Efficacy of N-acetylcysteine to Prevent Anti-tuberculosis Drug-induced Liver Injury: A Randomized Controlled Trial

Phase 2

Recruiting

• Conditions: Tuberculosis; Drug Induced Liver Injury; Hepatitis
• Interventions: Drug: N acetyl cysteine

• Registration Number: NCT05738681
• Lead Sponsor: Mahidol University

Brief Summary

To determine the efficacy of NAC to prevent clinically significant anti-TB drugs induced liver injury (AT-DILI).

Detailed Description

Tuberculosis is one of the most important infectious diseases and treatment related hepatitis from anti-TB drug was observed for 5-28%. Slow acetylator status in the N-acetyltransferase 2 (NAT2) genotype is a significant risk factor of anti-tuberculosis drug-induced liver injury (AT-DILI). We assessed the effect of N-acetylcysteine to prevent hepatitis from anti-TB drug in Thai population.

Study Timeline

• Study First Submitted: 2022-07-11
• Study Start: 2022-09-09
• Status Verified: 2023-02
• Study First Submitted QC: 2023-02-12
• Last Update Submitted: 2023-02-12
• Study First Posted: 2023-02-22
• Last Update Posted: 2023-02-22
• Primary Completion: 2023-03-31
• Study Completion: 2023-05-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 82

Inclusion Criteria

• Newly diagnosed TB
• Received standard dose of anti-TB drugs regimen (National Tuberculosis Control Programme guideline Thailand 2018)
• Aged ≥18 years
• Informed consent

Exclusion Criteria

• Previous TB infection or MDR TB
• TB liver
• Allergy to NAC
• Abnormal baseline LFT
• (AST or ALT>2.5 times UNL, ALP> 2 times UNL, TB> 1.5 mg/dl)
• Chronic hepatitis B, C infection
• Decompensated cirrhosis
• HIV infection
• Active malignancy
• Pregnancy or lactation
• Severe co-morbidity i.e. severe heart diseases, severe lung diseases, ESRD

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NAC group	N acetyl cysteine	Tuberculosis patients who had standard regimen treatment, non-HIV, no severe co-morbidity, no chronic hepatitis B or C using NAC-long 1,200 mg/day for 8 weeks (NAC long group). Genetic test (acetylator status of NAT2), CBC, Cr, coagulogram were assessed at baseline. LFT were assessed at baseline, 2 weeks, 8 weeks and 24 weeks.

Primary Outcome Measures

Name	Time	Method
Prevalence of hepatitis at 8 weeks	8 weeks	To study efficacy of NAC to prevent anti-TB drug induced liver injury. Outcome was measured events of hepatitis occurred at 8 weeks, compared between NAC versus controlled group, presented by total number and percent.; Significant hepatitis was defined as elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) more than 5 times of baseline levels.

Secondary Outcome Measures

Name	Time	Method
Prevalence of hepatitis among NAT2 slow acetylator patients	8 weeks	To study efficacy of NAC to prevent anti-TB drug induced liver injury among NAT2 slow acetylator patients.; Outcome was measured events of hepatitis occurred at 8 weeks among NAT2 slow acetylator patients compared between NAC versus controlled group, presented by total number and percent.; Significant hepatitis was defined as elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) more than 5 times of baseline levels.

Trial Locations

Locations (1)

Faculty of Medicine, Siriraj Hospital; 🇹🇭 Bangkok, Thailand