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| ID | Type | Description | Link |
|---|---|---|---|
| 1R21AI172182-01 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Allergy and Infectious Diseases (NIAID) | NIH |
| Federal University of Mato Grosso | OTHER |
| Fiocruz Mato Grosso do Sul | UNKNOWN |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Rapid acetylator | Experimental | Participants will receive 1 standard dose (Day 0), followed by 1 higher dose (Day 7), follow by 2 standard doses (Days 14 and 21). |
|
| Intermediate acetylator | Active Comparator | Participants will receive 4 standard doses (Days 0, 7, 14 and 21). |
|
| Slow acetylator | Experimental | Participants will receive 2 standard doses (Days 0 and 7), followed by 1 lower dose (Day 21), follow by 1 standard dose (Day 21). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Low-dose isoniazid | Drug | Pharmacogenomic-modified dose of isoniazid - 5 mg/kg oral tablet (maximum 300 mg) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Isoniazid Plasma Area-under-the-curve | Area under the plasma concentration-time curve over 24 hours (AUCâ‚€-â‚‚â‚„) 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. | Days 7 and 14 (1, 2, 8, and 24 hours post-dose) |
| Isoniazid Clearance | 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. | Days 7 and 14 (1, 2, 8, and 24 hours post-dose) |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Isoniazid Concentration (Cmax) | Maximum observed plasma concentration (Cmax) of isoniazid following dosing, derived from serial plasma samples collected at 1, 2, 8, and 24 hours post-dose | Days 7 and 14 (1, 2, 8, and 24 hours post-dose) |
| Isoniazid Concentration at 24 Hours |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jason R Andrews, MD | Stanford University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Federal University of Mato Grosso do Sul | Campo Grande | Mato Grosso do Sul | Brazil |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34375564 | Background | Verma R, Patil S, Zhang N, Moreira FMF, Vitorio MT, Santos ADS, Wallace E, Gnanashanmugam D, Persing DH, Savic RM, Croda J, Andrews JR. A Rapid Pharmacogenomic Assay to Detect NAT2 Polymorphisms and Guide Isoniazid Dosing for Tuberculosis Treatment. Am J Respir Crit Care Med. 2021 Dec 1;204(11):1317-1326. doi: 10.1164/rccm.202103-0564OC. |
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We will make the study protocol, statistical analysis plan, informed consent form and report available. We will make a de-identified dataset available.
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Rapid Acetylator | Participants will receive 1 standard dose (Day 0), followed by 1 higher dose (Day 7), follow by 2 standard doses (Days 14 and 21). |
| FG001 | Intermediate Acetylator | Participants will receive 4 standard doses (Days 0, 7, 14 and 21). |
| FG002 | Slow Acetylator | Participants will receive 1 standard dose (Day 0), followed by 1 lower dose (Day 7), followed by 2 standard doses (Days 14 and 21). |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Baseline characteristics are presented for all participants included in the study, and the analysis population is the same as the number assigned to the study groups.
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| ID | Title | Description |
|---|---|---|
| BG000 | Rapid Acetylator | Participants will receive 1 standard dose (Day 0), followed by 1 higher dose (Day 7), follow by 2 standard doses (Days 14 and 21). |
| BG001 | Intermediate Acetylator |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Secondary | Maximum Isoniazid Concentration (Cmax) | Maximum observed plasma concentration (Cmax) of isoniazid following dosing, derived from serial plasma samples collected at 1, 2, 8, and 24 hours post-dose | Posted | Median | Inter-Quartile Range | µg/mL | Days 7 and 14 (1, 2, 8, and 24 hours post-dose) |
|
12 weeks
All adverse events were reported regardless of frequency
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Rapid Acetylator | Participants will receive 1 standard dose (Day 0), followed by 1 higher dose (Day 7), follow by 2 standard doses (Days 14 and 21). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Palpitation | Cardiac disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Palpitations | Cardiac disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jason Andrews, Professor | Stanford University | +16504972679 | jandr@stanford.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 4, 2024 | May 18, 2026 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Aug 4, 2023 | Apr 17, 2026 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D055985 | Latent Tuberculosis |
| ID | Term |
|---|---|
| D014376 | Tuberculosis |
| D009164 | Mycobacterium Infections |
| D000193 | Actinomycetales Infections |
| D016908 | Gram-Positive Bacterial Infections |
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| ID | Term |
|---|---|
| D007538 | Isoniazid |
| ID | Term |
|---|---|
| D006834 | Hydrazines |
| D009930 | Organic Chemicals |
| D007539 | Isonicotinic Acids |
| D000147 | Acids, Heterocyclic |
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| Standard dose of isoniazid | Drug | 15 mg/kg oral tablet (up to 900 mg) |
|
| High-dose isoniazid | Drug | Pharmacogenomic-modified dose of isoniazid - 25 mg/kg oral tablet (maximum 1500 mg) |
|
Isoniazid plasma concentration measured at 24 hours post-dose. |
| Days 7 and 14 (24 hours post-dose) |
Participants will receive 4 standard doses (Days 0, 7, 14 and 21).
| BG002 | Slow Acetylator | Participants will receive 1 standard dose (Day 0), followed by 1 lower dose (Day 7), followed by 2 standard doses (Days 14 and 21). |
| BG003 | Total | Total of all reporting groups |
| Years |
|
| Sex/Gender, Customized | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Race/skin color at the time of study enrollment, categorized based on participant self-report using standard Brazilian census categories (White, Black, Mixed, and Yellow). | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Incarceration status | Number of participants who were incarcerated at the time of study enrollment | Count of Participants | Participants |
|
| Smoking | Number of participants who reported use of tobacco | Count of Participants | Participants |
|
| Alcohol use | Number of participants who reported use of alcohol | Count of Participants | Participants |
|
| Drug-use | Number of participants who reported use of non-prescribed or illicit substances | Count of Participants | Participants |
|
| Slow Acetylator |
Participants will receive 1 standard dose (Day 0), followed by 1 lower dose (Day 7), followed by 2 standard doses (Days 14 and 21). |
|
|
| Secondary | Isoniazid Concentration at 24 Hours | Isoniazid plasma concentration measured at 24 hours post-dose. | Posted | Median | Inter-Quartile Range | µg/mL | Days 7 and 14 (24 hours post-dose) |
|
|
|
| Primary | Isoniazid Plasma Area-under-the-curve | 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. | Posted | Median | Inter-Quartile Range | mg·h/L | Days 7 and 14 (1, 2, 8, and 24 hours post-dose) |
|
|
|
| Primary | Isoniazid Clearance | 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. | Posted | Mean | Standard Error | L/h | Days 7 and 14 (1, 2, 8, and 24 hours post-dose) |
|
|
|
| 0 |
| 10 |
| 0 |
| 10 |
| 7 |
| 10 |
| EG001 | Intermediate Acetylator | Participants will receive 4 standard doses (Days 0, 7, 14 and 21). | 0 | 34 | 2 | 34 | 22 | 34 |
| EG002 | Slow Acetylator | Participants will receive 1 standard dose (Day 0), followed by 1 lower dose (Day 7), followed by 2 standard doses (Days 14 and 21). | 0 | 34 | 0 | 34 | 24 | 34 |
| Dizziness with presyncope | Nervous system disorders | Systematic Assessment |
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| Oral ulcer | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Headache | Nervous system disorders | Systematic Assessment |
|
| fatigue and somnolence | Nervous system disorders | Systematic Assessment |
|
| Renal colic | Renal and urinary disorders | Systematic Assessment |
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| Epigastric pain | Gastrointestinal disorders | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Anxiety | Psychiatric disorders | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Fever | General disorders | Systematic Assessment |
|
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| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D000085343 | Latent Infection |
| D006571 |
| Heterocyclic Compounds |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| Genotype-Based Dosing (day 7 post-dose) |
|
| Genotype-Based Dosing (day 7 post-dose) |
|