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TuberculosisPhase 3NCT00130247

Tuberculosis Treatment Shortening Trial

A Phase 3 study testing Ethambutol, Isoniazid and Pyrazinamide in people with Tuberculosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Tuberculosis (TB) is a serious infection that can affect the lungs and other parts of the body. The usual way to treat TB is to take 4 medicines by mouth every day for 2 months, then take 2 of the same medicines for 4 more months, for a total of 6 months. Read more about this study

Who is it for?
Ages 18 to 60 years
Conditions the study is for
Tuberculosis
What is being tested?
Ethambutol, Isoniazid and Pyrazinamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
394 participants
Where
3 sitesin 3 countries
Study dates
8 Apr 2002to 28 Nov 2008
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • -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.

Who cannot join

  • -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.

Trial locations and contacts

3 sites in 3 countries.

3 sites in 3 countries

Brazil1 site

  • Universidade Federal do Espirito Santo - Duke Hubert-Yeargan Center

    Vitória, Espírito Santo, 29040-091

Other trials in Brazil

Philippines1 site

  • Makati Medical Center

    Makati City, National Capital Region, 1229

Other trials in Philippines

Uganda1 site

  • Mulago Hospital Complex

    Kampala, 99999

Other trials in Uganda

About this study

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

Tuberculosis (TB) is a serious infection that can affect the lungs and other parts of the body. The usual way to treat TB is to take 4 medicines by mouth every day for 2 months, then take 2 of the same medicines for 4 more months, for a total of 6 months. The purpose of this study is to see if taking 4 months of TB medicines is as effective in curing some TB patients as taking 6 months of TB medicines. Study participants will include 758 human immunodeficiency virus (HIV)-non-infected individuals, ages 18-60. Participants will be treated with 4 standard drugs called isoniazid, rifampicin, pyrazinamide and ethambutol. All individuals will take TB medicines for at least 4 months. After 4 months of treatment, if no TB germs are growing in sputum samples, participants will be assigned to either stop taking TB medicine (4 months of treatment) or to continue taking TB drugs for 2 more months (6 months of treatment). Participants will be involved in study procedures for up to 30 months.

Read the detailed description

Tuberculosis (TB) is a major global health problem. TB is the current leading cause of death due to an identifiable infectious agent worldwide. One of the highest priorities for tuberculosis control programs is to shorten anti-TB treatment while maintaining its effectiveness. Current 6-month short course chemotherapy regimens are over 95% effective for the treatment of tuberculosis when fully administered. Six months is a long time, however, and patients frequently discontinue anti-TB treatment once their symptoms have improved. The duration of standard short course chemotherapy is one of the major obstacles to its successful application and poses substantial challenges to programs with respect to patient adherence, program resource needs, and logistical requirements for directly observed therapy. The primary objective of this study is to assess the efficacy of shortening anti-TB treatment to 4 months in human immunodeficiency virus (HIV)-non-infected adults with drug-susceptible, non-cavitary pulmonary tuberculosis who convert their sputum culture to negative after 2 months of treatment. Secondary objectives of this study include: comparing pre-treatment sputum bacillary load in patients with and without cavitary disease; compare time after inoculation of BACTEC or Mycobacteria growth indicator tube (MGIT) liquid culture media until positive with semi-quantitative sputum acid fast bacteria (AFB) smear and culture on solid media as measures of pre-treatment sputum bacillary load; and determining the influence of immunologic characteristics of subjects pre-treatment, during treatment and at the end of therapy on rate of bacillary clearance and risk for relapse. A total of 758 HIV-non-infected adults, male or female, 18-60 years of age, with newly diagnosed initial episodes of sputum AFB smear-positive or -negative, culture-positive, non-cavitary, drug-susceptible pulmonary TB who are sputum culture negative after 2 months of anti-TB treatment will be randomly assigned to complete a total of 4 or 6 months of anti-TB therapy. The experimental regimen will include a total of 4 months of anti-TB treatment [2 months of daily isoniazid (INH), rifampicin, pyrazinamide and ethambutol followed by 2 months of daily INH and rifampicin]. The comparative regimen will include a total of 6 months standard short course anti-TB chemotherapy (2 months of daily INH, rifampicin, pyrazinamide and ethambutol followed by 4 months of daily INH and rifampicin). Subjects will be involved in study related procedures for approximately 30 months after beginning the initial anti-TB treatment.

Conditions
Tuberculosis
Being tested
Ethambutol, Isoniazid, Pyrazinamide, Rifampin
Keywords
Brazil, Philippines, Tuberculosis, Uganda
Medical subject headings
Tuberculosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EthambutolDrug

    Mycobacteriostatic agent given to prevent emergence of drug resistance to other 1st line drugs; dosages are 15-25 milligram (mg)/ kilogram (kg)/day (d).

  • IsoniazidDrug

    Hydrazide of isonicotininc acid; antimicrobial activity is limited to mycobacteria where it inhibits the synthesis of mycolic acids.

  • PyrazinamideDrug

    1st line bactericidal agent; dosages are 15-30 mg/kg/d, up to 2 grams (gm)/d.

  • RifampinDrug

    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).

Study groups in NCT00130247
Study groupRoleWhat they receive
2EHRZ/2HR armExperimentalDaily 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.
Receives: Drug: Ethambutol; Drug: Isoniazid; Drug: Pyrazinamide; Drug: Rifampin
2EHRZ/4HR armActive comparatorDaily 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.
Receives: Drug: Ethambutol; Drug: Isoniazid; Drug: Pyrazinamide; Drug: Rifampin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Bacteriologic or Clinical Relapse at 30 Months After Onset of Initial Anti-tuberculosis (TB) Treatment - Intention-to-treat

    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.

    Measured: 30 months

  2. Bacteriologic or Clinical Relapse at 30 Months After Onset of Initial Anti-TB Treatment - Per-protocol

    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.

    Measured: 30 months

Secondary outcomes (9)

  1. Treatment Failures or Relapses at 2 Years After Completion of TB Treatment: Intention to Treat

    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.

    Measured: 2 years

  2. Treatment Failures or Relapses at 2 Years After Completion of TB Treatment: Per Protocol

    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.

    Measured: 2 years

  3. Relapses at 1 and 2 Years

    Measured: 1 and 2 years after successful completion of initial anti-TB treatment

  4. Acquired Drug Resistance in Patients Who Relapsed

    Measured: 2 years

  5. Immunologic: Changes in Cytokine Levels in Mycobacterium Tuberculosis (MTB) Antigen-stimulated Whole Blood Culture Supernatants

    Measured: After 2 and 6 months of anti-TB treatment and upon relapse

  6. Immunologic: Store Peripheral Blood Mononuclear Cells (PBMC)

    Measured: 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

  7. Immunologic: Changes in Sputum Cytokine Levels

    Measured: After 1 and 2 months of anti-TB treatment

  8. Microbiologic: Changes in Sputum Mycobacterial mRNA

    Measured: At 1 and 2 months of anti-TB treatment, and upon relapse

  9. Microbiologic: Time After Inoculation Until Culture Positive in BACTEC 460 or MGIT 960 Enriched Liquid Media After 2 Months in Treatment

    Measured: Months 1, 2, 3, 4, 5, 6, 9, 12, 15, 18, 24, and 30

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Aug 2005 (estimated)
  2. Study start8 Apr 2002
  3. Primary completion2 Sep 2008
  4. Study completion28 Nov 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
394 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00130247
Sponsor's protocol ID
01-009
Status last verified
20 Apr 2010
First submitted
12 Aug 2005
Last updated
15 Oct 2026
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Johnson JL, Thiel BA. Time until relapse in tuberculosis treatment trials: implication for phase 3 trial design. Am J Respir Crit Care Med. 2012 Sep 1;186(5):464. doi: 10.1164/ajrccm.186.5.464. No abstract available.

    PubMed 22942350

  • Palaci M, Dietze R, Hadad DJ, Ribeiro FK, Peres RL, Vinhas SA, Maciel EL, do Valle Dettoni V, Horter L, Boom WH, Johnson JL, Eisenach KD. Cavitary disease and quantitative sputum bacillary load in cases of pulmonary tuberculosis. J Clin Microbiol. 2007 Dec;45(12):4064-6. doi: 10.1128/JCM.01780-07. Epub 2007 Oct 10.

    PubMed 17928422

  • Bark CM, Dietze R, Okwera A, Quelapio MI, Thiel BA, Johnson JL. Clinical symptoms and microbiological outcomes in tuberculosis treatment trials. Tuberculosis (Edinb). 2011 Nov;91(6):601-4. doi: 10.1016/j.tube.2011.05.007. Epub 2011 Aug 2.

    PubMed 21813327

  • Colangeli R, Jedrey H, Kim S, Connell R, Ma S, Chippada Venkata UD, Chakravorty S, Gupta A, Sizemore EE, Diem L, Sherman DR, Okwera A, Dietze R, Boom WH, Johnson JL, Mac Kenzie WR, Alland D; DMID 01-009/Tuberculosis Trials Consortium Study 22 Teams. Bacterial Factors That Predict Relapse after Tuberculosis Therapy. N Engl J Med. 2018 Aug 30;379(9):823-833. doi: 10.1056/NEJMoa1715849.

    PubMed 30157391

  • Bark CM, Thiel BA, Johnson JL. Pretreatment time to detection of Mycobacterium tuberculosis in liquid culture is associated with relapse after therapy. J Clin Microbiol. 2012 Feb;50(2):538. doi: 10.1128/JCM.06193-11. Epub 2011 Nov 23. No abstract available.

    PubMed 22116143

  • Johnson JL, Hadad DJ, Dietze R, Maciel EL, Sewali B, Gitta P, Okwera A, Mugerwa RD, Alcaneses MR, Quelapio MI, Tupasi TE, Horter L, Debanne SM, Eisenach KD, Boom WH. Shortening treatment in adults with noncavitary tuberculosis and 2-month culture conversion. Am J Respir Crit Care Med. 2009 Sep 15;180(6):558-63. doi: 10.1164/rccm.200904-0536OC. Epub 2009 Jun 19.

    PubMed 19542476

  • Maciel EL, Brioschi AP, Peres RL, Guidoni LM, Ribeiro FK, Hadad DJ, Vinhas SA, Zandonade E, Palaci M, Dietze R, Johnson JL. Smoking and 2-month culture conversion during anti-tuberculosis treatment. Int J Tuberc Lung Dis. 2013 Feb;17(2):225-8. doi: 10.5588/ijtld.12.0426.

    PubMed 23317958

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ethambutol, Isoniazid and Pyrazinamide in people with Tuberculosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Brazil, Philippines, Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Jan 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Bacteriologic or Clinical Relapse at 30 Months After Onset of Initial Anti-tuberculosis (TB) Treatment - Intention-to-treat (time frame: 30 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00130247, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2026.

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