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Tuberculosis Treatment Shortening Trial

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00130247
First Posted: August 15, 2005
Last Update Posted: February 4, 2013
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
Results First Submitted: August 20, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (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 
Overall Participants Analyzed 
[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 ]
  Hide Outcome Measure 3

Measure Type Secondary
Measure Title Treatment Failures or Relapses at 2 Years After Completion of TB Treatment: Intention to Treat
Measure Description A culture-positive treatment failure was defined as initial culture conversion but subsequent reversion to culture positivity. A clinical treatment failure was defined as a patient with clinical and/or radiographic evidence of progressive tuberculosis not confirmed by a positive culture after 4 or more months of anti-TB treatment while still receiving treatment. Patients who defaulted before completing study treatment and returned later with culture-positive tuberculosis were termed failures after non-adherence.
Time Frame 2 years  

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.
The intention to treat (ITT) analysis included all 394 fully eligible and randomized patients allocated to the shortened 4-month treatment group (N=196) or the standard 6-month treatment group (N=198). There were no allocated patients excluded in the ITT analysis dataset.

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.

Measured Values
   4-Month Arm   6-Month Arm 
Participants Analyzed 
[Units: Participants]
 196   198 
Treatment Failures or Relapses at 2 Years After Completion of TB Treatment: Intention to Treat 
[Units: Participants]
   
Treatment Failures   0   0 
Relapses   13   3 

No statistical analysis provided for Treatment Failures or Relapses at 2 Years After Completion of TB Treatment: Intention to Treat



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 reported.   Anticipated Reporting Date:   No text entered.  

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 reported.   Anticipated Reporting Date:   No text entered.  

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 reported.   Anticipated Reporting Date:   No text entered.  

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 reported.   Anticipated Reporting Date:   No text entered.  

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 reported.   Anticipated Reporting Date:   No text entered.  


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Enrollment was stopped early and the number of patients enrolled was 1/2 of the original sample size. The study was completed.


  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
First Submitted: August 12, 2005
First Posted: August 15, 2005
Results First Submitted: August 20, 2009
Results First Posted: January 27, 2010
Last Update Posted: February 4, 2013