Efficacy and Safety of Modified Anti-tubercular Regimens in Treatment of Tuberculosis in Patients With Underlying Compensated and Decompensated Chronic Liver Disease

Study Overview
=================
Brief Summary
-----------------
During the Study: Subject is required to visit every week for the first 2 months and then every month till completion of study or as and when required The usual symptomatic and supportive treatment of Chronic Liver Disease, including use of antiviral, will be given to all patients. Effort will be made to avoid use of other hepatotoxic drug(s) during Anti-Tubercular Treatment. Liver function tests (LFT) will be done weekly during first 2 months then at one month interval or as when required. The treatment efficacy of Anti-Tubercular Treatment (ATT) will be made on the basis of clinical, biochemical, microbiological and imaging parameters at months 2, 4, 7 and 9. Patients not improving at 4 weeks after initiation of treatment will be shifted to alternative regimens and will be excluded from the study.

Official Title
-----------------
Study of Efficacy and Safety of Modified Anti-tubercular Regimens in Treatment of Tuberculosis in Patients With Underlying Compensated and Decompensated Chronic Liver Disease

Conditions
-----------------
Chronic Liver Disease With Tuberclosis

Intervention / Treatment
-----------------
* Drug: 2HRZE/4HR
* Drug: 2HRLE/4HR
* Drug: 9HLE
* Drug: 9RLE


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males or Females subjects aged 18-75 years. Subjects with chronic liver disease (cirrhosis) Pulmonary or extra-pulmonary tuberculosis. Serum ALT≤5times upper limit and serum bilirubin ≤3 mg/dl. consent and willingness to follow-up Exclusion Criteria: Serum ALT>5times upper limit and serum bilirubin >3 mg/dl. Renal failure (serum creatinine>2mg/dl). Presence of hepatocellular carcinoma Alcoholic cirrhotic who continue to drink alcohol. Prior history of ATT (ANTI TUBERCULAR TREATMENT) with documented hepatotoxicity. Known hypersensitivity to levofloxacin, other quinolones

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2HRZE/4HR<br>Isoniazid + Rifampicin+Pyrazinamide+Ethambutol for initial 2 months floolowed by Isoniazid + Rifampicin for next 4 months | Drug: 2HRLE/4HR<br>* Isoniazid + Rifampicin+ Levofloxacin+Ethambutol for initial 2 months followed by Isonizid + Rifampicin for next 4 months<br>|
| Active Comparator: 2HRLE/4HR<br>Isoniazid + Rifampicin+ Levofloxacin+Ethambutol for initial 2 months followed by Isonizid + Rifampicin for next 4 months | Drug: 2HRZE/4HR<br>* Isoniazid + Rifampicin+Pyrazinamide+Ethambutol for initial 2 months floolowed by Isoniazid + Rifampicin for next 4 months<br>|
| Experimental: 9HLE<br>Isoniazid+ Levofloxacin+ Ethambutol for 9 months | Drug: 9RLE<br>* Rifampicin + Levofloxacin+ Ethambutol for 9 months<br>|
| Active Comparator: 9RLE<br>Rifampicin + Levofloxacin+ Ethambutol for 9 months | Drug: 9HLE<br>* Isoniazid+ Levofloxacin+ Ethambutol for 9 months<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Successful completion of modified ATT (ANTI TUBERCULAR TREATMENT) regimen. |  | 6 and 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Worsening of CTP (CHILD TURCOTTE PUGH) score to ≥10 for patients with compensated cirrhosis, |  | 6 and 9 months | 
| Failure to re-institute the assigned ATT (ANTI TUBERCULAR TREATMENT) regimen after development of an episode of hepatotoxicity. (I.e. second episode of hepatotoxicity. |  |  | 
| Survival |  | 6 and 9 months |