NCT01724723

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
50

participants targeted

Target at P25-P50 for phase_4

Timeline
Completed

Started Dec 2012

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 2, 2012

Completed
6 months until next milestone

First Posted

Study publicly available on registry

November 12, 2012

Completed
19 days until next milestone

Study Start

First participant enrolled

December 1, 2012

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2014

Completed
Last Updated

November 12, 2012

Status Verified

November 1, 2012

Enrollment Period

1.5 years

First QC Date

May 2, 2012

Last Update Submit

November 7, 2012

Conditions

HepatitisTuberculosishepatitisB

Keywords

hepatitis during anti-tuberculous treatmenttuberculosishepatitis B virusviral loadentecavir

Outcome Measures

Primary Outcomes (1)

  • incidence of hepatitis

    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 Outcomes (1)

  • HBV viral load

    1 year after randomization

Study Arms (2)

Entecavir group

EXPERIMENTAL

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®)

Control group

NO INTERVENTION

Not receiving entecavir (BARACLUDE®)

Interventions

entecavir (BARACLUDE®)DRUG

entecavir 0.5 mg per day during and within 6 months after anti-tuberculous treatment

Also known as: BARACLUDE®
Entecavir group

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)

You may not qualify if:

  • 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
  • ever receiving anti-viral therapy for HBV
  • alcoholism or presence of hepatic disease other than hepatitis B
  • life expectancy less than 1 year
  • Sex and Reproductive Status
  • Pregnancy
  • Breast-feeding

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Related Publications (16)

  • Albert RK, Iseman M, Sbarbaro JA, Stage A, Pierson DJ. Monitoring patients with tuberculosis for failure during and after treatment. Am Rev Respir Dis. 1976 Dec;114(6):1051-60. doi: 10.1164/arrd.1976.114.6.1051.

    PMID: 827221BACKGROUND

  • American Thoracic Society; Centers for Disease Control and Prevention; Infectious Diseases Society of America. American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: controlling tuberculosis in the United States. Am J Respir Crit Care Med. 2005 Nov 1;172(9):1169-227. doi: 10.1164/rccm.2508001.

    PMID: 16249321BACKGROUND

  • Saukkonen JJ, Cohn DL, Jasmer RM, Schenker S, Jereb JA, Nolan CM, Peloquin CA, Gordin FM, Nunes D, Strader DB, Bernardo J, Venkataramanan R, Sterling TR; ATS (American Thoracic Society) Hepatotoxicity of Antituberculosis Therapy Subcommittee. An official ATS statement: hepatotoxicity of antituberculosis therapy. Am J Respir Crit Care Med. 2006 Oct 15;174(8):935-52. doi: 10.1164/rccm.200510-1666ST.

    PMID: 17021358BACKGROUND

  • American Thoracic Society; CDC; Infectious Diseases Society of America. Treatment of tuberculosis. MMWR Recomm Rep. 2003 Jun 20;52(RR-11):1-77. No abstract available.

    PMID: 12836625BACKGROUND

  • Lee BH, Koh WJ, Choi MS, Suh GY, Chung MP, Kim H, Kwon OJ. Inactive hepatitis B surface antigen carrier state and hepatotoxicity during antituberculosis chemotherapy. Chest. 2005 Apr;127(4):1304-11. doi: 10.1378/chest.127.4.1304.

    PMID: 15821209BACKGROUND

  • Wong WM, Wu PC, Yuen MF, Cheng CC, Yew WW, Wong PC, Tam CM, Leung CC, Lai CL. Antituberculosis drug-related liver dysfunction in chronic hepatitis B infection. Hepatology. 2000 Jan;31(1):201-6. doi: 10.1002/hep.510310129.

    PMID: 10613746BACKGROUND

  • Ungo JR, Jones D, Ashkin D, Hollender ES, Bernstein D, Albanese AP, Pitchenik AE. Antituberculosis drug-induced hepatotoxicity. The role of hepatitis C virus and the human immunodeficiency virus. Am J Respir Crit Care Med. 1998 Jun;157(6 Pt 1):1871-6. doi: 10.1164/ajrccm.157.6.9711039.

    PMID: 9620920BACKGROUND

  • Ozick LA, Jacob L, Comer GM, Lee TP, Ben-Zvi J, Donelson SS, Felton CP. Hepatotoxicity from isoniazid and rifampin in inner-city AIDS patients. Am J Gastroenterol. 1995 Nov;90(11):1978-80.

    PMID: 7485004BACKGROUND

  • Wang JY, Lee LN, Yu CJ, Chien YJ, Yang PC; Tami Group. Factors influencing time to smear conversion in patients with smear-positive pulmonary tuberculosis. Respirology. 2009 Sep;14(7):1012-9. doi: 10.1111/j.1440-1843.2009.01598.x. Epub 2009 Jul 30.

    PMID: 19659516BACKGROUND

  • Shakya R, Rao BS, Shrestha B. Incidence of hepatotoxicity due to antitubercular medicines and assessment of risk factors. Ann Pharmacother. 2004 Jun;38(6):1074-9. doi: 10.1345/aph.1D525. Epub 2004 Apr 30.

    PMID: 15122004BACKGROUND

  • Chen CJ, Yang HI. Natural history of chronic hepatitis B REVEALed. J Gastroenterol Hepatol. 2011 Apr;26(4):628-38. doi: 10.1111/j.1440-1746.2011.06695.x.

    PMID: 21323729BACKGROUND

  • Lee MH, Yang HI, Jen CL, Lu SN, Yeh SH, Liu CJ, You SL, Sun CA, Wang LY, Chen WJ, Chen CJ; R.E.V.E.A.L.-HCV Study Group. Community and personal risk factors for hepatitis C virus infection: a survey of 23,820 residents in Taiwan in 1991-2. Gut. 2011 May;60(5):688-94. doi: 10.1136/gut.2010.220889. Epub 2010 Nov 10.

    PMID: 21068131BACKGROUND

  • Wang JY, Liu CH, Hu FC, Chang HC, Liu JL, Chen JM, Yu CJ, Lee LN, Kao JH, Yang PC. Risk factors of hepatitis during anti-tuberculous treatment and implications of hepatitis virus load. J Infect. 2011 Jun;62(6):448-55. doi: 10.1016/j.jinf.2011.04.005. Epub 2011 Apr 28.

    PMID: 21570123BACKGROUND

  • Huang YS, Chern HD, Su WJ, Wu JC, Chang SC, Chiang CH, Chang FY, Lee SD. Cytochrome P450 2E1 genotype and the susceptibility to antituberculosis drug-induced hepatitis. Hepatology. 2003 Apr;37(4):924-30. doi: 10.1053/jhep.2003.50144.

    PMID: 12668988BACKGROUND

  • Lee HC, Suh DJ, Ryu SH, Kim H, Shin JW, Lim YS, Chung YH, Lee YS. Quantitative polymerase chain reaction assay for serum hepatitis B virus DNA as a predictive factor for post-treatment relapse after lamivudine induced hepatitis B e antigen loss or seroconversion. Gut. 2003 Dec;52(12):1779-83. doi: 10.1136/gut.52.12.1779.

    PMID: 14633962BACKGROUND

  • Black M, Mitchell JR, Zimmerman HJ, Ishak KG, Epler GR. Isoniazid-associated hepatitis in 114 patients. Gastroenterology. 1975 Aug;69(2):289-302.

    PMID: 1150039BACKGROUND

MeSH Terms

Conditions

HepatitisTuberculosisHepatitis B

Interventions

entecavir

Condition Hierarchy (Ancestors)

Liver DiseasesDigestive System DiseasesMycobacterium InfectionsActinomycetales InfectionsGram-Positive Bacterial InfectionsBacterial InfectionsBacterial Infections and MycosesInfectionsBlood-Borne InfectionsCommunicable DiseasesHepadnaviridae InfectionsDNA Virus InfectionsVirus DiseasesHepatitis, Viral, Human

Study Officials

  • Jann-Yuan Wang, Ph.D.

    National Taiwan University Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Jann-Yuan Wang, Ph.D

CONTACT

886-2-23123456jywang@ntu.edu.tw

Chin-Chugn Shu, M.D

CONTACT

886-2-23123456stree139@ntu.edu.tw

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Physician

Study Record Dates

First Submitted

May 2, 2012

First Posted

November 12, 2012

Study Start

December 1, 2012

Primary Completion

June 1, 2014

Study Completion

June 1, 2014

Last Updated

November 12, 2012

Record last verified: 2012-11

Locations

TW(1)