NCT05473520

Brief 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. 1.To assess improvement in lung function as measured by forced expiratory volume (FEV1) predicted in PTB patients given doxycycline versus placebo.
  2. 2.To investigate whether doxycycline will hasten the resolution of pulmonary cavities measured by CT thorax
  3. 3.To investigate whether doxycycline can suppress inflammatory markers including matrix metalloproteinases
  4. 4.To investigate whether doxycycline can accelerate time to sputum conversion
  5. 5.To evaluate the effect of doxycycline on cardiovascular outcomes such as the incidence of acute coronary syndrome (ACS) and pulmonary hypertension
  6. 6.To investigate whether doxycycline improves TB drug concentrations in sputum and plasma.
  7. 7.To assess the safety profile of doxycycline with concurrent standard anti-tuberculous treatment.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
150

participants targeted

Target at P25-P50 for phase_3

Timeline
45mo left

Started May 2023

Longer than P75 for phase_3

Geographic Reach
2 countries

6 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress44%
May 2023Jan 2030

First Submitted

Initial submission to the registry

June 13, 2022

Completed
1 month until next milestone

First Posted

Study publicly available on registry

July 26, 2022

Completed
10 months until next milestone

Study Start

First participant enrolled

May 24, 2023

Completed
6.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 31, 2030

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 31, 2030

Last Updated

September 9, 2025

Status Verified

August 1, 2025

Enrollment Period

6.7 years

First QC Date

June 13, 2022

Last Update Submit

September 2, 2025

Conditions

TuberculosisAcute Coronary SyndromePulmonary Hypertension (Diagnosis)

Outcome Measures

Primary Outcomes (1)

  • Forced expiratory volume in 1 second (FEV1) at 26 weeks measured by spirometry

    \- 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

    week 0 to 26

Secondary Outcomes (15)

  • Forced expiratory volume in 1 second (FEV1) at 104 weeks measured by spirometry

    104 weeks

  • Forced expiratory volume in 1 second divided by forced vital capacity (FEV1/FVC ratio)

    104 weeks

  • Safety profile

    week 0 to 12

  • Resolution of pulmonary cavities on CT scan

    104 weeks

  • Cumulative lung cavity volume

    week 0 to 104

  • +10 more secondary outcomes

Study Arms (2)

Doxycycline + standard anti-tuberculous treatment

EXPERIMENTAL

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

Drug: Doxycycline

Placebo + standard anti-tuberculous treatment

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

DoxycyclineDRUG

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.

Doxycycline + standard anti-tuberculous treatment
PlaceboDRUG

Placebo + standard anti-tuberculous treatment

Placebo + standard anti-tuberculous treatment

Eligibility Criteria

Age21 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • HIV co-infection
  • Previous pulmonary TB
  • Severe, pre-existing lung disease such as pulmonary fibrosis, bronchiectasis, COPD and lung cancer
  • Pregnant or breast feeding
  • Allergies to tetracyclines
  • Patients on retinoic acid, neuromuscular blocking agents and pimozide which may increase risk of drug toxicity
  • Autoimmune disease and/or on systemic immunosuppressants
  • 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
  • Enrolment in any other clinical trial involving a systemic drug or intervention involving the lung
  • Evidence of severe depression, schizophrenia or mania
  • ALT \> 3 times upper limit of normal
  • Creatinine \> 2 times upper limit of normal
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

Hospital Queen Elizabeth I

Kota Kinabalu, Sabah, Malaysia

NOT YET RECRUITING

Klinik Kesihatan Luyang

Kota Kinabalu, Sabah, Malaysia

ACTIVE NOT RECRUITING

Klinik Kesihatan Menggatal

Kota Kinabalu, Sabah, Malaysia

RECRUITING

Universiti Malaysia Sabah (UMS), Borneo Medical and Health Research Centre

Kota Kinabalu, Sabah, Malaysia

ACTIVE NOT RECRUITING

National University Hospital

Singapore, 119228, Singapore

RECRUITING

TB Control Unit

Singapore, Singapore

RECRUITING

Related Publications (1)

  • Miow QH, Vallejo AF, Wang Y, Hong JM, Bai C, Teo FS, Wang AD, Loh HR, Tan TZ, Ding Y, She HW, Gan SH, Paton NI, Lum J, Tay A, Chee CB, Tambyah PA, Polak ME, Wang YT, Singhal A, Elkington PT, Friedland JS, Ong CW. Doxycycline host-directed therapy in human pulmonary tuberculosis. J Clin Invest. 2021 Aug 2;131(15):e141895. doi: 10.1172/JCI141895.

    PMID: 34128838BACKGROUND

Related Links

MeSH Terms

Conditions

TuberculosisAcute Coronary SyndromeHypertension, PulmonaryDisease

Interventions

Doxycycline

Condition Hierarchy (Ancestors)

Mycobacterium InfectionsActinomycetales InfectionsGram-Positive Bacterial InfectionsBacterial InfectionsBacterial Infections and MycosesInfectionsMyocardial IschemiaHeart DiseasesCardiovascular DiseasesVascular DiseasesLung DiseasesRespiratory Tract DiseasesHypertensionPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

TetracyclinesNaphthacenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic Compounds

Study Officials

  • Catherine Ong, MRCP PhD

    National University Hospital, Singapore

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Srishti CHHABRA, MBBS BSc MRCP

CONTACT

+65 6908 2222srishti.chhabra@mohh.com.sg

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 13, 2022

First Posted

July 26, 2022

Study Start

May 24, 2023

Primary Completion (Estimated)

January 31, 2030

Study Completion (Estimated)

January 31, 2030

Last Updated

September 9, 2025

Record last verified: 2025-08

Data Sharing

IPD Sharing
Will not share

Locations

MY(4)SG(2)