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

Primary Purpose

Pulmonary Tuberculosis

Status
Completed
Phase
Phase 4
Locations
Japan
Study Type
Interventional
Intervention
Isoniazid
isoniazed
Sponsored by
Osaka University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Tuberculosis focused on measuring pulmonary tuberculosis, isoniazid, arylamine N-acetyltransferase 2, pharmacogenomics, genetic polymorphisms, individualized medicine, drug-induced hepatotoxity

Eligibility Criteria

20 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Osaka Prefectural Medical Center for Respiratory and Allergic Diseases
  • Osaka Hospital, Anti-Tuberculosis Association, Osaka Branch
  • National Hospital Organization Kinki-chuo Chest Medical Center
  • National Hospital Organization Toneyama

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

PGx-treatment

STD-treatment

Arm Description

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)

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

Outcomes

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

Full Information

First Posted
March 2, 2006
Last Updated
October 17, 2012
Sponsor
Osaka University
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1. Study Identification

Unique Protocol Identification Number
NCT00298870
Brief Title
Randomized Trial for Pharmacogenomics-based Tuberculosis Therapy (RT-PGTT)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2011
Overall Recruitment Status
Completed
Study Start Date
June 2005 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Osaka University

4. Oversight

Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Tuberculosis
Keywords
pulmonary tuberculosis, isoniazid, arylamine N-acetyltransferase 2, pharmacogenomics, genetic polymorphisms, individualized medicine, drug-induced hepatotoxity

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
172 (Actual)

8. Arms, Groups, and Interventions

Arm Title
PGx-treatment
Arm Type
Experimental
Arm Description
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)
Arm Title
STD-treatment
Arm Type
Active Comparator
Arm Description
Treatment with conventional standard isoniazid dose (approx. 5 mg/kg b.w.)
Intervention Type
Drug
Intervention Name(s)
Isoniazid
Intervention Description
Modified daily isoniazid dose : approx. 7.5 mg/kg, 5 mg/kg and 2.5 mg/kg for rapid, intermediate and slow acetylators, respectively
Intervention Type
Drug
Intervention Name(s)
isoniazed
Intervention Description
Conventional standard daily isoniazid dose : approx. 5 mg/kg b.w. for all
Primary Outcome Measure Information:
Title
The incidences of unfavorable events in two different treatment regimens based on the NAT2 gene polymorphism
Description
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 Measure Information:
Title
Other adversed events during the 8 weeks of the intensive phase of the anti-tuberculosis therapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Junichi Azuma, MD
Organizational Affiliation
Graduate School of Pharmaceutical Sciences, Osaka University
Official's Role
Study Chair
Facility Information:
Facility Name
Osaka Prefectural Medical Center for Respiratory and Allergic Diseases
City
Habikino
State/Province
Osaka
ZIP/Postal Code
583-8588
Country
Japan
Facility Name
Osaka Hospital, Anti-Tuberculosis Association, Osaka Branch
City
Neyagawa
State/Province
Osaka
ZIP/Postal Code
572-0801
Country
Japan
Facility Name
National Hospital Organization Kinki-chuo Chest Medical Center
City
Sakai
State/Province
Osaka
ZIP/Postal Code
591-8555
Country
Japan
Facility Name
National Hospital Organization Toneyama
City
Toyonaka
State/Province
Osaka
ZIP/Postal Code
560-8552
Country
Japan

12. IPD Sharing Statement

Citations:
PubMed Identifier
23150149
Citation
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.
Results Reference
derived

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

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