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

Primary Purpose

Tuberculosis Infection, Isoniazid Adverse Reaction

Status
Recruiting
Phase
Phase 1
Locations
Brazil
Study Type
Interventional
Intervention
Low-dose isoniazid
Standard dose of isoniazid
High-dose isoniazid
Sponsored by
Stanford University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Tuberculosis Infection

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Federal University of Mato Grosso do SulRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Experimental

Arm Label

Rapid acetylator

Intermediate acetylator

Slow acetylator

Arm 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).

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

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

Outcomes

Primary Outcome Measures

Isoniazid plasma area-under-the-curve

Secondary Outcome Measures

Maximum isoniazid concentration (Cmax)
Isoniazid concentration at 24 hours

Full Information

First Posted
June 7, 2022
Last Updated
May 9, 2023
Sponsor
Stanford University
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID), Federal University of Mato Grosso, Fiocruz Mato Grosso do Sul
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1. Study Identification

Unique Protocol Identification Number
NCT05413551
Brief Title
Point-of-care Pharmacogenomic Testing to Optimize Isoniazid Dosing for Tuberculosis Prevention
Official Title
Point-of-care Pharmacogenomic Testing to Optimize Isoniazid Dosing for Tuberculosis Prevention
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 23, 2023 (Actual)
Primary Completion Date
December 1, 2023 (Anticipated)
Study Completion Date
April 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Stanford University
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID), Federal University of Mato Grosso, Fiocruz Mato Grosso do Sul

4. Oversight

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
Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis Infection, Isoniazid Adverse Reaction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
72 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Rapid acetylator
Arm Type
Experimental
Arm 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).
Arm Title
Intermediate acetylator
Arm Type
Active Comparator
Arm Description
Participants will receive 4 standard doses (Days 0, 7, 14 and 21).
Arm Title
Slow acetylator
Arm Type
Experimental
Arm 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).
Intervention Type
Drug
Intervention Name(s)
Low-dose isoniazid
Intervention Description
Pharmacogenomic-modified dose of isoniazid - 5 mg/kg oral tablet (maximum 300 mg)
Intervention Type
Drug
Intervention Name(s)
Standard dose of isoniazid
Intervention Description
15 mg/kg oral tablet (up to 900 mg)
Intervention Type
Drug
Intervention Name(s)
High-dose isoniazid
Intervention Description
Pharmacogenomic-modified dose of isoniazid - 25 mg/kg oral tablet (maximum 1500 mg)
Primary Outcome Measure Information:
Title
Isoniazid plasma area-under-the-curve
Time Frame
1, 2, 8, and 24 hours post-dose
Secondary Outcome Measure Information:
Title
Maximum isoniazid concentration (Cmax)
Time Frame
1, 2, 8, and 24 hours post-dose
Title
Isoniazid concentration at 24 hours
Time Frame
24 hours post-dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jason R Andrews, MD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Federal University of Mato Grosso do Sul
City
Campo Grande
State/Province
Mato Grosso Do Sul
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Julio Croda, MD, PhD
Phone
+55 67 3345-7223
Email
juliocroda@gmail.com

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
Citations:
PubMed Identifier
34375564
Citation
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.
Results Reference
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Point-of-care Pharmacogenomic Testing to Optimize Isoniazid Dosing for Tuberculosis Prevention

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