Clinical trial NCT02889757: The Protective Effect for Liver Organ in Patients With Anti-TB Drugs Using of Acetylcysteine (NAC)
Official title: the Safety and Effect in TB Patients With NAC
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Protective Effect in TB-DIH
TB-DIH Means: Drug Induced Liver Function Abnormalities
Keywords: tuberculosis
acetylcysteine
hepatotoxicity
Lead sponsor: Far Eastern Memorial Hospital
Sponsor class: OTHER
First posted: 2016-09-07
Enrollment: 400
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: the incidence of DIH
timeFrame: during the 6 months treatment
Secondary outcomes:
measure: the incidence for other side effects
timeFrame: 6 months
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: Far Eastern Memorial Hospital
Study officials:
References: