Drug Induced Liver InjuryPhase 1NCT07058090
Comparison of the Outcome of Treatment With Silymarin or N-Aceylcysteine in Patients Taking Anti-Tuberculous Drugs for Tuberculosis at a Tertiary Care Hospital , Karachi
A Phase 1 study testing Silymarin 420 mg, N Acetyl Cysteine and Rifampicin (RMP) Ethambutol (E) Isoniazid (H) Pyrazinamid (Z) in people with Drug Induced Liver Injury and Tuberculosis (TB), run by Liaquat National Hospital & Medical College.
Trial summary
OBJECTIVE : To compare the outcome of treatment with silymarin or N-acetyl cysteine in patients taking anti-tuberculous drugs for tuberculosis at Tertiary Care Hospital, Karachi. Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Drug Induced Liver Injury, Tuberculosis (TB)
- What is being tested?
- Silymarin 420 mg, N Acetyl Cysteine and Rifampicin (RMP) Ethambutol (E) Isoniazid (H) Pyrazinamid (Z)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 410 participants
- Where
- No sites listed yet
- Study dates
- Jul 2025to May 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients presenting with tuberculosis and previously not on any anti-tuberculous drugs, between 40-80 years of age
- either gender.
Who cannot join
- History of malignancy.
- Patients with history of seropositive, seronegative, connective tissue disorder or vasculitis, congestive cardiac failure.
- Patients with history of alcohol use.
- Discontinuation of drug due to other adverse effects except hepatotoxicity.
- Inadequate date of laboratory testing at baseline or 2 to 4 weeks after treatment initiation.
- Cases with human immunodeficiency virus (HIV) co-infection, viral hepatitis, or suspected mal absorption (e.g., gastrointestinal disease or diarrhea).
- Chronic liver disease, COPD, asthma, myocardial infarction, chronic kidney disease and stroke.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
OBJECTIVE : To compare the outcome of treatment with silymarin or N-acetyl cysteine in patients taking anti-tuberculous drugs for tuberculosis at Tertiary Care Hospital, Karachi.
SAMPLE SELECTION : Patients presenting with tuberculosis previously not on anti-tuberculous drugs, between 40-80 years of age, both genders will be included .Patients with history of alcohol use,Discontinuation of drug due to other adverse effects except hepatotoxicity ,Inadequate date of laboratory testing at baseline or 2 to 4 weeks after treatment initiation, Cases with human immunodeficiency virus (HIV) co-infection, viral hepatitis, or suspected mal absorption (e.g., gastrointestinal disease or diarrhea) ,Chronic liver disease, COPD, asthma, myocardial infarction, chronic kidney disease and stroke will be excluded
- Conditions
- Drug Induced Liver Injury, Tuberculosis (TB)
- Being tested
- Silymarin 420 mg, N Acetyl Cysteine, Rifampicin (RMP) Ethambutol (E) Isoniazid (H) Pyrazinamid (Z)
- Keywords
- prevention of Antituberculous drugs induced liver injury
- Medical subject headings
- Chemical and Drug Induced Liver Injury, Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Silymarin 420 mgDrug
silymarin group received silymarin 140mg thrice daily along with antituberculous drugs for 14 days
N Acetyl CysteineDrug
N- acetylcysteine group will receive N-acetylcysteine 900mg once daily with antituberculous drugs for 14 days
Rifampicin (RMP) Ethambutol (E) Isoniazid (H) Pyrazinamid (Z)Drug
Antituberculous drugs only
| Study group | Role | What they receive |
|---|---|---|
| group C | Active comparator | patients taking antituberculous drugs only Receives: Drug: Rifampicin (RMP) Ethambutol (E) Isoniazid (H) Pyrazinamid (Z) |
| group A | Experimental | patients taking antituberculous drugs with silymarin Receives: Drug: Silymarin 420 mg |
| group B | Experimental | patients taking antituberculous drugs with N-acetylcysteine Receives: Drug: N Acetyl Cysteine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Anti-Tuberculous Drug induced Hepatotoxicity
Outcome will be assessed in patients developing Anti-tuberculous Drug-Induced Hepatotoxicity. Patients diagnosed with TB and started on a regimen based on isoniazid, rifampicin, pyrazinamide, and ethambutol will be labeled as having Anti-tuberculous Drug-Induced Hepatotoxicity using liver function tests. It will be labeled if any one of the following criteria is met:
- Rise in alanine aminotransferase (ALT) more than or equal to a fivefold increase from the upper limit of normal (>37 IU/L)
- Rise in alkaline phosphatase (ALP) more than or equal to twofold increase from the upper limit of normal (>147 IU/L).
- An increase in alanine aminotransferase (ALT) to three or more times the upper normal limit (greater than 37 IU/L), accompanied by a simultaneous rise in bilirubin levels to more than twice the upper normal limit (exceeding 1.5 mg/dL), will be considered significant.
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2025
- Study startJul 2025 (estimated)
- Primary completionDec 2025 (estimated)
- Study completionMay 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Drug Induced Liver InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 410 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Liaquat National Hospital & Medical College
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ariba SULTAN, Liaquat National Hospital & Medical College
- Investigators
- Ariba Sultan, Principal investigator, Liaquat National Hospital & Medical College
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07058090
- Sponsor's protocol ID
- 1188-2025-LNH-ERC
- Status last verified
- Jun 2025
- First submitted
- 26 Jun 2025
- Last updated
- 10 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ejigu DA, Abay SM. N-Acetyl Cysteine as an Adjunct in the Treatment of Tuberculosis. Tuberc Res Treat. 2020 Apr 30;2020:5907839. doi: 10.1155/2020/5907839. eCollection 2020.
PubMed 32411461Safe IP, Lacerda MVG, Printes VS, Praia Marins AF, Rebelo Rabelo AL, Costa AA, Tavares MA, Jesus JS, Souza AB, Beraldi-Magalhaes F, Neves CP, Monteiro WM, Sampaio VS, Amaral EP, Gomes RS, Andrade BB, Cordeiro-Santos M. Safety and efficacy of N-acetylcysteine in hospitalized patients with HIV-associated tuberculosis: An open-label, randomized, phase II trial (RIPENACTB Study). PLoS One. 2020 Jun 26;15(6):e0235381. doi: 10.1371/journal.pone.0235381. eCollection 2020.
PubMed 32589648Mahakalkar SM, Nagrale D, Gaur S, Urade C, Murhar B, Turankar A. N-acetylcysteine as an add-on to Directly Observed Therapy Short-I therapy in fresh pulmonary tuberculosis patients: A randomized, placebo-controlled, double-blinded study. Perspect Clin Res. 2017 Jul-Sep;8(3):132-136. doi: 10.4103/2229-3485.210450.
PubMed 28828308Luangchosiri C, Thakkinstian A, Chitphuk S, Stitchantrakul W, Petraksa S, Sobhonslidsuk A. A double-blinded randomized controlled trial of silymarin for the prevention of antituberculosis drug-induced liver injury. BMC Complement Altern Med. 2015 Sep 23;15:334. doi: 10.1186/s12906-015-0861-7.
PubMed 26400476
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of the Outcome of Treatment With Silymarin or N-Aceylcysteine in Patients Taking Anti-Tuberculous Drugs for Tuberculosis at a Tertiary Care Hospital , Karachi
- ClinicalTrials.gov ID
- NCT07058090
- Acronym / sponsor ID
- 1188-2025-LNH-ERC
- Conditions
- Drug Induced Liver Injury, Tuberculosis (TB)
- Keywords
- prevention of Antituberculous drugs induced liver injury
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 410 participants (estimated)
- Lead sponsor
- Liaquat National Hospital & Medical CollegeUniversity, hospital or other
- Study start
- Jul 2025 (estimated)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- May 2026 (estimated)
- First posted
- 10 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
OBJECTIVE : To compare the outcome of treatment with silymarin or N-acetyl cysteine in patients taking anti-tuberculous drugs for tuberculosis at Tertiary Care Hospital, Karachi.
SAMPLE SELECTION : Patients presenting with tuberculosis previously not on anti-tuberculous drugs, between 40-80 years of age, both genders will be included .Patients with history of alcohol use,Discontinuation of drug due to other adverse effects except hepatotoxicity ,Inadequate date of laboratory testing at baseline or 2 to 4 weeks after treatment initiation, Cases with human immunodeficiency virus (HIV) co-infection, viral hepatitis, or suspected mal absorption (e.g., gastrointestinal disease or diarrhea) ,Chronic liver disease, COPD, asthma, myocardial infarction, chronic kidney disease and stroke will be excluded
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| group C | Active comparator | Drug: Rifampicin (RMP) Ethambutol (E) Isoniazid (H) Pyrazinamid (Z)patients taking antituberculous drugs only |
| group A | Experimental | Drug: Silymarin 420 mgpatients taking antituberculous drugs with silymarin |
| group B | Experimental | Drug: N Acetyl Cysteinepatients taking antituberculous drugs with N-acetylcysteine |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients presenting with tuberculosis and previously not on any anti-tuberculous drugs, between 40-80 years of age
- either gender.
Key exclusion criteria (7 listed)
- History of malignancy.
- Patients with history of seropositive, seronegative, connective tissue disorder or vasculitis, congestive cardiac failure.
- Patients with history of alcohol use.
- Discontinuation of drug due to other adverse effects except hepatotoxicity.
- Inadequate date of laboratory testing at baseline or 2 to 4 weeks after treatment initiation.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Silymarin 420 mgsilymarin group received silymarin 140mg thrice daily along with antituberculous drugs for 14 days | Drug | group A |
| N Acetyl CysteineN- acetylcysteine group will receive N-acetylcysteine 900mg once daily with antituberculous drugs for 14 days | Drug | group B |
| Rifampicin (RMP) Ethambutol (E) Isoniazid (H) Pyrazinamid (Z)Antituberculous drugs only | Drug | group C |
Primary outcome
Anti-Tuberculous Drug induced Hepatotoxicity
Time frame: 14 days
Outcome will be assessed in patients developing Anti-tuberculous Drug-Induced Hepatotoxicity. Patients diagnosed with TB and started on a regimen based on isoniazid, rifampicin, pyrazinamide, and ethambutol will be labeled as having Anti-tuberculous Drug-Induced Hepatotoxicity using liver function tests. It will be labeled if any one of the following criteria is met: * Rise in alanine aminotransferase (ALT) more than or equal to a fivefold increase from the upper limit of normal (>37 IU/L) * Rise in alkaline phosphatase (ALP) more than or equal to twofold increase from the upper limit of normal (>147 IU/L). * An increase in alanine aminotransferase (ALT) to three or more times the upper normal limit (greater than 37 IU/L), accompanied by a simultaneous rise in bilirubin levels to more than twice the upper normal limit (exceeding 1.5 mg/dL), will be considered significant.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2025.
- Background: PubMed 32411461Ejigu DA, Abay SM. N-Acetyl Cysteine as an Adjunct in the Treatment of Tuberculosis. Tuberc Res Treat. 2020 Apr 30;2020:5907839. doi: 10.1155/2020/5907839. eCollection 2020.
- Background: PubMed 32589648Safe IP, Lacerda MVG, Printes VS, Praia Marins AF, Rebelo Rabelo AL, Costa AA, Tavares MA, Jesus JS, Souza AB, Beraldi-Magalhaes F, Neves CP, Monteiro WM, Sampaio VS, Amaral EP, Gomes RS, Andrade BB, Cordeiro-Santos M. Safety and efficacy of N-acetylcysteine in hospitalized patients with HIV-associated tuberculosis: An open-label, randomized, phase II trial (RIPENACTB Study). PLoS One. 2020 Jun 26;15(6):e0235381. doi: 10.1371/journal.pone.0235381. eCollection 2020.
- Background: PubMed 28828308Mahakalkar SM, Nagrale D, Gaur S, Urade C, Murhar B, Turankar A. N-acetylcysteine as an add-on to Directly Observed Therapy Short-I therapy in fresh pulmonary tuberculosis patients: A randomized, placebo-controlled, double-blinded study. Perspect Clin Res. 2017 Jul-Sep;8(3):132-136. doi: 10.4103/2229-3485.210450.
- Results publication: PubMed 26400476Luangchosiri C, Thakkinstian A, Chitphuk S, Stitchantrakul W, Petraksa S, Sobhonslidsuk A. A double-blinded randomized controlled trial of silymarin for the prevention of antituberculosis drug-induced liver injury. BMC Complement Altern Med. 2015 Sep 23;15:334. doi: 10.1186/s12906-015-0861-7.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ariba Sultan principal investigator
Liaquat National Hospital & Medical College
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Silymarin 420 mg, N Acetyl Cysteine and Rifampicin (RMP) Ethambutol (E) Isoniazid (H) Pyrazinamid (Z) in people with Drug Induced Liver Injury and Tuberculosis (TB), run by Liaquat National Hospital & Medical College.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 10 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ariba Sultan, MBBS (+92 302 9887711, aaribasultan@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Anti-Tuberculous Drug induced Hepatotoxicity (time frame: 14 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07058090, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2025.