PROJECT

Shortened RegiMen for Drug-susceptIbLE TB in Children (SMILE-TB)

June 2026 - December 2030

Objectives:

To determine if an 8-week HPZM regimen in children with presumed drug-susceptible TB disease has non-inferior efficacy to 8-weeks of HRZ(E) plus 16-weeks of HR(E) for achieving treatment success.
To evaluate the safety of the 8-week HPZM regimen in comparison to the 24- week HRZ(E) regimen.

Study Overview:

SMILE-TB is an international clinical trial evaluating whether children aged 2 to <10 years with presumed drug-susceptible pulmonary or lymph node TB can be safely and effectively treated with a short 8-week regimen (HPZM) instead of the usual 16–24-week TB treatment. Children will be randomly assigned to either regimen and followed for 72 weeks to assess treatment success, safety, tolerability and adherence.

Study Approach:

This is an international, multicentre, randomized, controlled, open-label, Phase 3 non-inferiority trial in children aged 2 to <10 years with newly diagnosed, presumed drug-susceptible pulmonary and/or lymph node TB. A total of 160 children will be recruited in India and randomized 1:1 to receive either 8 weeks of HPZM (isoniazid, rifapentine, pyrazinamide and moxifloxacin) or the standard 24-week HRZ(E) regimen. Participants will be followed for 72 weeks after randomization, with clinical, laboratory, radiological, adherence, safety and treatment-response assessments.

Expected Public Health Impact:

If the 8-week HPZM regimen is shown to be as effective and safe as standard treatment, it could substantially shorten and simplify TB treatment in children, potentially improving treatment adherence and completion, reducing the burden on children and caregivers, and improving treatment outcomes.