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

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

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.

Study Overview

• Status: Unknown
• Conditions: Chronic Liver Disease With Tuberclosis
• Intervention / Treatment: Drug: 2HRLE/4HR; Drug: 2HRZE/4HR; Drug: 9RLE; Drug: 9HLE

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110070
      • Recruiting
      • Institute of Liver and Biliary Sciences
      • Contact: Dr Ankit Bhardwaj; Phone Number: 011-46300000; Email: bhardwaj.ankit3@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Institute of Liver and Biliary Sciences, India
• Investigators: Principal Investigator: Dr Naveen Kumar, MD, Institute of Liver and Biliary Sciences

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Anticipated): September 1, 2014
• Study Completion (Anticipated): September 1, 2014

Study Registration Dates

• First Submitted: August 30, 2012
• First Submitted That Met QC Criteria: August 30, 2012
• First Posted (Estimate): September 3, 2012

Study Record Updates

• Last Update Posted (Estimate): December 17, 2013
• Last Update Submitted That Met QC Criteria: December 16, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Liver Diseases; Tuberculosis
• Other Study ID Numbers: ILBS-ATT-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No