Protective Effect in TB-DIH Clinical Trial
Official title:
the Safety and Effect in TB Patients With NAC
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)
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.
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Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention