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

Study Overview
=================
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.

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

Conditions
-----------------
Tuberculosis, Drug Induced Liver Injury, Hepatitis

Intervention / Treatment
-----------------
* Drug: N acetyl cysteine


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Tuberculosis patients who had standard regimen treatment, non-HIV, no severe co-morbidity, no chronic hepatitis B or C were randomized to using NAC-long 1,200 mg/day for 8 weeks (NAC long group) or using anti-TB alone (non-NAC group). Genetic test, CBC, Cr, coagulogram were assessed at baseline. LFT were assessed at baseline, 2 weeks, 8 weeks and 24 weeks.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NAC group<br>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. | Drug: N acetyl cysteine<br>* N acetyl cysteine 1,200 mg/day for 8 weeks in NAC group<br>* Other names: Standard anti TB drug regimen;|
| No Intervention: Non-NAC group<br>Tuberculosis patients who had standard regimen treatment, non-HIV, no severe co-morbidity, no chronic hepatitis B or C were using anti-TB alone (non-NAC 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. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of hepatitis at 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. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of hepatitis among NAT2 slow acetylator patients | 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. | 8 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Tuberculosis, DILI, Anti tuberculosis