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
Location: See all (6) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 3
SUMMARY

Tuberculosis (TB) is a global pandemic that despite successful treatment and bacterial eradication can cause chronic ill health, such as pulmonary impairment after tuberculosis (PIAT) and cardiovascular disease (CVD). A recent Phase 2b double-blind randomised-controlled clinical trial shows that adjunctive doxycycline therapy is safe, accelerates resolution of inflammation, suppresses tissue damaging enzyme activity and decreases pulmonary cavity volume (1). We aim to determine if adjunctive doxycycline can reduce PIAT and improve cardiovascular outcomes in a fully powered Phase III trial of 8 weeks of adjunctive doxycycline alongside standard pulmonary TB (PTB) treatment. The investigators hypothesize that doxycycline inhibits tissue destruction in patients with PTB and thereby leads to improved lung function after treatment. Specific aims 1. To assess 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 3. To investigate whether doxycycline can suppress inflammatory markers including matrix metalloproteinases 4. To investigate whether doxycycline can accelerate time to sputum conversion 5. To evaluate the effect of doxycycline on cardiovascular outcomes such as the incidence of acute coronary syndrome (ACS) and pulmonary hypertension 6. To investigate whether doxycycline improves TB drug concentrations in sputum and plasma. 7. To assess the safety profile of doxycycline with concurrent standard anti-tuberculous treatment.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 21
Healthy Volunteers: f
View:

• Aged 21 years and above

• Patients receiving ≤ 7 days of TB treatment or about to start standard combination TB treatment

• Confirmed pulmonary TB with positive acid-fast bacilli smear and/or positive nucleic acid amplification test (NAAT) and/or TB culture results

• CXR demonstrating pulmonary involvement with cavity or cavities

• Able to provide informed consent

Locations
Other Locations
Malaysia
Hospital Queen Elizabeth I
NOT_YET_RECRUITING
Kota Kinabalu
Klinik Kesihatan Luyang
ACTIVE_NOT_RECRUITING
Kota Kinabalu
Klinik Kesihatan Menggatal
RECRUITING
Kota Kinabalu
Universiti Malaysia Sabah (UMS), Borneo Medical and Health Research Centre
ACTIVE_NOT_RECRUITING
Kota Kinabalu
Singapore
National University Hospital
RECRUITING
Singapore
TB Control Unit
RECRUITING
Singapore
Contact Information
Primary
Srishti CHHABRA, MBBS BSc MRCP
srishti.chhabra@mohh.com.sg
+65 6908 2222
Time Frame
Start Date: 2023-05-24
Estimated Completion Date: 2030-01-31
Participants
Target number of participants: 150
Treatments
Experimental: Doxycycline + standard anti-tuberculous treatment
Doxycycline 100 mg twice daily with once daily anti-tuberculous treatment comprising of rifampicin 10 mg/kg, isoniazid 5 mg/kg, ethambutol 15 - 20 mg/kg, ± pyrazinamide 25 mg/kg and pyridoxine 10-50 mg per day according to managing physicians' discretion. Where needed, the drugs will be adjusted according to renal function. These will be given daily for 8 weeks. Subsequently doxycycline will be ceased and patients are to continue with their standard anti-tuberculous treatment and duration according to their managing physician
Placebo_comparator: Placebo + standard anti-tuberculous treatment
Placebo twice daily with once daily anti-tuberculous treatment comprising of rifampicin 10 mg/kg, isoniazid 5 mg/kg, ethambutol 15-20 mg/kg, ± pyrazinamide 25 mg/kg and pyridoxine 10-50 mg per day according to managing physicians' discretion. Where needed, the drugs will be adjusted according to renal function. These will be given daily for 8 weeks. Subsequently placebo will be ceased and patients are to continue with their standard anti-tuberculous treatment and duration according to their managing physician.
Sponsors
Collaborators: Luyang Health Clinic, Sabah, Malaysia, Menggatal Health Clinic, Sabah, Malaysia, Tan Tock Seng Hospital, National University of Singapore, Hospital Queen Elizabeth, Malaysia, University Malaysia Sabah
Leads: National University Hospital, Singapore

This content was sourced from clinicaltrials.gov

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