Back to resultsEfficacy of N-acetylcysteine to Prevent Anti-tuberculosis Drug-induced Liver Injury: A Randomized Controlled Trial
Primary Purpose
Tuberculosis, Drug Induced Liver Injury, Hepatitis
Status
Recruiting
Phase
Phase 2
Locations
Thailand
Study Type
Interventional
Intervention
N acetyl cysteine
Sponsored by
About this trial
This is an interventional prevention trial for Tuberculosis focused on measuring Tuberculosis, DILI, Anti tuberculosis
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
Sites / Locations
- Faculty of Medicine, Siriraj HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
NAC group
Non-NAC group
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05738681
Brief Title
Efficacy of N-acetylcysteine to Prevent Anti-tuberculosis Drug-induced Liver Injury: A Randomized Controlled Trial
Official Title
Efficacy of N-acetylcysteine to Prevent Anti-tuberculosis Drug-induced Liver Injury: A Randomized Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 9, 2022 (Actual)
Primary Completion Date
March 31, 2023 (Anticipated)
Study Completion Date
May 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mahidol University
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis, Drug Induced Liver Injury, Hepatitis
Keywords
Tuberculosis, DILI, Anti tuberculosis
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
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)
Allocation
Randomized
Enrollment
82 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
NAC group
Arm Type
Experimental
Arm Description
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.
Arm Title
Non-NAC group
Arm Type
No Intervention
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
N acetyl cysteine
Other Intervention Name(s)
Standard anti TB drug regimen
Intervention Description
N acetyl cysteine 1,200 mg/day for 8 weeks in NAC group
Primary Outcome Measure Information:
Title
Prevalence of hepatitis at 8 weeks
Description
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.
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
Prevalence of hepatitis among NAT2 slow acetylator patients
Description
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.
Time Frame
8 weeks
Other Pre-specified Outcome Measures:
Title
Prevalence of hepatitis at 2 weeks
Description
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.
Time Frame
2 weeks
Title
Prevalence of hepatitis at 24 weeks
Description
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.
Time Frame
24 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kittichai Samaithongcharoen, MD
Phone
0991494469
Email
pao_kitichai@hotmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Supot Supot, MD
Phone
0819134336
Email
supotgi@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Supot Nimanong, MD
Organizational Affiliation
Mahidol University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Faculty of Medicine, Siriraj Hospital
City
Bangkok
ZIP/Postal Code
10700
Country
Thailand
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kittichai Samaithongcharoen, MD
Phone
0991494469
Email
pao_kitichai@hotmail.com
First Name & Middle Initial & Last Name & Degree
Supot Nimanong, MD
Phone
0819134336
Email
supotgi@gmail.com
First Name & Middle Initial & Last Name & Degree
Supot Supot, MD
First Name & Middle Initial & Last Name & Degree
Kittichai Samaithongcharoen, MD
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Patient data may be secure and not sharing
Learn more about this trial
Efficacy of N-acetylcysteine to Prevent Anti-tuberculosis Drug-induced Liver Injury: A Randomized Controlled Trial
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