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

Study Overview
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Brief Summary
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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
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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.

Official Title
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the Safety and Effect in TB Patients With NAC

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

Intervention / Treatment
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* Drug: Acteylcysteine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: new diagnosed to have tuberculosis age >20 years - Exclusion Criteria: acute hepatitis in a previous one year TB drugs induced urticaria or Steven-Johnson syndrome life less than one year due to advanced cancer status non-tuberculosis mycobacteria，NTM patients HIV patients patients can not cooperate Allergic reaction for NAC

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NAC 1200 mg<br>patients with add NAC (600) 1# bid use per day during the study period | Drug: Acteylcysteine<br>* randomized into three arms<br>|
| Experimental: NAC 2400 mg<br>patients with add NAC (600) 2# bid use per day during the study period | Drug: Acteylcysteine<br>* randomized into three arms<br>|
| Placebo Comparator: NAC 0 mg<br>patients with add NAC (600) 0# (placebo) use per day during the study period | Drug: Acteylcysteine<br>* randomized into three arms<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the incidence of DIH | the rate for | during the 6 months treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the incidence for other side effects | side effects including GI upset, blurred vision, neuropathy, renal organ damage | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tuberculosis, acetylcysteine, hepatotoxicity