Protective Effect in TB-DIH, TB-DIH Means: Drug Induced Liver Function Abnormalities
Conditions
Keywords
tuberculosis, acetylcysteine, hepatotoxicity
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.
Interventions
DRUGActeylcysteine
randomized into three arms
Sponsors
Far Eastern Memorial Hospital
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| the incidence of DIH | during the 6 months treatment | the rate for |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| the incidence for other side effects | 6 months | side effects including GI upset, blurred vision, neuropathy, renal organ damage |
Countries
Taiwan
Outcome results
None listed