Randomized Trial for Pharmacogenomics-based Tuberculosis Therapy (RT-PGTT)

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ClinicalTrials.gov Identifier: NCT00298870

Recruitment Status : Completed

First Posted : March 3, 2006

Last Update Posted : October 18, 2012

Sponsor:

Information provided by:

Osaka University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Pulmonary Tuberculosis	Drug: Isoniazid Drug: isoniazed	Phase 4

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	172 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Study Start Date :	June 2005

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Tuberculosis

Drug Information available for: Isoniazid

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: PGx-treatment NAT2 genotype-guided treatment with stratified isoniazid dose (approx. 7.5 mg/kg b.w., patients homozygous for NAT24: rapid acetylators; 5 mg/kg, patients heterozygous for NAT24: intermediate acetylators; 2.5 mg/kg, patientes without NAT2*4: slow acetylators)	Drug: Isoniazid Modified daily isoniazid dose : approx. 7.5 mg/kg, 5 mg/kg and 2.5 mg/kg for rapid, intermediate and slow acetylators, respectively
Active Comparator: STD-treatment Treatment with conventional standard isoniazid dose (approx. 5 mg/kg b.w.)	Drug: isoniazed Conventional standard daily isoniazid dose : approx. 5 mg/kg b.w. for all

Outcome Measures

Primary Outcome Measures :

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 Outcome Measures :

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

Eligibility Criteria

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Ages Eligible for Study:	20 Years to 75 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Newly diagnosed pulmonary tuberculosis patients
Informed consent including pharmacogenomic analysis

Exclusion Criteria:

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

Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00298870

Locations

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Japan
Osaka Prefectural Medical Center for Respiratory and Allergic Diseases
Habikino, Osaka, Japan, 583-8588
Osaka Hospital, Anti-Tuberculosis Association, Osaka Branch
Neyagawa, Osaka, Japan, 572-0801
National Hospital Organization Kinki-chuo Chest Medical Center
Sakai, Osaka, Japan, 591-8555
National Hospital Organization Toneyama
Toyonaka, Osaka, Japan, 560-8552

Sponsors and Collaborators

Osaka University

Investigators

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Study Chair:	Junichi Azuma, MD	Graduate School of Pharmaceutical Sciences, Osaka University

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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ClinicalTrials.gov Identifier:	NCT00298870
Other Study ID Numbers:	PG-MRT-TB-01
First Posted:	March 3, 2006 Key Record Dates
Last Update Posted:	October 18, 2012
Last Verified:	May 2011

Keywords provided by Osaka University:


pulmonary tuberculosis isoniazid arylamine N-acetyltransferase 2 pharmacogenomics	genetic polymorphisms individualized medicine drug-induced hepatotoxity

Additional relevant MeSH terms:

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Tuberculosis Tuberculosis, Pulmonary Mycobacterium Infections Actinomycetales Infections Gram-Positive Bacterial Infections Bacterial Infections Lung Diseases Respiratory Tract Diseases Respiratory Tract Infections	Isoniazid Antitubercular Agents Anti-Bacterial Agents Anti-Infective Agents Fatty Acid Synthesis Inhibitors Hypolipidemic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Lipid Regulating Agents

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