Study of Safety and Efficacy of Different Regimes of Reintroduction of Anti-TB Drugs in Anti-TB Drugs Induced Liver Damage

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
S.K.SHARMA, All India Institute of Medical Sciences, New Delhi
ClinicalTrials.gov Identifier:
NCT00405301
First received: November 27, 2006
Last updated: February 14, 2012
Last verified: February 2012

November 27, 2006
February 14, 2012
December 2006
June 2008   (final data collection date for primary outcome measure)
To compare the safety of different regimens of re-introduction of anti-TB drugs in drug induced liver damage. [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
To compare the safety of different regimens of re-introduction of anti-TB drugs in drug induced liver damage.
Complete list of historical versions of study NCT00405301 on ClinicalTrials.gov Archive Site
  • To study the predictors of recurrence of drug induced liver damage [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • To study the risk factors for development of drug induced liver injury [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • To study the predictors of recurrence of drug induced liver damage
  • To study the risk factors for development of drug induced liver injury
Not Provided
Not Provided
 
Study of Safety and Efficacy of Different Regimes of Reintroduction of Anti-TB Drugs in Anti-TB Drugs Induced Liver Damage
Study of Safety and Efficacy of Different Regimes of Reintroduction of Anti-TB Drugs in Antituberculosis Treatment Induced Hepatotoxicity

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.

Tuberculosis continues to be a major health problem in both the developing and developed countries because of its resurgence in the immunosuppressed patients. Short course chemotherapy containing isoniazid, rifampicin and pyrazinamide has proved to be highly effective in the treatment of tuberculosis. One of its adverse effect is liver damage which is the most common side effect leading to interruption of therapy.

There is lack of consensus guidelines for treatment of anti-TB drug induced liver damage Whether the re-introduction should take place with all the drugs given together in full doses (which reduces the chance of resistance and cost to the patient) or in a phased manner. There is lack of studies which compared different regimens of re-introduction of anti-TB drugs.

In this study, we will study three regimes of re-introduction of hepatotoxic anti-tuberculosis drugs (Rifampicin, Isoniazide, Pyrazinamide). These are potent anti-tuberculosis medications and need to be restarted in patients who developed liver toxicities attributed to these medications and became normal when these medicines were stopped. At the time of re-introduction the patients will be randomized in 3 groups.

  • First group will receive Isoniazide(5mg/kg/day), Rifampicin(10mg/kg/day) and Pyrazinamide(25mg/kg/day) in full doses on day 1 and continued further.
  • second group 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.
  • Third group 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.

All the three groups will be monitored for three months by analyzing weekly liver function tests. Any difference in the morbidity, deranged liver function or any other adverse effects will be monitored and treated appropriately.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Drug Induced Hepatotoxicity
  • Tuberculosis
Drug: Rifampicin(max dose 10 mg/kg/day), Isoniazide (max dose 5 mg/kg/day) and Pyrazinamide (max dose 25 mg/kg/day)
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 1
    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
    Intervention: 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
    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
    Intervention: 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
    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.
    Intervention: Drug: Rifampicin(max dose 10 mg/kg/day), Isoniazide (max dose 5 mg/kg/day) and Pyrazinamide (max dose 25 mg/kg/day)

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
175
December 2008
June 2008   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
Both
16 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
India
 
NCT00405301
AIIMS/MED/2006/10
No
S.K.SHARMA, All India Institute of Medical Sciences, New Delhi
All India Institute of Medical Sciences, New Delhi
Not Provided
Principal Investigator: Surendra K Sharma, MD, PhD All India Institute of Medical Sciences, New Delhi
All India Institute of Medical Sciences, New Delhi
February 2012

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