Isoniazid Dosage Prediction Model Development

Development of a Dosing Model Based on Anti-tuberculosis Drug Monitoring NAT2 Genotypes in Tuberculosis Patients.

Isoniazid (INH) is an essential component of first-line anti-tuberculosis (TB) treatment. However, treatment with INH is complicated by polymorphisms in the expression of the enzyme system primarily responsible for its elimination, N-acetyltransferase 2 (NAT2), and its associated hepatotoxicity. The objective of this study was to develop an individualized INH dosing regimen using a pharmacogenetic-driven model and to apply this regimen in a pilot study.

Study Overview

• Status: Unknown
• Conditions: NAT2 Genotype
• Intervention / Treatment: Genetic: genotype

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Soo-Youn . Lee, MD; Phone Number: 82-2-3410-1834; Email: sy117.lee@samsung.com

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 135-710
    • Recruiting
    • Samsung Medical Center
    • Contact: Soo-Youn Lee

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 80 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

• Eligible participants were patients newly diagnosed with active TB
• Who underwent standard four drug treatment for 6months: isoniazid (5 mg/kg, usually 300 mg), rifampin (450 mg for <50 kg or 600 mg for 50 kg body weight), ethambutol(15mg/kg), and pyrazinamide (20 - 30 mg/kg)
• Given daily for two months and followed by isoniazid and rifampin with or without ethambutol for four months.
• Those patients with abnormal hepatic function on laboratory testing (increased serum aspartate aminotransferase, alanine aminotransferase, or total bilirubin) before anti-TB treatment, underlying liver disease or systemic illness such as congestive heart failure, acute life-threatening disease, or alcoholism, or disease that was resistant to INH at the start of treatment were excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: standard dosing; a standard treatment group; INH dose of 300 mg or 200 mg based on the body weight
EXPERIMENTAL: Genotype-guided dosing; INH dose determined based on developed model	Genetic: genotype; Patients were randomly assigned to a standard treatment group; INH dose of 300 mg or 200 mg based on the body weight) or model-based treatment group; INH dose determined based on developed model,

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Serum concentrations of INH	1 month

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Investigators: Principal Investigator: Soo-Youn Lee, MD, SMC

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (ANTICIPATED): December 1, 2016

Study Registration Dates

• First Submitted: April 19, 2016
• First Submitted That Met QC Criteria: April 21, 2016
• First Posted (ESTIMATE): April 22, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): April 22, 2016
• Last Update Submitted That Met QC Criteria: April 21, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: NAT2 genotype guided dosing
• Other Study ID Numbers: SMC-2013-07-155-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO