Tuberculosis Treatment Shortening Trial
Condition: Tuberculosis
MeSH terms: Tuberculosis
Study type: Interventional
Phase: Phase 3

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.
    

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.
    

Intervention name(s): Ethambutol; Isoniazid; Pyrazinamide; Rifampin
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 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
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Brazil; Philippines; Tuberculosis; Uganda