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

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.

Conditions

• Tuberculosis
• Acute Coronary Syndrome
• Pulmonary Hypertension (Diagnosis)

Interventions

DRUG

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.

DRUG

Placebo

Placebo + standard anti-tuberculous treatment

Sponsors & Collaborators

• Tan Tock Seng Hospital

  collaborator OTHER

• Hospital Queen Elizabeth, Malaysia

  collaborator OTHER_GOV

• National University of Singapore

  collaborator OTHER

• University Malaysia Sabah

  collaborator UNKNOWN

• Menggatal Health Clinic, Sabah, Malaysia

  collaborator UNKNOWN

• Luyang Health Clinic, Sabah, Malaysia

  collaborator UNKNOWN

• National University Hospital, Singapore

  lead OTHER

Principal Investigators

• Catherine Ong, MRCP PhD · National University Hospital, Singapore

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-05-24

Primary Completion

2030-01-31

Completion

2030-01-31

Countries

• Malaysia
• Singapore

Study Locations