Tuberculosis InfectionPhase 1NCT05413551

Point-of-care Pharmacogenomic Testing to Optimize Isoniazid Dosing for Tuberculosis Prevention

A Phase 1 study testing Low-dose isoniazid, Standard dose of isoniazid and High-dose isoniazid in people with Tuberculosis Infection and Isoniazid Adverse Reaction, run by Stanford University at 1 site in Brazil.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Tuberculosis Infection, Isoniazid Adverse Reaction
What is being tested?: Low-dose isoniazid, Standard dose of isoniazid and High-dose isoniazid
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 78 participants
Where: 1 siteBrazil
Study dates: 23 Mar 2023to 25 Jun 2025
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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

Who may be able to join

Eligible for latent tuberculosis treatment by Brazil's national guidelines*
provides written informed consent to participate in the study

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

Brazil1 site

Federal University of Mato Grosso do Sul
Campo Grande, Mato Grosso do Sul

Other trials in Brazil

About this study

Conditions: Tuberculosis Infection, Isoniazid Adverse Reaction
Being tested: Low-dose isoniazid, Standard dose of isoniazid, High-dose isoniazid
Medical subject headings: Latent Tuberculosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Low-dose isoniazidDrug
Pharmacogenomic-modified dose of isoniazid - 5 mg/kg oral tablet (maximum 300 mg)
Standard dose of isoniazidDrug
15 mg/kg oral tablet (up to 900 mg)
High-dose isoniazidDrug
Pharmacogenomic-modified dose of isoniazid - 25 mg/kg oral tablet (maximum 1500 mg)

Study groups in NCT05413551
Study group	Role	What they receive
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). Receives: Drug: Standard dose of isoniazid; Drug: High-dose isoniazid
Intermediate acetylator	Active comparator	Participants will receive 4 standard doses (Days 0, 7, 14 and 21). Receives: Drug: Standard dose of isoniazid
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). Receives: Drug: Low-dose isoniazid; Drug: Standard dose of isoniazid

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: Days 7 and 14 (1, 2, 8, and 24 hours post-dose)

Secondary outcomes (2)

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
Measured: Days 7 and 14 (1, 2, 8, and 24 hours post-dose)
Isoniazid Concentration at 24 Hours
Isoniazid plasma concentration measured at 24 hours post-dose.
Measured: Days 7 and 14 (24 hours post-dose)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

23 Mar 202325 Jun 2025

First posted10 Jun 2022
Study start23 Mar 2023
Primary completion23 Apr 2025
Study completion25 Jun 2025

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Tuberculosis InfectionStudies of the same condition, open and under way.
More trials run by Stanford UniversityThe sponsor's other registered studies.
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: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 78 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05413551
Sponsor's protocol ID: 65808
Other IDs: 1R21AI172182-01
Status last verified: May 2026
First submitted: 7 Jun 2022
Last updated: 15 Jun 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: We will make the study protocol, statistical analysis plan, informed consent form and report available. We will make a de-identified dataset available.

Publications

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.
PubMed 34375564

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
Paradoxical Tuberculosis Reactions in Patients Without HIV Infection
Tuberculosis
Not yet recruitingPhase 2
Re-evaluating the Duration in Children of TB Treatment
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RecruitingPhase 1/2
A Study of Daily Rifapentine Combined With Isoniazid (1HP) for Tuberculosis Prevention in Children Less Than 13 Years of Age With and Without HIV
Tuberculosis
Active, not recruitingPhase 3
Protecting Households On Exposure to Newly Diagnosed Index Multidrug-Resistant Tuberculosis Patients
Tuberculosis, MDR
RecruitingPhase 2
Evaluating the Safety and Immunogenicity of MTBVAC
HIV I Infection, Tuberculosis

All Tuberculosis Infection trials

Study at a glance

From the registry record, last updated by the sponsor on 15 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Point-of-care Pharmacogenomic Testing to Optimize Isoniazid Dosing for Tuberculosis Prevention
ClinicalTrials.gov ID: NCT05413551
Acronym / sponsor ID: 65808
Conditions: Tuberculosis Infection, Isoniazid Adverse Reaction
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 78 participants (actual)
Lead sponsor: Stanford UniversityUniversity, hospital or other
Collaborators: National Institute of Allergy and Infectious Diseases (NIAID), Federal University of Mato Grosso, Fiocruz Mato Grosso do Sul
Study start: 23 Mar 2023 (actual)
Primary completion: 23 Apr 2025 (actual)
Study completion: 25 Jun 2025 (actual)
First posted: 10 Jun 2022 (actual)
Results: Posted 15 Jun 2026

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Rapid acetylator	Experimental	Drug: Standard dose of isoniazid, Drug: High-dose isoniazidParticipants 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	Drug: Standard dose of isoniazidParticipants will receive 4 standard doses (Days 0, 7, 14 and 21).
Slow acetylator	Experimental	Drug: Low-dose isoniazid, Drug: Standard dose of isoniazidParticipants will receive 2 standard doses (Days 0 and 7), followed by 1 lower dose (Day 21), follow by 1 standard dose (Day 21).

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

Eligible for latent tuberculosis treatment by Brazil's national guidelines*
provides written informed consent to participate in the study

Key exclusion criteria (8 listed)

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

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
Low-dose isoniazidPharmacogenomic-modified dose of isoniazid - 5 mg/kg oral tablet (maximum 300 mg)	Drug	Slow acetylator
Standard dose of isoniazid15 mg/kg oral tablet (up to 900 mg)	Drug	Intermediate acetylator, Rapid acetylator, Slow acetylator
High-dose isoniazidPharmacogenomic-modified dose of isoniazid - 25 mg/kg oral tablet (maximum 1500 mg)	Drug	Rapid acetylator

Primary outcome

Isoniazid Plasma Area-under-the-curve
Time frame: 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
Time frame: 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.

2 secondary outcomes

Maximum Isoniazid Concentration (Cmax)
Time frame: Days 7 and 14 (1, 2, 8, and 24 hours post-dose)
Isoniazid Concentration at 24 Hours
Time frame: Days 7 and 14 (24 hours post-dose)

Results and safety

Results posted to the registry on 15 Jun 2026, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Rapid Acetylator	10	9
Intermediate Acetylator	34	27
Slow Acetylator	34	26

Primary outcome: Isoniazid Plasma Area-under-the-curve

Time frame: Days 7 and 14 (1, 2, 8, and 24 hours post-dose). Median (Inter-Quartile Range). Unit: mg·h/L

Measure	Rapid Acetylator n = 10	Intermediate Acetylator n = 34	Slow Acetylator n = 34
900 mg Flat Dosing (day 14 post-dose)	24.4 (19.7 to 26.1)	31.0 (26.9 to 34.9)	57.6 (50.4 to 62.3)
Genotype-Based Dosing (day 7 post-dose)	40.7 (32.9 to 43.6)	30.6 (27.1 to 34.9)	18.3 (16.3 to 20.3)

Primary outcome: Isoniazid Clearance

Time frame: Days 7 and 14 (1, 2, 8, and 24 hours post-dose). Mean (Standard Error). Unit: L/h

Measure	Rapid Acetylator n = 10	Intermediate Acetylator n = 34	Slow Acetylator n = 34
Value	38.5 (9.78)	30.3 (2.02)	17.6 (2.09)

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: 12 weeks. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Rapid Acetylator	0 of 10 (0%)	7 of 10 (70%)	0 of 10
Intermediate Acetylator	2 of 34 (5.9%)	22 of 34 (64.7%)	0 of 34
Slow Acetylator	0 of 34 (0%)	24 of 34 (70.6%)	0 of 34

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 34375564Verma 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.
Individual participant dataSharing planned: Yes. We will make the study protocol, statistical analysis plan, informed consent form and report available. We will make a de-identified dataset available.

Related trials for Tuberculosis Infection

RecruitingObservational study
Paradoxical Tuberculosis Reactions in Patients Without HIV Infection
Tuberculosis
Not yet recruitingPhase 2
Re-evaluating the Duration in Children of TB Treatment
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RecruitingPhase 1/2
A Study of Daily Rifapentine Combined With Isoniazid (1HP) for Tuberculosis Prevention in Children Less Than 13 Years of Age With and Without HIV
Tuberculosis
Active, not recruitingPhase 3
Protecting Households On Exposure to Newly Diagnosed Index Multidrug-Resistant Tuberculosis Patients
Tuberculosis, MDR
RecruitingPhase 2
Evaluating the Safety and Immunogenicity of MTBVAC
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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. This study is not recruiting at the moment.

Jason R Andrews, MD principal investigator

Stanford University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 2 inclusion and 8 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: finished, as of the sponsor's last update on 15 Jun 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 Brazil. 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.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Jun 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Isoniazid Plasma Area-under-the-curve (time frame: Days 7 and 14 (1, 2, 8, and 24 hours post-dose)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05413551, which also lists 1 linked publication.

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 15 Jun 2026.