Tuberculosis Treatment Shortening Trial

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00130247
First received: August 12, 2005
Last updated: January 31, 2013
Last verified: April 2010
Results First Received: August 20, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Tuberculosis
Interventions: Drug: Pyrazinamide
Drug: Rifampin
Drug: Isoniazid
Drug: Ethambutol

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
HIV-uninfected 18 to 60 year old adults with suspected or newly diagnosed pulmonary tuberculosis were eligible for enrollment at participating sites in Kampala, Uganda; Vitória, Brazil; and Manila/Makati City, the Philippines. Screening began in April 2002 in Uganda, December 2002 in Brazil, and November 2003 in the Philippines.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Subjects who met eligibility criteria were started on standard chemotherapy and routinely followed during anti-TB therapy. Patients with drug-susceptible TB who were sputum culture negative after 2 months of treatment were randomly assigned at 4 months to stop treatment or received an additional 2 months of daily isoniazid (INH) and rifampicin.

Reporting Groups
  Description
4-Month Arm Daily treatment with INH, rifampicin, ethambutol and pyrazinamide for 2 months followed by 2 months of daily INH plus rifampicin over a maximum time period of 18 weeks.
6-Month Arm Daily treatment with INH, rifampicin, ethambutol and pyrazinamide for 2 months followed by 4 months of daily INH plus rifampicin over a maximum time period of 28 weeks.

Participant Flow:   Overall Study
    4-Month Arm     6-Month Arm  
STARTED     196     198  
COMPLETED     194     194  
NOT COMPLETED     2     4  
Pregnancy                 1                 0  
Post-randomization exclusion                 1                 2  
Not compliant with DOT                 0                 2  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
4-Month Arm Daily treatment with INH, rifampicin, ethambutol and pyrazinamide for 2 months followed by 2 months of daily INH plus rifampicin over a maximum time period of 18 weeks.
6-Month Arm Daily treatment with INH, rifampicin, ethambutol and pyrazinamide for 2 months followed by 4 months of daily INH plus rifampicin over a maximum time period of 28 weeks.
Total Total of all reporting groups

Baseline Measures
    4-Month Arm     6-Month Arm     Total  
Number of Participants  
[units: participants]
  196     198     394  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     196     198     394  
>=65 years     0     0     0  
Age  
[units: years]
Mean ± Standard Deviation
  31.2  ± 10     30.3  ± 10     30.8  ± 10  
Gender  
[units: participants]
     
Female     77     78     155  
Male     119     120     239  
Region of Enrollment  
[units: participants]
     
Philippines     47     48     95  
Brazil     81     81     162  
Uganda     68     69     137  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Bacteriologic or Clinical Relapse at 30 Months After Onset of Initial Anti-tuberculosis (TB) Treatment - Intention-to-treat   [ Time Frame: 30 months ]

2.  Primary:   Bacteriologic or Clinical Relapse at 30 Months After Onset of Initial Anti-TB Treatment - Per-protocol   [ Time Frame: 30 months ]

3.  Secondary:   Treatment Failures or Relapses at 2 Years After Completion of TB Treatment: Intention to Treat   [ Time Frame: 2 years ]

4.  Secondary:   Treatment Failures or Relapses at 2 Years After Completion of TB Treatment: Per Protocol   [ Time Frame: 2 years ]

5.  Secondary:   Relapses at 1 and 2 Years   [ Time Frame: 1 and 2 years after successful completion of initial anti-TB treatment ]

6.  Secondary:   Acquired Drug Resistance in Patients Who Relapsed   [ Time Frame: 2 years ]

7.  Secondary:   Immunologic: Changes in Cytokine Levels in Mycobacterium Tubercolosis (MTB) Antigen-stimulated Whole Blood Culture Supernatants - Results Are Pending   [ Time Frame: After 2 and 6 months of anti-TB treatment and upon relapse ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

8.  Secondary:   Immunologic: Store Peripheral Blood Mononuclear Cells (PBMC) - Results Are Pending   [ Time Frame: Pre-treatment and serum pre-treatment after 2 and 6 months of anti-TB treatment, and at the time of relapse for future immunologic analysis ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

9.  Secondary:   Immunologic: Changes in Sputum Cytokine Levels - Results Are Pending   [ Time Frame: After 1 and 2 months of anti-TB treatment ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

10.  Secondary:   Microbiologic: Changes in Sputum Mycobacterial mRNA - Results Are Pending   [ Time Frame: At 1 and 2 months of anti-TB treatment, and upon relapse ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

11.  Secondary:   Microbiologic: Time After Inoculation Until Culture Positive in BACTEC 460 or MGIT 960 Enriched Liquid Media After 2 Months in Treatment - Results Are Pending   [ Time Frame: Months 1, 2, 3, 4, 5, 6, 9, 12, 15, 18, 24, and 30 ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: John L. Johnson, M.D., Principal Investigator
Organization: Case Western Reserve University, Tuberculosis Research Unit
phone: (216) 368-1949
e-mail: jlj@case.edu


Publications of Results:
Other Publications:

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00130247     History of Changes
Other Study ID Numbers: 01-009, TBRU 8
Study First Received: August 12, 2005
Results First Received: August 20, 2009
Last Updated: January 31, 2013
Health Authority: United States: Food and Drug Administration
United States: Federal Government
United States: Institutional Review Board
Philippines: Institutional Review Board or Ethics Committee of Makerere University
Uganda: Institutional Review Board