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
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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     164/198  
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