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

Phase 1

Recruiting

• Conditions: Tuberculosis Infection; Isoniazid Adverse Reaction
• Interventions: Drug: Standard dose of isoniazid; Drug: Low-dose isoniazid; Drug: High-dose isoniazid

• Registration Number: NCT05413551
• Lead Sponsor: Stanford University

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2022-06-07
• Study First Submitted QC: 2022-06-07
• Study First Posted: 2022-06-10
• Study Start: 2023-03-23
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-12
• Last Update Posted: 2024-07-16
• Primary Completion: 2024-10-31
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 72

Inclusion Criteria

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Rapid acetylator	Standard dose of isoniazid	Participants will receive 1 standard dose (Day 0), followed by 1 higher dose (Day 7), follow by 2 standard doses (Days 14 and 21).
Rapid acetylator	High-dose isoniazid	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	Standard dose of isoniazid	Participants will receive 4 standard doses (Days 0, 7, 14 and 21).
Slow acetylator	Low-dose isoniazid	Participants will receive 2 standard doses (Days 0 and 7), followed by 1 lower dose (Day 21), follow by 1 standard dose (Day 21).
Slow acetylator	Standard dose of isoniazid	Participants will receive 2 standard doses (Days 0 and 7), followed by 1 lower dose (Day 21), follow by 1 standard dose (Day 21).

Primary Outcome Measures

Name	Time	Method
Isoniazid plasma area-under-the-curve	1, 2, 8, and 24 hours post-dose

Secondary Outcome Measures

Name	Time	Method
Maximum isoniazid concentration (Cmax)	1, 2, 8, and 24 hours post-dose
Isoniazid concentration at 24 hours	24 hours post-dose

Trial Locations

Locations (1)

Federal University of Mato Grosso do Sul; 🇧🇷 Campo Grande, Mato Grosso Do Sul, Brazil