A Phase 3 interventional study of Doxycycline and Placebo in Tuberculosis, Acute Coronary Syndrome and Pulmonary Hypertension (Diagnosis), sponsored by National University Hospital, Singapore. Recruiting at 6 sites in 2 countries. Open to participants aged 21 Years and older. Per ClinicalTrials.gov, last updated 2026-06-09.
Sponsored by National University Hospital, Singapore · Phase 3, Interventional, and Treatment
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
In this Phase 3 double-blind randomised-controlled trial, doxycycline or placebo shall be given to 75 PTB patients in each arm for two months with a further follow-up of twenty-two months. Study sites are National University Hospital and TB Control Unit in Singapore and Luyang Health Clinic, Menggatal Health Clinic, and Inanam Health Clinic in Sabah, Malaysia. Lung function tests, non-contrast CT thorax, electrocardiograms and transthoracic echocardiograms will be performed at various time intervals. Induced sputum and plasma samples from all PTB patients shall be analysed for matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs) and monitored for sputum mycobacteria culture conversion. Whole blood will be analysed by transcriptomics for bulk RNAseq while a subset of patients' blood will be analysed using single-cell RNAsequencing. Blood tests will also be taken for Troponin-I and N-terminal pro-B-type natriuretic peptide. Accomplishing these specific aims will determine if doxycycline decreases PIAT by improving lung function, reducing pulmonary cavities and accelerating sputum culture conversion. We will also be able to assess the effect of doxycycline on development of pulmonary hypertension and acute coronary syndrome. The results will positively impact clinical practice and international guidelines including the World Health Organisation that we collaborate with, for the treatment of pulmonary TB.
1,170 studies on the registry are indexed under Tuberculosis; 175 are open to participants now.
This study's planned enrollment of 150 is close to the median of 150 across 820 interventional studies indexed under Tuberculosis.
Browse Tuberculosis studies →National University Hospital, Singapore is the lead sponsor of 454 studies on the registry; 99 are open to participants now.
Counted across the registry records on this site, refreshed daily.
The recruitment target would be 150 patients, with 75 in each arm
Inclusion criteria: Patients should meet all criteria:
Exclusion criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
COPD
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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 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
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 + standard anti-tuberculous treatment
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
Time frame: week 0 to 26
Forced expiratory volume in 1 second (FEV1) at 104 weeks measured by spirometry
Forced expiratory volume, 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 will be measured at D0, week 8, week 26, week 52, week 78 and week 104.
Time frame: 104 weeks
Forced expiratory volume in 1 second divided by forced vital capacity (FEV1/FVC ratio)
Forced expiratory volume in 1 second divided by forced vital capacity (FEV1/FVC ratio) measured by spirometry
Time frame: 104 weeks
Safety profile
Incidence of Grade 3 or 4 adverse events and serious adverse events
Time frame: week 0 to 12
Resolution of pulmonary cavities on CT scan
Proportion of patients in each study group with resolution of pulmonary cavities on CT scan done at 26, 52, 78, 104 weeks
Time frame: 104 weeks
Cumulative lung cavity volume
Change in cumulative lung cavity volume (in cm3) measured on CT scan
Time frame: week 0 to 104
St George's Respiratory Questionnaire Score
Change in Quality-of-life score by the St George's Respiratory Questionnaire will be measured. Scores range from 0 to 100, with higher scores indicating more limitations.
Time frame: week 0 to 104
Sputum TB culture
Time taken in days for positivity of sputum TB culture using MGIT will be assessed
Time frame: up to 8 weeks
Sputum culture conversion
Time taken for sputum culture conversion (time taken for sputum cultures to turn negative) by liquid cultures will be investigated
Time frame: up to 8 weeks
Sputum matrix metalloproteinase (MMP) concentration
Change of sputum matrix metalloproteinase (MMP) concentration will be measured by Luminex array
Time frame: up to 8 weeks
Sputum functional assays
Change in sputum functional assays by sputum collagenase and elastase assay will be assessed.
Time frame: up to 8 weeks
Host transcriptome
Change of host transcriptome will be measured via bulk RNA sequencing. In addition, in the subset of patients recruited from Singapore, single-cell RNA sequencing (scRNAseq) will be performed for neutrophils and peripheral blood mononuclear cells on 10 patients each from the doxycycline and placebo arm, analysing 10,000 cells per sample.
Time frame: week 0 to 104
Host plasma matrix metalloproteinase (MMP) concentration
Change in host plasma matrix metalloproteinase (MMP) concentration will be measured by Luminex array
Time frame: week 0 to 104
Pharmacokinetics and pharmacodynamics of drug concentrations
Sputum and plasma drug concentration of rifampicin, isoniazid, ethambutol, pyrazinamide (if prescribed) and doxycycline for a subset PK/PD study
Time frame: week 2
Cardiac function and pulmonary hypertension
Cardiac function and pulmonary artery systolic pressure will be measured using 2D Echocardiogram and electrocardiogram at D0, week 26, week 52, week 78 and week 104. The time-to-development of pulmonary hypertension over 2 years follow-up will be calculated.
Time frame: week 0 to 104
Measurement of Troponin I and NT-proBNP
HsTnI and NT-proBNP will be measured sequentially at Day 0, Week 2, 8, 26, 52, 78 and 104 to screen for cardiotoxicity, which will then be ascertained by review of source documents.
Time frame: week 0 to 104
Not enrolling at this site.
Not enrolling at this site.
Plan to share: No
Started May 2023 (actual). Primary completion is estimated for Jan 2030, 80 months after the start.
Of 33 non-industry phase 3 interventional studies under Tuberculosis, half reached primary completion within 54 months of starting (the median), counting those still running; a quarter within 38 and three quarters within 67. This study's planned 80 months is above that.
Counting every sponsor, half of 40 studies reached it within 55 months; a quarter within 38 and three quarters within 76.
How these figures are worked out, and which studies are left out of them.
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Studies of the drug tested here: Doxycycline
National University Hospital, Singapore →