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

Phase 4

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

• Registration Number: NCT02889757
• Lead Sponsor: Far Eastern Memorial Hospital

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.

Study Timeline

• Study First Submitted: 2016-08-31
• Status Verified: 2016-09
• Study First Submitted QC: 2016-09-06
• Study First Posted: 2016-09-07
• Last Update Submitted: 2016-09-09
• Last Update Posted: 2016-09-13
• Study Start: 2017-01
• Primary Completion: 2018-12
• Study Completion: 2019-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 400

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
NAC 2400 mg	Acteylcysteine	patients with add NAC (600) 2# bid use per day during the study period
NAC 0 mg	Acteylcysteine	patients with add NAC (600) 0# (placebo) use per day during the study period
NAC 1200 mg	Acteylcysteine	patients with add NAC (600) 1# bid use per day during the study period

Primary Outcome Measures

Name	Time	Method
the incidence of DIH	during the 6 months treatment	the rate for

Secondary Outcome Measures

Name	Time	Method
the incidence for other side effects	6 months	side effects including GI upset, blurred vision, neuropathy, renal organ damage

Trial Locations

Locations (1)

Far Eastern Memorial Hospital; 🇨🇳 Taipei, Taiwan