NCT00405301

Brief Summary

Purpose of the study is to evaluate the safety and efficacy of different re-introduction regimens in anti-TB drug induced liver damage. There is no consensus how best to treat such patients who developed drug induced liver damage.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
175

participants targeted

Target at P50-P75 for phase_4

Timeline
Completed

Started Dec 2006

Geographic Reach
1 country

2 active sites

Status
completed

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

November 27, 2006

Completed
3 days until next milestone

First Posted

Study publicly available on registry

November 30, 2006

Completed
1 day until next milestone

Study Start

First participant enrolled

December 1, 2006

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2008

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2008

Completed
Last Updated

February 16, 2012

Status Verified

February 1, 2012

Enrollment Period

1.5 years

First QC Date

November 27, 2006

Last Update Submit

February 14, 2012

Conditions

Drug Induced HepatotoxicityTuberculosis

Keywords

TuberculosisDrug Induced HepatotoxicityAnti-tuberculosis drugsIndia

Outcome Measures

Primary Outcomes (1)

  • To compare the safety of different regimens of re-introduction of anti-TB drugs in drug induced liver damage.

    24 months

Secondary Outcomes (2)

  • To study the predictors of recurrence of drug induced liver damage

    24 months

  • To study the risk factors for development of drug induced liver injury

    24 months

Study Arms (3)

Arm 1

OTHER

Arm 1: will receive Isoniazide(5mg/kg/day), Rifampicin(10mg/kg/day) and Pyrazinamide(25mg/kg/day) in full doses on day 1 and continued further

Drug: Rifampicin(max dose 10 mg/kg/day), Isoniazide (max dose 5 mg/kg/day) and Pyrazinamide (max dose 25 mg/kg/day)

Arm 2

OTHER

Arm 2 : will receive Rifampicin(10mg/kg/day) in full dose on day 1 and continued, Isoniazide(5mg/kg/day)in full dose on day 8 and continued, Pyrazinamide(25mg/kg/day)on day 15 and continued

Drug: Rifampicin(max dose 10 mg/kg/day), Isoniazide (max dose 5 mg/kg/day) and Pyrazinamide (max dose 25 mg/kg/day)

Arm 3

OTHER

Arm 3 will receive 100 mg/day of Isoniazide on day 1 which is gradually increased to maximum dose (5mg/kg/day) by day 4 and continued. Rifampicin is introduced on day 8 in a dose of 150 mg/day which is gradually increased to maximum dose (10mg/kg/day) by day 11 and continued. Pyrazinamide is introduced on day 15 in a dose of 500mg/day which is gradually increased to maximum dose (25mg/kg/day) by day 18 and continued.

Drug: Rifampicin(max dose 10 mg/kg/day), Isoniazide (max dose 5 mg/kg/day) and Pyrazinamide (max dose 25 mg/kg/day)

Interventions

Rifampicin(max dose 10 mg/kg/day), Isoniazide (max dose 5 mg/kg/day) and Pyrazinamide (max dose 25 mg/kg/day)DRUG

Patients who develop ATT drug induced hepatotoxicity will be divided into 3 arms .Arm 1,2,3 will be given drugs as described in detailed description of the title.

Arm 1Arm 2Arm 3

Eligibility Criteria

Age16 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • A rise of five times the upper limit of the normal levels (50 IU/L) of serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT)
  • A rise in the level of serum total bilirubin level \> 1.5mg/dl
  • Any increase in serum AST and or ALT above pretreatment values together with anorexia, nausea, vomiting and jaundice
  • Absence of serological evidence of infection with hepatitis viruses A,B,C,or E
  • Normalization of liver function tests after withdrawal of antituberculosis drugs For diagnosis of anti-TB drugs induced hepatitis, criteria 1 or 2 or 3 should be present along with criteria 4 and 5.

You may not qualify if:

  • Patients with serological evidence of acute viral hepatitis A,B,C,or E and carriers for HBV \& HCV
  • Age \< 15 year and age \> 65 years
  • HIV positive patients
  • Presence of chronic liver disease or cirrhosis
  • Co-administration of other potential hepatotoxic drugs (methotrexate, phenytoin, valproate)
  • Chronic alcoholics who consume \> 48 g of alcohol/day for at least one year
  • Pregnant women
  • Subjects not giving consent

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Sri Venkateswara Institute of Medical Sciences

Tirupati, Andhra Pradesh, 517507, India

Location

All India Institute of Medical Sciences

New Delhi, National Capital Territory of Delhi, 110029, India

Location

Related Publications (6)

  • Tahaoglu K, Atac G, Sevim T, Tarun T, Yazicioglu O, Horzum G, Gemci I, Ongel A, Kapakli N, Aksoy E. The management of anti-tuberculosis drug-induced hepatotoxicity. Int J Tuberc Lung Dis. 2001 Jan;5(1):65-9.

    PMID: 11263519BACKGROUND

  • Singh J, Garg PK, Tandon RK. Hepatotoxicity due to antituberculosis therapy. Clinical profile and reintroduction of therapy. J Clin Gastroenterol. 1996 Apr;22(3):211-4. doi: 10.1097/00004836-199604000-00012.

    PMID: 8724260BACKGROUND

  • Singh J, Arora A, Garg PK, Thakur VS, Pande JN, Tandon RK. Antituberculosis treatment-induced hepatotoxicity: role of predictive factors. Postgrad Med J. 1995 Jun;71(836):359-62. doi: 10.1136/pgmj.71.836.359.

    PMID: 7644398BACKGROUND

  • Sharma SK, Balamurugan A, Saha PK, Pandey RM, Mehra NK. Evaluation of clinical and immunogenetic risk factors for the development of hepatotoxicity during antituberculosis treatment. Am J Respir Crit Care Med. 2002 Oct 1;166(7):916-9. doi: 10.1164/rccm.2108091.

    PMID: 12359646BACKGROUND

  • Sharma SK. Antituberculosis drugs and hepatotoxicity. Infect Genet Evol. 2004 Jun;4(2):167-70. doi: 10.1016/j.meegid.2003.01.001. No abstract available.

    PMID: 15157635BACKGROUND

  • Sharma SK, Singla R, Sarda P, Mohan A, Makharia G, Jayaswal A, Sreenivas V, Singh S. Safety of 3 different reintroduction regimens of antituberculosis drugs after development of antituberculosis treatment-induced hepatotoxicity. Clin Infect Dis. 2010 Mar 15;50(6):833-9. doi: 10.1086/650576.

    PMID: 20156055DERIVED

MeSH Terms

Conditions

Chemical and Drug Induced Liver InjuryTuberculosis

Interventions

Pyrazinamide

Condition Hierarchy (Ancestors)

Liver DiseasesDigestive System DiseasesDrug-Related Side Effects and Adverse ReactionsChemically-Induced DisordersPoisoningMycobacterium InfectionsActinomycetales InfectionsGram-Positive Bacterial InfectionsBacterial InfectionsBacterial Infections and MycosesInfections

Intervention Hierarchy (Ancestors)

PyrazinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Officials

  • Surendra K Sharma, MD, PhD

    All India Institute of Medical Sciences

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor and Head

Study Record Dates

First Submitted

November 27, 2006

First Posted

November 30, 2006

Study Start

December 1, 2006

Primary Completion

June 1, 2008

Study Completion

December 1, 2008

Last Updated

February 16, 2012

Record last verified: 2012-02

Locations

IN(2)