NCT00298870

Brief Summary

The purpose of this study is to elucidate whether the individualized medicine based on NAT2 gene polymorphism could improve the safety, efficacy and economical benefits of multi-drug therapy for the pulmonary tuberculosis with isoniazid.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
172

participants targeted

Target at P50-P75 for phase_4

Geographic Reach
1 country

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2005

Completed
9 months until next milestone

First Submitted

Initial submission to the registry

March 2, 2006

Completed
1 day until next milestone

First Posted

Study publicly available on registry

March 3, 2006

Completed
Last Updated

October 18, 2012

Status Verified

May 1, 2011

First QC Date

March 2, 2006

Last Update Submit

October 17, 2012

Conditions

Keywords

pulmonary tuberculosisisoniazidarylamine N-acetyltransferase 2pharmacogenomicsgenetic polymorphismsindividualized medicinedrug-induced hepatotoxity

Outcome Measures

Primary Outcomes (1)

  • The incidences of unfavorable events in two different treatment regimens based on the NAT2 gene polymorphism

    1\) the incidences of drug-induced liver injury associated with INH that occurred within 8 weeks of the treatments, and 2) the incidence of early treatment failure as indicated by a persistent positive culture or no improvement in chest radiographs at the 8th week

Secondary Outcomes (1)

  • Other adversed events during the 8 weeks of the intensive phase of the anti-tuberculosis therapy

Study Arms (2)

PGx-treatment

EXPERIMENTAL

NAT2 genotype-guided treatment with stratified isoniazid dose (approx. 7.5 mg/kg b.w., patients homozygous for NAT2\*4: rapid acetylators; 5 mg/kg, patients heterozygous for NAT2\*4: intermediate acetylators; 2.5 mg/kg, patientes without NAT2\*4: slow acetylators)

Drug: Isoniazid

STD-treatment

ACTIVE COMPARATOR

Treatment with conventional standard isoniazid dose (approx. 5 mg/kg b.w.)

Drug: isoniazed

Interventions

Modified daily isoniazid dose : approx. 7.5 mg/kg, 5 mg/kg and 2.5 mg/kg for rapid, intermediate and slow acetylators, respectively

PGx-treatment

Conventional standard daily isoniazid dose : approx. 5 mg/kg b.w. for all

STD-treatment

Eligibility Criteria

Age20 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Newly diagnosed pulmonary tuberculosis patients
  • Informed consent including pharmacogenomic analysis

You may not qualify if:

  • Abnormal liver and kidney function test before treatment
  • Long-term use of steroids and/or immunodepressants
  • Inadequate clinical conditions

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Osaka Prefectural Medical Center for Respiratory and Allergic Diseases

Habikino, Osaka, 583-8588, Japan

Location

Osaka Hospital, Anti-Tuberculosis Association, Osaka Branch

Neyagawa, Osaka, 572-0801, Japan

Location

National Hospital Organization Kinki-chuo Chest Medical Center

Sakai, Osaka, 591-8555, Japan

Location

National Hospital Organization Toneyama

Toyonaka, Osaka, 560-8552, Japan

Location

Related Publications (1)

  • Azuma J, Ohno M, Kubota R, Yokota S, Nagai T, Tsuyuguchi K, Okuda Y, Takashima T, Kamimura S, Fujio Y, Kawase I; Pharmacogenetics-based tuberculosis therapy research group. NAT2 genotype guided regimen reduces isoniazid-induced liver injury and early treatment failure in the 6-month four-drug standard treatment of tuberculosis: a randomized controlled trial for pharmacogenetics-based therapy. Eur J Clin Pharmacol. 2013 May;69(5):1091-101. doi: 10.1007/s00228-012-1429-9. Epub 2012 Nov 14.

MeSH Terms

Conditions

Tuberculosis, Pulmonary

Interventions

Isoniazid

Condition Hierarchy (Ancestors)

TuberculosisMycobacterium InfectionsActinomycetales InfectionsGram-Positive Bacterial InfectionsBacterial InfectionsBacterial Infections and MycosesInfectionsRespiratory Tract InfectionsLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

HydrazinesOrganic ChemicalsIsonicotinic AcidsAcids, HeterocyclicHeterocyclic CompoundsPyridinesHeterocyclic Compounds, 1-Ring

Study Officials

  • Junichi Azuma, MD

    Graduate School of Pharmaceutical Sciences, Osaka University

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

March 2, 2006

First Posted

March 3, 2006

Study Start

June 1, 2005

Last Updated

October 18, 2012

Record last verified: 2011-05

Locations