Tuberculosis InfectionINH-DILINCT07472348
Isoniazid-Related Hepatotoxicity in Clinical Practice: Incidence and Predictors
An observational study of Tuberculosis Infection and Tuberculosis Infection, Latent, run by ASST Fatebenefratelli Sacco at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tuberculosis Infection, Tuberculosis Infection, Latent
- What is being tested?
- Standard isoniazid-based TB/LTBI therapy
- How many people
- 220 participants
- Where
- 1 siteItaly
- Study dates
- 30 May 2026to 1 Sep 2026
- Phase
- Observational
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site
ASST Fatebenefratelli Sacco Hospital
Milan, Italy, 20157
Marco Schiuma, Medical Doctor, 0239042685, marco.schiuma@asst-fbf-sacco.it
About this study
Official title: Observational Study on Isoniazid-Induced Hepatotoxicity: Incidence, Risk Factors and Therapeutic Strategies
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:
Read more
- 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.
Read the detailed description
Isoniazid (INH) is an essential drug for the treatment of tuberculosis (TB) and latent tuberculosis infection (LTBI), but it can cause liver damage in a subset of patients. The onset of liver toxicity is often unpredictable and can lead to treatment interruptions, alternative regimens, or incomplete therapy. Despite the widespread use of INH, real-world data describing the incidence, clinical characteristics, and management strategies of INH-induced hepatotoxicity remain limited, especially in European clinical settings.
This single-center, observational study will analyze adults treated for TB or LTBI who received INH as part of their therapeutic regimen. It combines a retrospective cohort (2020-2025) and a prospective cohort (2026-2028), allowing for the evaluation of both historical and current clinical practices. Clinical information already collected during routine care, including demographics, comorbidities, microbiological and imaging findings, anti-TB treatment details, and serial laboratory data, will be used to characterize the development and course of hepatotoxicity.
The study aims to describe the presentation of hepatotoxicity, how it is managed in routine clinical practice, and how clinical decisions, such as modifying antituberculosis therapy or the use of corticosteroids, influence liver recovery and treatment completion. INH-induced hepatotoxicity will be defined using internationally accepted criteria for drug-induced liver injury. Management strategies, including the use of corticosteroids, will be analyzed to understand their impact on biochemical resolution, safety, and treatment outcomes.
Because this is an observational study, no experimental interventions will be administered. All treatments, tests, and clinical decisions will follow standard tuberculosis and LTBI care provided by Luigi Sacco Hospital. Data will be pseudonymized and collected via the electronic case reporting form. The study is expected to provide evidence that can help optimize treatment strategies and support future clinical trials focused on safer management of INH-related liver injury.
- Being tested
- Standard isoniazid-based TB/LTBI therapy
- Keywords
- Isoniazid, INH-induced hepatotoxicity, Drug-induced liver injury, Tuberculosis, Corticosteroid therapy, Observational study, Adverse drug reactions
- Medical subject headings
- Latent Tuberculosis, Chemical and Drug Induced Liver Injury, Tuberculosis, Drug-Related Side Effects and Adverse Reactions
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard isoniazid-based TB/LTBI therapyOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Standard isoniazid-based TB/LTBI therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 (%)
Measured: From treatment initiation to end of TB/LTBI therapy (approximately 6 to 12 months).
Secondary outcomes (4)
Risk factors for isoniazid-induced hepatotoxicity
Identification of demographic, clinical, microbiological, and lifestyle factors associated with isoniazid-induced hepatotoxicity, including comorbidities (e.g., HIV infection and systemic diseases). Associations will be evaluated using multivariable regression models and reported as odds ratios with 95% confidence intervals.
Unit of measure: Odds Ratio (OR)
Measured: During isoniazid treatment and up to 12 months after treatment initiation.
Time to biochemical recovery after hepatotoxicity
Time from the onset of isoniazid-induced hepatotoxicity to normalization of liver enzyme levels (ALT and bilirubin). Unit of measure: Time (days)
Measured: Up to 6 months after hepatotoxicity onset
TB or TBI treatment completion
Proportion of participants completing the planned TB or TBI treatment regimen despite the occurrence of hepatotoxicity. Unit of measure: Percentage of participants (%)
Measured: At the end of TB/TBI therapy (approximately 6-12 months).
Effect of corticosteroid therapy on biochemical recovery
Comparison of time to biochemical recovery between participants with hepatotoxicity treated with corticosteroids and those managed without corticosteroid therapy. Unit of measure: Time to recovery (days)
Measured: Up to 12 months after hepatotoxicity onset
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2026
- Study start30 May 2026 (estimated)
- Primary completion31 Jul 2026 (estimated)
- Study completion1 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tuberculosis InfectionStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 220 participants (estimated)
Sponsor and investigators
- Lead sponsor
- ASST Fatebenefratelli Sacco
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Marco Schiuma, ASST Fatebenefratelli Sacco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07472348
- Sponsor's protocol ID
- INH-DILI-2025
- Acronym
- INH-DILI
- Status last verified
- Mar 2026
- First submitted
- 5 Mar 2026
- Last updated
- 16 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data (IPD) will not be shared because the study uses clinical information collected during routine care, including sensitive health data subject to strict privacy regulations. Many participants in the retrospective cohort cannot be recontacted to obtain consent for data sharing, and the data include information that cannot be fully anonymized without compromising scientific validity. For these reasons, no IPD repository can be created, and access cannot be granted to external researchers.
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Observational Study on Isoniazid-Induced Hepatotoxicity: Incidence, Risk Factors and Therapeutic Strategies
- ClinicalTrials.gov ID
- NCT07472348
- Acronym / sponsor ID
- INH-DILI / INH-DILI-2025
- Keywords
- Isoniazid, INH-induced hepatotoxicity, Drug-induced liver injury, Tuberculosis, Corticosteroid therapy, Observational study, Adverse drug reactions
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 220 participants (estimated)
- Lead sponsor
- ASST Fatebenefratelli SaccoUniversity, hospital or other
- Study start
- 30 May 2026 (estimated)
- Primary completion
- 31 Jul 2026 (estimated)
- Study completion
- 1 Sep 2026 (estimated)
- First posted
- 16 Mar 2026 (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.
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.
Detailed description
Isoniazid (INH) is an essential drug for the treatment of tuberculosis (TB) and latent tuberculosis infection (LTBI), but it can cause liver damage in a subset of patients. The onset of liver toxicity is often unpredictable and can lead to treatment interruptions, alternative regimens, or incomplete therapy. Despite the widespread use of INH, real-world data describing the incidence, clinical characteristics, and management strategies of INH-induced hepatotoxicity remain limited, especially in European clinical settings.
This single-center, observational study will analyze adults treated for TB or LTBI who received INH as part of their therapeutic regimen. It combines a retrospective cohort (2020-2025) and a prospective cohort (2026-2028), allowing for the evaluation of both historical and current clinical practices. Clinical information already collected during routine care, including demographics, comorbidities, microbiological and imaging findings, anti-TB treatment details, and serial laboratory data, will be used to characterize the development and course of hepatotoxicity.
The study aims to describe the presentation of hepatotoxicity, how it is managed in routine clinical practice, and how clinical decisions, such as modifying antituberculosis therapy or the use of corticosteroids, influence liver recovery and treatment completion. INH-induced hepatotoxicity will be defined using internationally accepted criteria for drug-induced liver injury. Management strategies, including the use of corticosteroids, will be analyzed to understand their impact on biochemical resolution, safety, and treatment outcomes.
Because this is an observational study, no experimental interventions will be administered. All treatments, tests, and clinical decisions will follow standard tuberculosis and LTBI care provided by Luigi Sacco Hospital. Data will be pseudonymized and collected via the electronic case reporting form. The study is expected to provide evidence that can help optimize treatment strategies and support future clinical trials focused on safer management of INH-related liver injury.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| INH-treated Cohort | – | Other: Standard isoniazid-based TB/LTBI therapyAdults (≥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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
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 |
|---|---|---|
| Standard isoniazid-based TB/LTBI therapyIsoniazid 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. | Other | INH-treated Cohort |
Primary outcome
Incidence of isoniazid-induced hepatotoxicity in adults treated for TB or LTBI
Time frame: From treatment initiation to end of TB/LTBI therapy (approximately 6 to 12 months).
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 (%)
4 secondary outcomes
Risk factors for isoniazid-induced hepatotoxicity
Time frame: During isoniazid treatment and up to 12 months after treatment initiation.
Time to biochemical recovery after hepatotoxicity
Time frame: Up to 6 months after hepatotoxicity onset
TB or TBI treatment completion
Time frame: At the end of TB/TBI therapy (approximately 6-12 months).
Effect of corticosteroid therapy on biochemical recovery
Time frame: Up to 12 months after hepatotoxicity onset
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 16 Mar 2026.
- Individual participant dataSharing planned: No. Individual participant data (IPD) will not be shared because the study uses clinical information collected during routine care, including sensitive health data subject to strict privacy regulations. Many participants in the retrospective cohort cannot be recontacted to obtain consent for data sharing, and the data include information that cannot be fully anonymized without compromising scientific validity. For these reasons, no IPD repository can be created, and access cannot be granted to external researchers.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Tuberculosis Infection and Tuberculosis Infection, Latent, run by ASST Fatebenefratelli Sacco at 1 site in Italy.
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 4 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 16 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
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.
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 Marco Schiuma, MD (+39 0239042685, schiuma.marco@asst-fbf-sacco.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of isoniazid-induced hepatotoxicity in adults treated for TB or LTBI (time frame: From treatment initiation to end of TB/LTBI therapy (approximately 6 to 12 months).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Mar 2026.