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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 
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 ]

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.   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 reported.   Anticipated Reporting 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 reported.   Anticipated Reporting 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 reported.   Anticipated Reporting 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 reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events
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Time Frame 6 years
Additional Description Patients reported adverse events at scheduled or unscheduled visits. Adverse event forms were completed by medical officers on site

Frequency Threshold
Threshold above which other adverse events are reported   5  

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.

Other Adverse Events
    4-Month Arm   6-Month Arm
Total, other (not including serious) adverse events     
# participants affected / at risk   170/196 (86.73%)   164/198 (82.83%) 
Blood and lymphatic system disorders     
Hemoptysis † 1     
# participants affected / at risk   15/196 (7.65%)   15/198 (7.58%) 
# events   19   19 
Gastrointestinal disorders     
Abdominal Pain † 1     
# participants affected / at risk   48/196 (24.49%)   49/198 (24.75%) 
# events   63   59 
Diarrhea † 1     
# participants affected / at risk   15/196 (7.65%)   10/198 (5.05%) 
# events   20   10 
Nausea † 1     
# participants affected / at risk   20/196 (10.20%)   32/198 (16.16%) 
# events   31   41 
Vomiting † 1     
# participants affected / at risk   15/196 (7.65%)   16/198 (8.08%) 
# events   18   19 
General disorders     
Fever † 1     
# participants affected / at risk   87/196 (44.39%)   67/198 (33.84%) 
# events   148   103 
Malaise † 1     
# participants affected / at risk   17/196 (8.67%)   15/198 (7.58%) 
# events   22   18 
Rigors † 1     
# participants affected / at risk   13/196 (6.63%)   12/198 (6.06%) 
# events   15   15 
Sweating † 1     
# participants affected / at risk   13/196 (6.63%)   17/198 (8.59%) 
# events   15   22 
Infections and infestations     
Flu † 1     
# participants affected / at risk   40/196 (20.41%)   27/198 (13.64%) 
# events   63   46 
Malaria † 1     
# participants affected / at risk   9/196 (4.59%)   2/198 (1.01%) 
# events   12   3 
Tinea Infection † 1     
# participants affected / at risk   10/196 (5.10%)   6/198 (3.03%) 
# events   12   9 
Metabolism and nutrition disorders     
Appetite Lost † 1     
# participants affected / at risk   39/196 (19.90%)   30/198 (15.15%) 
# events   49   35 
Weight Loss † 1     
# participants affected / at risk   24/196 (12.24%)   20/198 (10.10%) 
# events   29   26 
Musculoskeletal and connective tissue disorders     
Arthralgia † 2     
# participants affected / at risk   64/196 (32.65%)   64/198 (32.32%) 
# events   92   87 
Back Pain † 1     
# participants affected / at risk   34/196 (17.35%)   31/198 (15.66%) 
# events   46   36 
Myalgia † 1     
# participants affected / at risk   5/196 (2.55%)   15/198 (7.58%) 
# events   5   16 
Pain in Limb † 1     
# participants affected / at risk   6/196 (3.06%)   11/198 (5.56%) 
# events   8   14 
Nervous system disorders     
Dizziness † 1     
# participants affected / at risk   18/196 (9.18%)   17/198 (8.59%) 
# events   20   18 
Headache † 1     
# participants affected / at risk   64/196 (32.65%)   46/198 (23.23%) 
# events   102   66 
Psychiatric disorders     
Insomnia † 1     
# participants affected / at risk   8/196 (4.08%)   11/198 (5.56%) 
# events   11   15 
Respiratory, thoracic and mediastinal disorders     
Chest Pain † 1     
# participants affected / at risk   70/196 (35.71%)   52/198 (26.26%) 
# events   115   77 
Coryza † 1     
# participants affected / at risk   11/196 (5.61%)   10/198 (5.05%) 
# events   11   11 
Cough † 1     
# participants affected / at risk   104/196 (53.06%)   90/198 (45.45%) 
# events   186   162 
Dyspnea † 1     
# participants affected / at risk   17/196 (8.67%)   9/198 (4.55%) 
# events   18   9 
Produce Sputum † 1     
# participants affected / at risk   48/196 (24.49%)   39/198 (19.70%) 
# events   57   50 
Purulent Sputum † 1     
# participants affected / at risk   34/196 (17.35%)   27/198 (13.64%) 
# events   40   33 
Rhinorrhea † 1     
# participants affected / at risk   12/196 (6.12%)   17/198 (8.59%) 
# events   17   19 
Sore Throat † 1     
# participants affected / at risk   14/196 (7.14%)   10/198 (5.05%) 
# events   15   10 
Upper Respiratory Tract Infection † 1     
# participants affected / at risk   33/196 (16.84%)   27/198 (13.64%) 
# events   50   39 
Skin and subcutaneous tissue disorders     
Acne † 1     
# participants affected / at risk   14/196 (7.14%)   16/198 (8.08%) 
# events   15   17 
Pruritis † 1     
# participants affected / at risk   46/196 (23.47%)   43/198 (21.72%) 
# events   57   52 
Rash † 1     
# participants affected / at risk   18/196 (9.18%)   15/198 (7.58%) 
# events   20   15 
Skin Lesion † 1     
# participants affected / at risk   15/196 (7.65%)   9/198 (4.55%) 
# events   21   22 
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA (10.1)
2 Term from vocabulary, MedDRA 10.1



  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
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