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

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.

Study Overview

• Status: Completed
• Conditions: Tuberculosis Infection; Isoniazid Adverse Reaction
• Intervention / Treatment: Drug: Standard dose of isoniazid; Drug: High-dose isoniazid; Drug: Low-dose isoniazid

• Study Type: Interventional
• Enrollment (Actual): 73
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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).	Drug: Standard dose of isoniazid; 15 mg/kg oral tablet (up to 900 mg); Drug: High-dose isoniazid; Pharmacogenomic-modified dose of isoniazid - 25 mg/kg oral tablet (maximum 1500 mg)
Active Comparator: Intermediate acetylator; Participants will receive 4 standard doses (Days 0, 7, 14 and 21).	Drug: Standard dose of isoniazid; 15 mg/kg oral tablet (up to 900 mg)
Experimental: Slow acetylator; Participants will receive 2 standard doses (Days 0 and 7), followed by 1 lower dose (Day 21), follow by 1 standard dose (Day 21).	Drug: Standard dose of isoniazid; 15 mg/kg oral tablet (up to 900 mg); Drug: Low-dose isoniazid; Pharmacogenomic-modified dose of isoniazid - 5 mg/kg oral tablet (maximum 300 mg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Isoniazid plasma area-under-the-curve	1, 2, 8, and 24 hours post-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum isoniazid concentration (Cmax)	1, 2, 8, and 24 hours post-dose
Isoniazid concentration at 24 hours	24 hours post-dose

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); Federal University of Mato Grosso; Fiocruz Mato Grosso do Sul
• Investigators: Principal Investigator: Jason R Andrews, MD, Stanford University

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2023
• Primary Completion (Actual): April 23, 2025
• Study Completion (Actual): June 25, 2025

Study Registration Dates

• First Submitted: June 7, 2022
• First Submitted That Met QC Criteria: June 7, 2022
• First Posted (Actual): June 10, 2022

Study Record Updates

• Last Update Posted (Estimated): December 17, 2025
• Last Update Submitted That Met QC Criteria: December 14, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Latent Infection; Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Latent Tuberculosis; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydrazines; Isonicotinic Acids; Acids, Heterocyclic; Isoniazid
• Other Study ID Numbers: 65808; 1R21AI172182-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We will make the study protocol, statistical analysis plan, informed consent form and report available. We will make a de-identified dataset available.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No