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

NCT05473520 · tracked via the Priya Life Science Singapore tracker

Sponsor

National University Hospital, Singapore

Phase

Phase 3

Started

2023-05-24

Last updated

2026-06-09

Condition(s) studied

TuberculosisAcute Coronary SyndromePulmonary Hypertension (Diagnosis)

Investigational drug(s) / intervention(s)

Doxycycline →Placebo

Doxycycline: A dose of 100 mg twice daily of doxycycline based on the recommended dose for adults which is commonly used for bacterial infections such as rickettsial infection, lyme disease and pelvic inflammatory disease.

Placebo: Placebo + standard anti-tuberculous treatment

Study 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

Sex

ALL

Min age

21 Years

Max age

—

Healthy volunteers

The recruitment target would be 150 patients, with 75 in each arm Inclusion criteria: Patients should meet all criteria: 1. Aged 21 years and above 2. Patients receiving ≤ 14 days of TB treatment or about to start standard combination TB treatment 3. Confirmed pulmonary TB with positive acid-fast bacilli smear and/or positive nucleic acid amplification test (NAAT) and/or TB culture results 4. CXR demonstrating pulmonary involvement with cavity or cavities 5. Able to provide informed consent Exclusion criteria: 1. HIV co-infection 2. Previous pulmonary TB 3. Severe, pre-existing lung disease such as pulmonary fibrosis, bronchiectasis, COPD and lung cancer 4. Pregnant or breast feeding 5. Allergies to tetracyclines 6. Patients on retinoic acid, neuromuscular blocking agents and pimozide which may increase risk of drug toxicity 7. Autoimmune disease and/or on systemic immunosuppressants 8. Use of any investigational or non-registered drug, vaccine or medical device other than the study drug within 182 days preceding dosing of study drug, or planned use during the study period 9. Enrolment in any other clinical trial involving a systemic drug or intervention involving the lung 10. Evidence of severe depression, schizophrenia or mania 11. ALT \> 3 times upper limit of normal 12. Creatinine \> 2 times upper limit of normal 13. Principal investigator assessment of lack of willingness to participate and comply with all requirements including follow-up of the protocol, or identification of any factor felt to significantly increase the participant's risk of suffering an adverse outcome

Primary outcome measure(s)

Forced expiratory volume in 1 second (FEV1) at 26 weeks measured by spirometry — week 0 to 26
\- FEV1 at 26 weeks, expressed as a percentage predicted for age, sex, height and race will be measured by spirometry and will be compared between the doxycycline and placebo group

Trial sites (6)

Facility	City	Region	Status
Hospital Queen Elizabeth I	Kota Kinabalu	Sabah	Not Yet Recruiting
Klinik Kesihatan Luyang	Kota Kinabalu	Sabah	Active Not Recruiting
Klinik Kesihatan Menggatal	Kota Kinabalu	Sabah	Recruiting
Universiti Malaysia Sabah (UMS), Borneo Medical and Health Research Centre	Kota Kinabalu	Sabah	Active Not Recruiting
National University Hospital	Singapore	Singapore	Recruiting
TB Control Unit	Singapore	Singapore	Recruiting

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Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT05473520 on ClinicalTrials.gov ↗ ← All trials in Singapore