Isoniazid Adverse Reaction, Tuberculosis Infection
Conditions
Brief summary
This trial is designed to determine whether modifying the dose of isoniazid for individuals according to their n-acetyltransferase 2 (NAT2) genotype could increase the probability of achieving equivalence of area-under-the-curve.
Interventions
DRUGLow-dose isoniazid
Pharmacogenomic-modified dose of isoniazid - 5 mg/kg oral tablet (maximum 300 mg)
DRUGStandard dose of isoniazid
15 mg/kg oral tablet (up to 900 mg)
DRUGHigh-dose isoniazid
Pharmacogenomic-modified dose of isoniazid - 25 mg/kg oral tablet (maximum 1500 mg)
Sponsors
Stanford University
National Institute of Allergy and Infectious Diseases (NIAID)
Federal University of Mato Grosso
Fiocruz Mato Grosso do Sul
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Eligible for latent tuberculosis treatment by Brazil's national guidelines\* * provides written informed consent to participate in the study
Exclusion criteria
* Evidence of active tuberculosis or currently under evaluation for active tuberculosis * Receiving drugs that interact with Rifapentine (e.g. methadone, warfarin) * Known intolerance or hypersensitivity to isoniazid or rifapentine * Prior treatment for active or latent tuberculosis \> 14 days * Close contact to isoniazid- or rifampicin-resistant tuberculosis (TB) case * Neutropenia (absolute neutrophil count \<1000 cells/mm3) * Clinical diagnosis of active liver disease or alcohol dependence * alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>3 times the upper limit of normal
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Isoniazid Plasma Area-under-the-curve | Days 7 and 14 (1, 2, 8, and 24 hours post-dose) | Area under the plasma concentration-time curve over 24 hours (AUC₀-₂₄) for isoniazid, estimated using a population pharmacokinetic model based on plasma concentrations collected at 1, 2, 8, and 24 hours post-dose on Days 7 and 14. |
| Isoniazid Clearance | Days 7 and 14 (1, 2, 8, and 24 hours post-dose) | Apparent clearance (CL) of isoniazid estimated from a population pharmacokinetic model using plasma concentration data collected at 1, 2, 8, and 24 hours post-dose on Days 7 and 14. Clearance values represent model-derived population parameter estimates. Data across the day 7 and day 14 time points are combined to provide an estimated value as a model parameter, representing the typical value per group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Isoniazid Concentration (Cmax) | Days 7 and 14 (1, 2, 8, and 24 hours post-dose) | Maximum observed plasma concentration (Cmax) of isoniazid following dosing, derived from serial plasma samples collected at 1, 2, 8, and 24 hours post-dose |
| Isoniazid Concentration at 24 Hours | Days 7 and 14 (24 hours post-dose) | Isoniazid plasma concentration measured at 24 hours post-dose. |
Countries
Brazil
Contacts
PRINCIPAL_INVESTIGATORJason R Andrews, MD
Stanford University
Participant flow
Recruitment details
Participants were recruited in Brazil between March 2023 and June 2025 from clinical, community, and correctional facilities in Campo Grande. Eligible participants included individuals indicated for tuberculosis preventive therapy, including healthcare workers, household contacts, incarcerated individuals, and people living with HIV.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 41.6 Years |
| Alcohol use | 10 Participants |
| Drug-use | 1 Participants |
| Incarceration status | 7 Participants |
| Race/Ethnicity, Customized Race Black | 13 Participants |
| Race/Ethnicity, Customized Race Mixed | 29 Participants |
| Race/Ethnicity, Customized Race White | 31 Participants |
| Race/Ethnicity, Customized Race Yellow | 0 Participants |
| Region of Enrollment Brazil | 78 Participants |
| Sex/Gender, Customized Sex Female | 11 Participants |
| Sex/Gender, Customized Sex Male | 8 Participants |
| Smoking | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 34 | 0 / 34 |
| other Total, other adverse events | 7 / 10 | 22 / 34 | 24 / 34 |
| serious Total, serious adverse events | 0 / 10 | 2 / 34 | 0 / 34 |
Outcome results
None listed