The Protective Effect for Liver Organ in Patients With Anti-TB Drugs Using of Acetylcysteine (NAC)

NCT ID: NCT02889757

Last Updated: 2016-09-13

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-31
• Study Completion Date: 2019-06-30

Brief Summary

Animal studies have shown that INH-RIF-induced oxidative injury can be prevented by supporting the cellular antioxidant defense mechanism by N-acetylcysteine (NAC). However, there are few published data and large sample sizes regarding the protective effect of NAC against hepatotoxicty induced by anti-TB drugs in humans, to our knowledge.

Therefore, the investigators designed a clinical trial with the aim to see whether NAC could protect against anti-TB drug-induced hepatotoxicity (DIH)

Detailed Description

Isoniazid (INH), rifampicin (RIF), and pyrazinamide (PZA), the first-line drugs used for tuberculosis (TB) chemotherapy, are associated with hepatotoxicity. A high rate of hepatotoxicity has been reported in some developing countries compared with advanced countries with a similar dose schedule. Sharifzadeh et al. reported an incidence of 27.7% in Iran. The reasons for this higher rate of hepatotoxicity are not completely clear. Ethnic variations, advanced age, female sex, alcoholism, underlying liver disease, acetylator phenotype, hepatitis B and C virus, HIV infection, extensive pulmonary parenchymal disease, and hypoalbuminemia have been observed to be the risk factors for the development of drug-induced hepatotoxicity (DIH) because of anti-TB treatment.

The mechanism of DIH induced by anti-TB treatment is not yet fully understood. Sodhi et al. proposed oxidative stress as one of the likely mechanisms for INH-RIF-induced hepatic injury. It is well established that by augmenting a cellular antioxidative defense system, especially nonprotein thiols, that is, glutathione (GSH), cells can be protected against oxidative injuries produced by various drugs and chemicals.

The study will be performed with randomized trial for assessment and protective effects over liver function in patients receiving anti-TB agents and using NAC.

Conditions

Protective Effect in TB-DIH; TB-DIH Means: Drug Induced Liver Function Abnormalities

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

NAC 1200 mg

patients with add NAC (600) 1# bid use per day during the study period

Group Type: EXPERIMENTAL

Acteylcysteine

Intervention Type: DRUG

randomized into three arms

NAC 2400 mg

patients with add NAC (600) 2# bid use per day during the study period

Group Type: EXPERIMENTAL

Acteylcysteine

Intervention Type: DRUG

randomized into three arms

NAC 0 mg

patients with add NAC (600) 0# (placebo) use per day during the study period

Group Type: PLACEBO_COMPARATOR

Acteylcysteine

Intervention Type: DRUG

randomized into three arms

Interventions

Acteylcysteine

randomized into three arms

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. new diagnosed to have tuberculosis

2. age >20 years -

Exclusion Criteria

1. acute hepatitis in a previous one year

2. TB drugs induced urticaria or Steven-Johnson syndrome

3. life less than one year due to advanced cancer status

4. non-tuberculosis mycobacteria，NTM patients

5. HIV patients

6. patients can not cooperate

7. Allergic reaction for NAC

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Far Eastern Memorial Hospital

OTHER

Sponsor Role: lead

Responsible Party

Shih-Lung Cheng

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Far Eastern Memorial Hospital

Taipei, , Taiwan

Countries

Taiwan

Other Identifiers

T-6621

Identifier Type: -

Identifier Source: org_study_id