Tuberculosis Treatment Shortening Trial
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ClinicalTrials.gov Identifier: NCT00130247 |
Recruitment Status
:
Completed
First Posted
: August 15, 2005
Results First Posted
: January 27, 2010
Last Update Posted
: February 4, 2013
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Tuberculosis | Drug: Pyrazinamide Drug: Rifampin Drug: Isoniazid Drug: Ethambutol | Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 394 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Prospective Study of Shortening the Duration of Standard Short Course Chemotherapy From 6 Months to 4 Months in HIV-non-infected Patients With Fully Drug-Susceptible, Non-cavitary Pulmonary Tuberculosis With Negative Sputum Cultures After 2 Months of Anti-TB Treatment |
Study Start Date : | April 2002 |
Actual Primary Completion Date : | September 2008 |
Actual Study Completion Date : | November 2008 |

Arm | Intervention/treatment |
---|---|
Experimental: 2EHRZ/2HR arm
Daily treatment with isoniazid (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.
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Drug: Pyrazinamide
1st line bactericidal agent; dosages are 15-30 mg/kg/d, up to 2 grams (gm)/d.
Drug: Rifampin
1st line bactericidal agent which inhibits deoxyribonucleic acid (DNA)-dependent ribonucleic acid (RNA) polymerase; dosages are 10 mg/kg/d (up to 600 mg/d).
Drug: Isoniazid
Hydrazide of isonicotininc acid; antimicrobial activity is limited to mycobacteria where it inhibits the synthesis of mycolic acids.
Drug: Ethambutol
Mycobacteriostatic agent given to prevent emergence of drug resistance to other 1st line drugs; dosages are 15-25 milligram (mg)/ kilogram (kg)/day (d).
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Active Comparator: 2EHRZ/4HR arm
Daily treatment with Isoniazid (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.
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Drug: Pyrazinamide
1st line bactericidal agent; dosages are 15-30 mg/kg/d, up to 2 grams (gm)/d.
Drug: Rifampin
1st line bactericidal agent which inhibits deoxyribonucleic acid (DNA)-dependent ribonucleic acid (RNA) polymerase; dosages are 10 mg/kg/d (up to 600 mg/d).
Drug: Isoniazid
Hydrazide of isonicotininc acid; antimicrobial activity is limited to mycobacteria where it inhibits the synthesis of mycolic acids.
Drug: Ethambutol
Mycobacteriostatic agent given to prevent emergence of drug resistance to other 1st line drugs; dosages are 15-25 milligram (mg)/ kilogram (kg)/day (d).
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- Bacteriologic or Clinical Relapse at 30 Months After Onset of Initial Anti-tuberculosis (TB) Treatment - Intention-to-treat [ Time Frame: 30 months ]Patients who presented with TB after completion of study phase treatment but before the end of follow-up were classified as relapses. A bacteriologic relapse was defined as a patient who became consistently culture-positive [defined as at least 1 of the following]: (a) at least 1 sputum mycobacterial culture growing at least 10 colonies of MTB on solid medium; (b) 2 or more respiratory secretion cultures that are positive for MTB in liquid media; or (c) any culture from an extrapulmonary site that is positive for MTB during follow-up after successful completion of initial anti-TB treatment.
- Bacteriologic or Clinical Relapse at 30 Months After Onset of Initial Anti-TB Treatment - Per-protocol [ Time Frame: 30 months ]Patients who presented with TB after completion of study phase treatment but before the end of follow-up were classified as relapses. A bacteriologic relapse was defined as a patient who became consistently culture-positive [defined as at least 1 of the following]: (a) at least 1 sputum mycobacterial culture growing at least 10 colonies of MTB on solid medium; (b) 2 or more respiratory secretion cultures that are positive for MTB in liquid media; or (c) any culture from an extrapulmonary site that is positive for MTB during follow-up after successful completion of initial anti-TB treatment.
- Treatment Failures or Relapses at 2 Years After Completion of TB Treatment: Intention to Treat [ Time Frame: 2 years ]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.
- Treatment Failures or Relapses at 2 Years After Completion of TB Treatment: Per Protocol [ Time Frame: 2 years ]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.
- Relapses at 1 and 2 Years [ Time Frame: 1 and 2 years after successful completion of initial anti-TB treatment ]
- Acquired Drug Resistance in Patients Who Relapsed [ Time Frame: 2 years ]
- 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 ]
- 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 ]
- Immunologic: Changes in Sputum Cytokine Levels - Results Are Pending [ Time Frame: After 1 and 2 months of anti-TB treatment ]
- Microbiologic: Changes in Sputum Mycobacterial mRNA - Results Are Pending [ Time Frame: At 1 and 2 months of anti-TB treatment, and upon relapse ]
- 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 ]

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Ages Eligible for Study: | 18 Years to 60 Years (Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Adults, male or female, aged 18-60.
- Newly diagnosed initial episodes of pulmonary tuberculosis. Sputum smear-positive and -negative patients are eligible for enrollment. The diagnosis of tuberculosis must be confirmed by culture. Acid fast bacteria (AFB) smear positive patients found later not to have tuberculosis (TB) (i.e. those with non-tuberculous mycobacterial disease) and those without culture confirmation [at least one culture on solid media growing > 10 colonies of Mycobacterium tuberculosis (MTB) or a positive BACTEC or Mycobacteria growth indicator tube (MGIT) enriched liquid culture growing MTB] will be removed from the study.
- Chest X-ray and clinical findings consistent with tuberculosis.
- Hemoglobin greater than or equal to 8 gm/dL (greater than or equal to 5.0 mmol/L).
- Serum creatinine < 2 mg/dL (< 177 micro mol/L).
- Serum aspartate aminotransferase (AST) < 1.5 times the upper limit of normal for the testing laboratory, and serum total bilirubin < 1.3 mg/dL (22.2 micro mol/L).
- Random serum glucose less than or equal to 150 mg/dl (8.3 mmol/L).
- Ambulatory.
- Willing to provide informed consent for study participation, provide required specimens for examination, and to undergo and receive results of human immunodeficiency virus (HIV) testing.
- Willing to receive supervised anti-TB treatment.
- Completion of the required 112 doses of chemotherapy within 18 weeks of starting treatment.
Exclusion Criteria:
- Human immunodeficiency virus (HIV)-infected.
- History of prior tuberculosis or history of previous tuberculosis treatment.
- Pregnant or breastfeeding.
- Cavitary tuberculosis on initial chest X-ray (taken within 14 days of study entry).
- Exposure to person(s) with known drug resistant tuberculosis.
- Patients receiving chronic steroids or other immunosuppressive medications.
- Extra-pulmonary tuberculosis.
- Patients with drug resistant tuberculosis (resistance to isoniazid (INH), rifampicin, pyrazinamide or ethambutol).
- Professional sex worker, alcoholic and/or intravenous (IV) drug abuser.
- Silicosis or other serious chronic medical problems including diabetes mellitus or chronic renal failure.
Final determination of eligibility will be made after review of drug susceptibility testing results on an initial sputum isolate and results of all sputum cultures.
Pregnant patients may not be enrolled in the study. Patients in the 4 month arm who become pregnant during months 5 and 6 of study participation will be dropped from the study and receive an additional 2 months of treatment with INH and rifampicin.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00130247
Brazil | |
Universidade Federal do Espirito Santo/HUCAM | |
Vitoria, Brazil, 29040-091 | |
Philippines | |
Makati Medical Center | |
Makati City, Philippines, 1229 | |
Uganda | |
Tuberculosis Research Control Center, Mulago Hospital | |
Kampala, Uganda |
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 Posted: | August 15, 2005 Key Record Dates |
Results First Posted: | January 27, 2010 |
Last Update Posted: | February 4, 2013 |
Last Verified: | April 2010 |
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Tuberculosis, Uganda, Brazil, Philippines |
Additional relevant MeSH terms:
Tuberculosis Mycobacterium Infections Actinomycetales Infections Gram-Positive Bacterial Infections Bacterial Infections Rifampin Isoniazid Pyrazinamide Ethambutol Antibiotics, Antitubercular Antitubercular Agents Anti-Bacterial Agents Anti-Infective Agents Leprostatic Agents |
Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Cytochrome P-450 CYP2B6 Inducers Cytochrome P-450 Enzyme Inducers Cytochrome P-450 CYP2C8 Inducers Cytochrome P-450 CYP2C19 Inducers Cytochrome P-450 CYP2C9 Inducers Cytochrome P-450 CYP3A Inducers Fatty Acid Synthesis Inhibitors Hypolipidemic Agents Antimetabolites Lipid Regulating Agents |