Doxycycline Host-directed Therapy to Improve Lung Function and Decrease Tissue Destruction in Pulmonary Tuberculosis

Tuberculosis (TB) is a global pandemic that despite successful treatment and bacterial eradication can cause chronic ill health, also known as pulmonary impairment after tuberculosis (PIAT). A recent Phase 2b double-blind randomised-controlled clinical trial shows that adjunctive doxycycline therapy along with standard pulmonary TB (PTB) treatment is safe, accelerates resolution of inflammation, suppresses tissue damaging enzyme activity and decreases pulmonary cavity volume (1). The investigators aim to determine if adjunctive doxycycline can reduce PIAT in a fully powered Phase III trial of 8 weeks of adjunctive doxycycline alongside standard pulmonary TB treatment. The investigators hypothesize that doxycycline inhibits tissue destruction in patients with pulmonary tuberculosis (PTB) and thereby leads to improved lung function after treatment. Specific aims 1. To assess for improvement in lung function as measured by forced expiratory volume (FEV1) predicted in PTB patients given doxycycline versus placebo. 2. To investigate whether doxycycline will hasten the resolution of pulmonary cavities measured by CT thorax, suppress inflammatory markers including matrix metalloproteinases and accelerate time to sputum culture conversion. 3. To assess the safety profile of doxycycline with concurrent standard anti-tuberculous treatment.