Isoniazid-Related Hepatotoxicity in Clinical Practice: Incidence and Predictors

NCT07472348 | Not Yet Recruiting

• 1 other identifier: INH-DILI-2025
• Study Type: observational
• Target: 220
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this observational study is to determine how frequently isoniazid (INH) causes liver injury (hepatotoxicity) in adults treated for tuberculosis (TB) or latent tuberculosis infection (LTBI) and to understand which factors increase this risk. The study also aims to describe how hepatotoxicity is managed in real-world clinical practice and whether treatments such as corticosteroids can improve liver function tests. The main questions this study aims to answer are:

• How frequently does INH-induced hepatotoxicity occur in adults treated for TB or LTBI?
• What demographic, clinical, microbiological, or lifestyle factors increase the risk of developing hepatotoxicity?
• How do different management strategies, including treatment modification or the use of corticosteroids, affect liver recovery and completion of TB/LTBI therapy? This study does not involve experimental treatments. Researchers will analyze information already collected during routine clinical care, both retrospectively (from 2020 to 2025) and prospectively (2026-2028). There is no comparison group, but participants may have different clinical profiles or treatments, which will be compared to understand risk factors and outcomes. Participants will:
• Receive standard treatment for tuberculosis or LTBI, including isoniazid, as prescribed by their treating physicians.
• Undergo routine assessments, such as blood tests, microbiology, imaging, and clinic visits, as part of their regular care.
• Their clinical data will be recorded in the study database to analyze liver function trends, treatment changes, and outcomes. The study will contribute to improving understanding of INH-induced hepatotoxicity and supporting safer and more effective treatment strategies for tuberculosis and LTBI.

Conditions

Tuberculosis Infection; Tuberculosis Infection, Latent

Keywords

Isoniazid; INH-induced hepatotoxicity; Drug-induced liver injury; Tuberculosis; Corticosteroid therapy; Observational study; Adverse drug reactions

Outcome Measures

Primary Outcomes (1)

• Incidence of isoniazid-induced hepatotoxicity in adults treated for TB or LTBI

  Proportion (%) of participants developing hepatotoxicity during treatment with isoniazid, defined according to international DILI criteria (ALT \>5× ULN and/or bilirubin \>3x ULN or ALT \>3× ULN and/or bilirubin \>2x ULN with symptoms). Unit of measure: Percentage of participants (%)

  From treatment initiation to end of TB/LTBI therapy (approximately 6 to 12 months).

Secondary Outcomes (4)

• Risk factors for isoniazid-induced hepatotoxicity

  During isoniazid treatment and up to 12 months after treatment initiation.

• Time to biochemical recovery after hepatotoxicity

  Up to 6 months after hepatotoxicity onset

• TB or TBI treatment completion

  At the end of TB/TBI therapy (approximately 6-12 months).

• Effect of corticosteroid therapy on biochemical recovery

  Up to 12 months after hepatotoxicity onset

Study Arms (1)

INH-treated Cohort

Adults (≥18 years) diagnosed with tuberculosis (TB) or latent TB infection (LTBI) who received isoniazid as part of their standard treatment regimen. This cohort includes both retrospective participants (treated between 2020-2025) and prospective participants (2026-2028). No experimental interventions are administered; all treatments follow routine clinical care.

Other: Standard isoniazid-based TB/LTBI therapy

Interventions

Standard isoniazid-based TB/LTBI therapy OTHER

Isoniazid administered as part of routine tuberculosis or latent tuberculosis infection treatment, according to standard clinical guidelines. The study observes real-world outcomes and does not assign or modify therapeutic regimens.

INH-treated Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Study participants will be adults being treated for TB or LTBI at the Department of Infectious Diseases at Luigi Sacco Hospital in Milan, a regional referral center for TB management. The population includes individuals treated both inpatient and outpatient settings, whose clinical, laboratory, imaging, microbiological, and treatment data were routinely collected as part of standard care. The study comprises two sources: a retrospective cohort of adults treated with isoniazid between 2020 and 2025 and a prospective cohort enrolled between 2026 and 2028. Together, these groups represent the real-world patient population managed at this center for the treatment of TB and LTBI.

You may qualify if:

• Adults aged ≥18 years.
• Patients diagnosed with TB or LTBI who received INH as part of their treatment regimen (either first-line or second-line therapy), regardless of combination with other anti-TB drugs.
• Normal baseline liver function tests (ALT, AST and bilirubin within reference range) and absence of clinical symptoms of liver dysfunction prior to initiation of anti-TB therapy.
• Signed informed consent.

You may not qualify if:

• Patients who did not receive isoniazid during their treatment course.
• Pre-existing liver dysfunction, including biliary origin, before anti-TB therapy.
• Pregnancy or lactation.
• Concomitant use of non-TB hepatotoxic drugs.
• Abnormal hepatic function on baseline laboratory testing.
• Known INH resistance at treatment initiation.
• Refusal to provide informed consent.

Sponsors & Collaborators

• ASST Fatebenefratelli Sacco: lead

Study Sites (1)

ASST Fatebenefratelli Sacco Hospital

Milan, Italy, 20157, Italy

Location

MeSH Terms

Conditions

Latent Tuberculosis; Chemical and Drug Induced Liver Injury; Tuberculosis; Drug-Related Side Effects and Adverse Reactions

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Latent Infection; Liver Diseases; Digestive System Diseases; Chemically-Induced Disorders; Poisoning

Central Study Contacts

Marco Schiuma, MD

CONTACT

+39 0239042685; schiuma.marco@asst-fbf-sacco.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor

Study Record Dates

• First Submitted: March 5, 2026
• First Posted: March 16, 2026
• Study Start: May 30, 2026
• Primary Completion: July 31, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: March 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)