Tuberculosis Treatment Shortening Trial
Condition: Tuberculosis
MeSH terms: Tuberculosis
Intervention: Ethambutol; Isoniazid; Pyrazinamide; Rifampin
Intervention description: Mycobacteriostatic agent given to prevent emergence of drug resistance to other 1st line drugs; dosages are 15-25 milligram (mg)/ kilogram (kg)/day (d).; Hydrazide of isonicotininc acid; antimicrobial activity is limited to mycobacteria where it inhibits the synthesis of mycolic acids.; 1st line bactericidal agent; dosages are 15-30 mg/kg/d, up to 2 grams (gm)/d.; 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).
Intervention MeSH terms: Rifampin; Isoniazid; Pyrazinamide; Ethambutol
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 394.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Brazil; Philippines; Tuberculosis; Uganda

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. 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.
    

Eligibility criteria:

        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.