: NCT01724723
Recruitment Status : Unknown
Verified November 2012 by National Taiwan University Hospital.
Recruitment status was:  Not yet recruiting
First Posted : November 12, 2012
Last Update Posted : November 12, 2012
Sponsor:
Information provided by (Responsible Party):
National Taiwan University Hospital

Tracking Information
First Submitted Date  ICMJE May 2, 2012
First Posted Date  ICMJE November 12, 2012
Last Update Posted Date November 12, 2012
Study Start Date  ICMJE December 2012
Estimated Primary Completion Date June 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 7, 2012)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: November 7, 2012)
HBV viral load [ Time Frame: 1 year after randomization ]
the reduction in HBV viral load in treatment group comparing with control group.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Using Entecavir to Reduce Hepatitis in Highly Viremic HBV Patients During Anti-tuberculous Treatment
Official Title  ICMJE Prophylactic Use of Entecavir to Reduce Hepatitis Flare in Highly Viremic HBV Patients With Active Tuberculosis Receiving Anti-tuberculous Treatment
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • Hepatitis
  • Tuberculosis
  • hepatitisB
Intervention  ICMJE Drug: entecavir (BARACLUDE®)
entecavir 0.5 mg per day during and within 6 months after anti-tuberculous treatment
Other Name: BARACLUDE®
Study Arms  ICMJE
  • 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.
    Intervention: Drug: entecavir (BARACLUDE®)
  • No Intervention: Control group
    Not receiving entecavir (BARACLUDE®)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: November 7, 2012)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2014
Estimated Primary Completion Date June 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Taiwan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01724723
Other Study ID Numbers  ICMJE NTUH-IRB-201109046MB
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Taiwan University Hospital
Study Sponsor  ICMJE National Taiwan University Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jann-Yuan Wang, Ph.D. National Taiwan University Hospital
PRS Account National Taiwan University Hospital
Verification Date November 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP