Reintroduction Regimens After Hepatitis During Anti-tuberculosis Treatment

Different Reintroduction Regimens of Antituberculosis Drugs After Development of Hepatitis During Anti-tuberculosis Treatment

Despite the availability of effective anti-tuberculosis agents that exist to treat this illness, hepatotoxicity during first-line drugs anti-tuberculosis medications (ATT) such as isoniazid (INH), rifampin (RIF), and pyrazinamide (PZA) is not uncommon and limit their use. There is no consensus on method of the reintroduction of anti-TB medications. The risk of reintroducing of a anti-TB medications could be hazardous. There are several differences between the guidelines from the ATS, BTS and the Task Force of the European Respiratory Society, the WHO and the International Union Against Tuberculosis and Lung Disease about the methods of reintroducing of anti-TB medications.

The investigators plan to do a prospective study to evaluate the outcome and safety of reintroduction of anti-TB medications after resolution of hepatitis during anti-TB treatment among TB patients in the investigators hospital.

Study Overview

• Status: Unknown
• Conditions: Hepatitis; Tuberculosis, Pulmonary
• Intervention / Treatment: Drug: isoniazid, rifampin, pyrazinamide

Detailed Description

Tuberculosis (TB) remains a leading health problem in both developing and developed countries. Despite the availability of effective chemotherapeutic agents that exist to treat this illness, hepatotoxicity during first-line drugs anti-tuberculosis medications (ATT) such as isoniazid (INH), rifampin (RIF), and pyrazinamide (PZA) is not uncommon and limit their use. In the case of confirmed moderate or severe drug-induced hepatotoxicity, treatment should be interrupted and reintroduced after the hepatotoxicity has resolved.

There is no consensus on method of the reintroduction of anti-TB medications. The risk of reintroducing of a anti-TB medications could be hazardous. There are several differences between the guidelines from the ATS, BTS and the Task Force of the European Respiratory Society, the WHO and the International Union Against Tuberculosis and Lung Disease about the methods of reintroducing of anti-TB medications.

We plan to do a prospective study to evaluate the outcome and safety of reintroduction of anti-TB medications after resolution of hepatitis during anti-TB treatment among TB patients in our hospital.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jann-Yuan Wang, MD; Phone Number: 886-2-3123456; Email: jywang@ntu.edu.tw

Study Locations

• Taiwan
  • Tainan, Taiwan
    • Recruiting
    • Chest Hospital
    • Contact: Jung-Yien Chien; Phone Number: 3206 886-6-2705911; Email: jychien@ntu.edu.tw
  • Taipei, Taiwan
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Jann-Yuan Wang; Phone Number: 23123456; Email: jywang@ntu.edu.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Hepatitis during anti-tuberculosis treatment
• Hold RMP, INH and PZA after hepatitis
• Age >= 18 years old
• HIV(-)
• T-bilirubin < 2.5 mg/dL
• No allergy to RMP, INH and PZA

Exclusion Criteria:

• Liver cirrhosis, child B or C
• Pregnancy and breast feeding
• Life expectation < 1 year

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Standard rechallenge, Slow rechallenge	Drug: isoniazid, rifampin, pyrazinamide; rechallenge of isoniazid (INH), rifampin (RIF), and pyrazinamide (PZA) aftr recovery from hepatitis; Other Names: PZA; INH; RIF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The duration needed for successfully rechallenge anti-tuberculosis treatment	participants will be followed for the duration of hospital stay, an expected average of 5 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of participants with recurrence of hepatitis	participants will be followed for the duration of hospital stay, an expected average of 5 weeks

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Jann-Yuan Wang, National Taiwan University

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Anticipated): December 1, 2013
• Study Completion (Anticipated): December 1, 2015

Study Registration Dates

• First Submitted: July 5, 2011
• First Submitted That Met QC Criteria: July 14, 2011
• First Posted (Estimate): July 15, 2011

Study Record Updates

• Last Update Posted (Estimate): December 27, 2012
• Last Update Submitted That Met QC Criteria: December 26, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Liver Diseases; Hepatitis, Viral, Human; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Enterovirus Infections; Picornaviridae Infections; Mycobacterium Infections; Hepatitis; Hepatitis A; Tuberculosis; Tuberculosis, Pulmonary; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; Anti-Bacterial Agents; Leprostatic Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Fatty Acid Synthesis Inhibitors; Rifampin; Isoniazid; Pyrazinamide
• Other Study ID Numbers: 201010025M