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

• Status: Not yet recruiting
• Trial end date: 2024-12-27
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: National University Hospital, Singapore
• Collaborators: Hospital Queen Elizabeth, Malaysia; National University, Singapore; Tan Tock Seng Hospital
• Treatments: Doxycycline

Criteria

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 ≤ 7 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