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

Stanford University

Status and phase: Completed; Phase 1

Conditions: Tuberculosis Infection; Isoniazid Adverse Reaction

Treatments: Drug: High-dose isoniazid; Drug: Standard dose of isoniazid; Drug: Low-dose isoniazid

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05413551

65808

1R21AI172182-01 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Enrollment: 73 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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73 participants in 3 patient groups

Rapid acetylator

Experimental group

Description:

Participants will receive 1 standard dose (Day 0), followed by 1 higher dose (Day 7), follow by 2 standard doses (Days 14 and 21).

Treatment:

Drug: Standard dose of isoniazid

Drug: High-dose isoniazid

Intermediate acetylator

Active Comparator group

Description:

Participants will receive 4 standard doses (Days 0, 7, 14 and 21).

Treatment:

Drug: Standard dose of isoniazid

Slow acetylator

Experimental group

Description:

Participants will receive 2 standard doses (Days 0 and 7), followed by 1 lower dose (Day 21), follow by 1 standard dose (Day 21).

Treatment:

Drug: Low-dose isoniazid

Drug: Standard dose of isoniazid