Gene-guided N-acetyl Cysteine for Prophylaxis of Anti-tuberculous Drug- Induced Hepatitis
NCT Number: NCT06484530
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE4
Conditions: Tuberculosis (TB)|Isoniazid Toxicity|Rifampicin Toxicity|Pyrazinamide Adverse Reaction|Ethambutol Toxicity|NAT2 Slow Acetylator Status|NAT2 Rapid Acetylator Status|NAT2 Polymorphism|N-Acetylcysteine
Interventions: DRUG: N acetyl cysteine
Sponsor: Mahidol University
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 116
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: PREVENTION
Start Date: 2024-03-12
Completion Date: 2024-09-18
Locations: Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok Noi, Bangkok, 10700, Thailand

Summary:
Tuberculosis (TB) remains a significant public health concern in Thailand and globally, especially in tropical regions, with pulmonary TB being predominant. Besides affecting the lungs, TB can also impact extrapulmonary organs. Standard TB treatment involves a combination of drugs administered for at least 6 months, but it can cause adverse effects such as hepatitis. Hepatotoxicity, occurring in 20-60% of patients, is commonly linked to isoniazid, rifampicin, and pyrazinamide. Slow acetylators of the NAT2 gene are particularly susceptible. Previous research suggests N-acetylcysteine (NAC) may mitigate hepatotoxicity, especially among slow acetylators. A recent study by Kittichai Samaithongcharoen and team showed that NAC reduced hepatotoxicity incidence significantly among slow acetylators. This underscores the potential of NAC in preventing drug-induced hepatotoxicity in TB treatment, warranting further investigation against standard treatment protocols.

Primary Outcome Measures: Prevalence of hepatitis at 8 weeks, To study the efficacy of administering N-acetylcysteine (NAC) to prevent drug-induced hepatitis at 8 weeks from anti-tuberculosis medication using gene-guided therapy compared to conventional therapy.

Significant hepatitis was defined as elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) more than 5 times of baseline levels or Total bilirubin(TB) more than 2.5 milligrams per decilitre (mg/dL), 8 weeks
Secondary Outcome Measures: Prevalence of hepatitis at 2 weeks, To study the efficacy of administering N-acetylcysteine (NAC) to prevent drug-induced hepatitis at 2 weeks from anti-tuberculosis medication using gene-guided therapy compared to conventional therapy.

Significant hepatitis was defined as elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) more than 5 times of baseline levels or Total bilirubin(TB) more than 2.5 milligrams per decilitre (mg/dL), 2 weeks
Other Outcome Measures: Prevalence of hepatitis at 24 weeks, To study the efficacy of administering N-acetylcysteine (NAC) to prevent drug-induced hepatitis at 24 weeks from anti-tuberculosis medication using gene-guided therapy compared to conventional therapy.

Significant hepatitis was defined as elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) more than 5 times of baseline levels or Total bilirubin(TB) more than 2.5 milligrams per decilitre (mg/dL), 24 weeks