Tuberculosis, Drug Induced Liver Injury, Hepatitis
Conditions
Keywords
Tuberculosis, DILI, Anti tuberculosis
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.
Interventions
N acetyl cysteine 1,200 mg/day for 8 weeks in NAC group
Sponsors
Mahidol University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Prevalence of hepatitis at 2 weeks | 2 weeks | Outcome was measured events of hepatitis occurred at 2 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. |
| Prevalence of hepatitis at 24 weeks | 24 weeks | Outcome was measured events of hepatitis occurred at 24 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. |
Countries
Thailand
Contacts
Primary ContactKittichai Samaithongcharoen, MD
Backup ContactSupot Supot, MD
Outcome results
None listed