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
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