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

Far Eastern Memorial Hospital

Status and phase: Unknown; Phase 4

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

Treatments: Drug: Acteylcysteine

Study type: Interventional

Funder types: Other

Identifiers

NCT02889757

T-6621

Details and patient eligibility

About

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)

Full 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.

Enrollment: 400 estimated patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Double Blind

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400 participants in 3 patient groups, including a placebo group

NAC 1200 mg

Experimental group

Description:

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

Treatment:

Drug: Acteylcysteine

NAC 2400 mg

Experimental group

Description:

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

Treatment:

Drug: Acteylcysteine

NAC 0 mg

Placebo Comparator group

Description:

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

Treatment:

Drug: Acteylcysteine