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

Tuberculosis Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05413551
• Other study ID #: 65808
• Secondary ID: 1R21AI172182-01
• Status: Recruiting
• Phase: Phase 1
• Start date: March 23, 2023
• Est. completion date: September 30, 2024

Study information

• Verified date: December 2023
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 72
• Est. completion date: September 30, 2024
• Est. primary completion date: July 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Latent Tuberculosis
• Tuberculosis
• Tuberculosis Infection

Intervention

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

Locations

Country	Name	City	State
Brazil	Federal University of Mato Grosso do Sul	Campo Grande	Mato Grosso Do Sul

Sponsors (4)

Lead Sponsor	Collaborator
Stanford University	Federal University of Mato Grosso, Fiocruz Mato Grosso do Sul, National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

Brazil, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Isoniazid plasma area-under-the-curve		1, 2, 8, and 24 hours post-dose
Secondary	Maximum isoniazid concentration (Cmax)		1, 2, 8, and 24 hours post-dose
Secondary	Isoniazid concentration at 24 hours		24 hours post-dose