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

Sponsor
Mahidol University (Other)
Overall Status
Recruiting
CT.gov ID
NCT05738681
Collaborator
(none)
82
Enrollment
1
Location
2
Arms
8.7
Anticipated Duration (Months)
9.5
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
  • Drug: N acetyl cysteine
 Phase 2/Phase 3

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 Design

Study Type:
Interventional
Anticipated Enrollment :
82 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
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.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)
Primary Purpose:
Prevention
Official Title:
Efficacy of N-acetylcysteine to Prevent Anti-tuberculosis Drug-induced Liver Injury: A Randomized Controlled Trial
Actual Study Start Date :
Sep 9, 2022
Anticipated Primary Completion Date :
Mar 31, 2023
Anticipated Study Completion Date :
May 31, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: NAC group

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
N acetyl cysteine 1,200 mg/day for 8 weeks in NAC group
Other Names:
  • Standard anti TB drug regimen

    		•
    No Intervention: Non-NAC group

    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.

    Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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 Outcome Measures

    1. 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.

    2. 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 99 Years
    Sexes Eligible for Study:
    All
    Accepts 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Faculty of Medicine, Siriraj Hospital Bangkok Thailand 10700

    Sponsors and Collaborators

    • Mahidol University

    Investigators

    • Principal Investigator: Supot Nimanong, MD, Mahidol University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Watcharasak Chotiyaputta, Associate professor, Faculty of Medicine, Siriraj Hospital Affiliation: Mahidol University, Mahidol University
    ClinicalTrials.gov Identifier:
    NCT05738681
    Other Study ID Numbers:
    • Si 1052/2020
    First Posted:
    Feb 22, 2023
    Last Update Posted:
    Feb 22, 2023
    Last Verified:
    Feb 1, 2023
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Watcharasak Chotiyaputta, Associate professor, Faculty of Medicine, Siriraj Hospital Affiliation: Mahidol University, Mahidol University
    Tuberculosis
    DILI
    Anti tuberculosis
    Additional relevant MeSH terms:
    Tuberculosis
    Chemical and Drug Induced Liver Injury
    Wounds and Injuries
    Acetylcysteine
    N-monoacetylcystine

    Study Results

    No Results Posted as of Feb 22, 2023