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

Purpose

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	Intervention	Phase
Pulmonary Tuberculosis	Drug: Isoniazid Drug: isoniazed	Phase 4


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment

Resource links provided by NLM:

MedlinePlus related topics: Tuberculosis

Drug Information available for: Isoniazid

Genetic and Rare Diseases Information Center resources: Tuberculosis

U.S. FDA Resources

Further study details as provided by Osaka University:

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


Enrollment:	172
Study Start Date:	June 2005

Arms	Assigned Interventions
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

Eligibility


Ages Eligible for Study:	20 Years to 75 Years
Genders Eligible for Study:	Both
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00298870

Locations


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


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

More Information

No publications provided by Osaka University

Additional 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.


ClinicalTrials.gov Identifier:	NCT00298870 History of Changes
Other Study ID Numbers:	PG-MRT-TB-01
Study First Received:	March 2, 2006
Last Updated:	October 17, 2012
Health Authority:	Japan: Ministry of Health, Labor and Welfare

Keywords provided by Osaka University:


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

Additional relevant MeSH terms:


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

ClinicalTrials.gov processed this record on February 25, 2015