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

Sponsor

Stanford University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05413551

Collaborator

National Institutes of Health (NIH) (NIH), Federal University of Mato Grosso (Other), Fiocruz Mato Grosso do Sul (Other)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Tuberculosis Infection Isoniazid Adverse Reaction	Drug: Low-dose isoniazid Drug: Standard dose of isoniazid Drug: High-dose isoniazid	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

72 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Sep 1, 2022

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Apr 1, 2024

Arms and Interventions

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: Low-dose isoniazid Pharmacogenomic-modified dose of isoniazid - 5 mg/kg oral tablet (maximum 300 mg) Drug: Standard dose of isoniazid 15 mg/kg oral tablet (up to 900 mg)

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: Low-dose isoniazid

Pharmacogenomic-modified dose of isoniazid - 5 mg/kg oral tablet (maximum 300 mg)

Drug: Standard dose of isoniazid

15 mg/kg oral tablet (up to 900 mg)

Outcome Measures

Primary Outcome Measures

Isoniazid plasma area-under-the-curve [1, 2, 8, and 24 hours post-dose]

Secondary Outcome Measures

Maximum isoniazid concentration (Cmax) [1, 2, 8, and 24 hours post-dose]
Isoniazid concentration at 24 hours [24 hours post-dose]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Stanford University
National Institutes of Health (NIH)
Federal University of Mato Grosso
Fiocruz Mato Grosso do Sul

Investigators

Principal Investigator: Jason R Andrews, MD, Stanford University

Study Documents (Full-Text)

None provided.

More Information

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.

Responsible Party:

Jason Andrews, Associate Professor of Medicine, Stanford University

ClinicalTrials.gov Identifier:

NCT05413551

Other Study ID Numbers:

65808

First Posted:

Jun 10, 2022

Last Update Posted:

Jun 10, 2022

Last Verified:

Jun 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Tuberculosis

Latent Tuberculosis

Isoniazid

Study Results

No Results Posted as of Jun 10, 2022