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

NCT07058090 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: 1188-2025-LNH-ERC
• Study Type: interventional
• Target: 410
• Locations: 0 countries
• Sites: N/A

Brief 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. 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)

Keywords

prevention of Antituberculous drugs induced liver injury

Outcome Measures

Primary Outcomes (1)

• 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.

  14 days

Study Arms (3)

group C

ACTIVE COMPARATOR

patients taking antituberculous drugs only

Drug: Rifampicin (RMP) Ethambutol (E) Isoniazid (H) Pyrazinamid (Z)

group A

EXPERIMENTAL

patients taking antituberculous drugs with silymarin

Drug: Silymarin 420 mg

group B

EXPERIMENTAL

patients taking antituberculous drugs with N-acetylcysteine

Drug: N Acetyl Cysteine

Interventions

Silymarin 420 mg DRUG

silymarin group received silymarin 140mg thrice daily along with antituberculous drugs for 14 days

group A

N Acetyl Cysteine DRUG

N- acetylcysteine group will receive N-acetylcysteine 900mg once daily with antituberculous drugs for 14 days

group B

Rifampicin (RMP) Ethambutol (E) Isoniazid (H) Pyrazinamid (Z) DRUG

Antituberculous drugs only

group C

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients presenting with tuberculosis and previously not on any anti-tuberculous drugs, between 40-80 years of age
• either gender.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Liaquat National Hospital & Medical College: lead

Related Publications (4)

• Luangchosiri 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.

  PMID: 26400476 BACKGROUND

• 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.

  PMID: 32411461 BACKGROUND

• Safe 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.

  PMID: 32589648 BACKGROUND

• Mahakalkar 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.

  PMID: 28828308 BACKGROUND

MeSH Terms

Conditions

Chemical and Drug Induced Liver Injury; Tuberculosis

Interventions

Silymarin; Acetylcysteine; Rifampin; Ethambutol; Isoniazid; Protons; Pyrazinamide

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Poisoning; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Flavonolignans; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Ethylenediamines; Diamines; Polyamines; Amines; Hydrazines; Isonicotinic Acids; Acids, Heterocyclic; Pyridines; Cations, Monovalent; Cations; Ions; Electrolytes; Inorganic Chemicals; Hydrogen; Elements; Gases; Nucleons; Elementary Particles; Physical Phenomena; Pyrazines

Study Officials

• Ariba Sultan

  Liaquat National Hospital & Medical College

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ariba Sultan, MBBS

CONTACT

+92 302 9887711; aaribasultan@gmail.com

shameem behram khan, fcps

CONTACT

+92 332 2397924; drshameem26@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: June 26, 2025
• First Posted: July 10, 2025
• Study Start: July 1, 2025
• Primary Completion: December 1, 2025
• Study Completion: May 1, 2026
• Last Updated: July 10, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share