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

Tuberculosis Clinical Trial

Official title: Doxycycline Host-directed Therapy to Improve Lung Function and Decrease Tissue Destruction in Pulmonary Tuberculosis: A Phase III Randomized Control Trial (Doxy-TB)

Status Recruiting

Clinical Trial Summary

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.

Clinical Trial Description

In this Phase 3 double-blind randomised-controlled trial, doxycycline or placebo shall be given to 75 PTB patients in each arm for two months with a further follow-up of four months. Study sites are National University Hospital and TB Control Unit in Singapore and Luyang Health Clinic, Menggatal Health Clinic, and Inanam Health Clinic in Sabah, Malaysia. Lung function tests and non-contrast CT thorax will be performed at various time intervals. Induced sputum and plasma samples from all PTB patients shall be analysed for matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs) and monitored for sputum mycobacteria culture conversion. Whole blood will be analysed by transcriptomics for bulk RNAseq while a subset of patients' blood will be analysed using single-cell RNAsequencing. Accomplishing these specific aims will determine if doxycycline decreases PIAT by improving lung function, reducing pulmonary cavities and accelerating sputum culture conversion. The results will positively impact clinical practice and international guidelines including the World Health Organisation that we collaborate with, for the treatment of pulmonary TB. ;

Related Conditions & MeSH terms

• Tuberculosis
• Tuberculosis, Pulmonary

• NCT number: NCT05473520
• Study type: Interventional
• Source: National University Hospital, Singapore
• Contact: Srishti CHHABRA, MBBS
• Phone: +65 6908 2222
• Email: Srishti_CHHABRA@nuhs.edu.sg
• Status: Recruiting
• Phase: Phase 3
• Start date: May 24, 2023
• Completion date: January 27, 2027