Study of Safety and Efficacy of Different Regimes of Reintroduction of Anti-TB Drugs in Anti-TB Drugs Induced Liver Damage
Condition: Drug Induced Hepatotoxicity; Tuberculosis
MeSH terms: Tuberculosis
Study type: Interventional
Phase: Phase 4

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.
    

Detailed description: 
      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.
    

Intervention name(s): Rifampicin(max dose 10 mg/kg/day), Isoniazide (max dose 5 mg/kg/day) and Pyrazinamide (max dose 25 mg/kg/day)
Intervention type(s): Drug
Intervention description(s): 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.
Intervention MeSH terms: Rifampin; Pyrazinamide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Tuberculosis; Drug Induced Hepatotoxicity; Anti-tuberculosis drugs; India