the Safety and Effect in TB Patients With NAC
试验速览
- 阶段
- 4 期
- 入组人数
- 400
- 试验地点
- 1
- 主要终点
- the incidence of DIH
研究概览
简要总结
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)
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •new diagnosed to have tuberculosis
- •age >20 years -
排除标准
- •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
研究组 & 干预措施
NAC 2400 mg
patients with add NAC (600) 2# bid use per day during the study period
干预措施: Acteylcysteine (Drug)
NAC 1200 mg
patients with add NAC (600) 1# bid use per day during the study period
干预措施: Acteylcysteine (Drug)
NAC 0 mg
patients with add NAC (600) 0# (placebo) use per day during the study period
干预措施: Acteylcysteine (Drug)
结局指标
主要结局
the incidence of DIH
时间窗: during the 6 months treatment
the rate for
次要结局
- the incidence for other side effects(6 months)
研究者
Shih-Lung Cheng
Associate Professor
Far Eastern Memorial Hospital