Tuberculosis DiagnosisNCT07230457
Plasma MTB cfDNA Before Bronchoscopy
An observational study of Tuberculosis Diagnosis, run by Chinese University of Hong Kong at 1 site in Hong Kong.
Trial summary
Tuberculosis (TB) remains a major global health challenge, affecting over 10 million people annually. Hong Kong carries an intermediate TB burden, with ~3,200 new cases reported yearly. Pulmonary TB (PTB), the most common form, presents diagnostic difficulties. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tuberculosis Diagnosis
- What is being tested?
- Diagnostic Test: Plasma MTB cfDNA assay
- How many people
- 600 participants
- Where
- 1 siteHong Kong
- Study dates
- 1 Oct 2026to 30 Jun 2029
- How long will I take part?
- 12 Months
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with clinical indications for undergoing bronchoscopy and BAL who meet the inclusion and exclusion criteria will be prospectively enrolled in consecutive sequences
Who may be able to join
- Aged 18 years or above
- Presence of respiratory indication requiring bronchoscopy
- Sputum AFB smear negative or unable to expectorate sputum for investigations
Who cannot join
- BALF collected but not sent for MTB PCR
- History of PTB or EPTB
- Concomitant use of at least two anti-TB medications for more than 14 consecutive days in the past 3 months
- Repeated bronchoscopy in the same subject within the study period
- Expected survival of less than 12 months from a different pathology
- Use of unregistered therapeutic agents in the 30 days before the study
- Consent not obtained from the subjects
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Hong Kong1 site
Prince of Wales Hospital
Hong Kong
Ka Pang Chan, MBChB, 35052211, chankapang@cuhk.edu.hk
Karen Yiu, 35053532, ysyiu@cuhk.edu.hk
About this study
Official title: Prospective Evaluation of Plasma Mycobacterium Tuberculosis Cell-free DNA Sequencing as a Non-Invasive Alternative to Bronchoscopy for Diagnosing Pulmonary Tuberculosis
Tuberculosis (TB) remains a major global health challenge, affecting over 10 million people annually. Hong Kong carries an intermediate TB burden, with ~3,200 new cases reported yearly. Pulmonary TB (PTB), the most common form, presents diagnostic difficulties. Traditional methods like sputum smear and culture often fail in patients unable to produce adequate samples, necessitating bronchoscopy to collect bronchoalveolar lavage (BAL) for mycobacterial testing.
These limitations pose risks for patients and strain healthcare systems. Bronchoscopy is invasive, resource-intensive, and may delay treatment-especially for elderly patients with comorbidities. Blood-based inflammatory markers lack diagnostic specificity. A rapid, non-invasive alternative is urgently needed.
Read more
The investigators developed a plasma-based assay that detects Mycobacterium tuberculosis cell-free DNA (MTB cfDNA) in blood. This liquid biopsy leverages metagenomic sequencing and computational analysis to identify TB-specific genetic material while minimizing contamination. Preliminary data show excellent diagnostic performance, with area under the receiver operating characteristic curve values >0.94 for TB pleurisy.
The investigators propose a prospective clinical validation study comparing plasma MTB cfDNA testing to bronchoscopy with BAL culture and molecular testing. The primary aim is to demonstrate non-inferiority of plasma cfDNA within a 10% sensitivity margin. Secondary aims include assessing how clinical and radiological features affect test performance and evaluating the assay's ability to detect drug resistance mutations for personalized therapy.
Validation could transform TB diagnosis by offering a rapid, safe, and accurate blood test. Patients could avoid invasive procedures, receive faster diagnoses, and begin treatment sooner. Detecting resistance mutations directly from plasma would enable timely, targeted therapy-critical for addressing multidrug-resistant TB. This represents a paradigm shift toward precision medicine in TB care.
Tailored to Hong Kong's epidemiological context, this study addresses a key diagnostic gap. The approach has global relevance, with potential to improve clinical outcomes, reduce costs, and accelerate progress toward WHO's TB elimination goals.
Read the detailed description
Tuberculosis (TB) remains a global health challenge, particularly in East Asia. According to the Global TB Report by the World Health Organisation (WHO) in 2024, over 10 million people contracted TB in 2023, with 1.25 million deaths attributed to the disease. India, Indonesia and China bear the highest burden, while Hong Kong maintains an intermediate incidence, averaging 3,200 new cases annually.
Pulmonary tuberculosis (PTB) is the most common form of active TB disease. Diagnosis typically relies on detecting Mycobacterium tuberculosis (MTB) in the sputum via smear microscopy, culture, or polymerase chain reaction (PCR). However, sputum smear has limited sensitivity, culture requires 6-8 weeks, and sputum production is often difficult in certain patients. PTB may present with heterogeneous radiological features, sometimes mimicking malignancy, prompting bronchoscopy with bronchoalveolar lavage (BAL) in smear-negative patients. BAL fluid (BALF) is then tested via MTB culture, PCR, and cytology. Bronchoscopy, while informative, is invasive and poses risks for elderly patients or with cardiopulmonary comorbidities. Temporary interruption of oral anticoagulants, now widely prescribed, can lead to cardioembolic complications, contributing to up to 2.6% of stroke events. Delays in scheduling bronchoscopy and awaiting BALF MTB culture results further hinder timely diagnosis. Blood inflammatory markers are non-specific. These limitations underscore the need for a non-invasive, rapid, and accurate diagnostic tool for PTB.
Advances in sequencing technology offer new diagnostic possibilities. When bacteria die, their DNA fragments enter the bloodstream as cell-free (cfDNA). Detecting microbial cfDNA in plasma, combined with bioinformatics, provides a minimally invasive method to identify pathogens directly, outperforming blood culture or surrogate markers. Plasma MTB cfDNA is an emerging diagnostic tool. The IntelliGenome CRISPR-TB Blood Test can detect MTB cfDNA and its landmark study focused on paediatric and HIV-positive populations. However, its clinical application remains limited, with no validation in intermediate-burden regions like Hong Kong, where HIV prevalence is low.
The investigator has developed a novel targeted MTB cfDNA sequencing assay. The assay uses whole-genome-based sequencing to enrich the MTB cfDNA, followed by bioinformatic filtering to remove human DNA, distinguishing MTB from non-tuberculous Mycobacterium (NTM), and exclude microbial contaminants. A prospective study would be required to confirm diagnostic accuracy and clinical utility of this new sequencing assay. The investigators hypothesise that plasma targeted MTB cfDNA sequencing is non-inferior to BALF MTB culture and PCR in diagnostic smear-negative patients undergoing bronchoscopy.
- Conditions
- Tuberculosis Diagnosis
- Being tested
- Diagnostic Test: Plasma MTB cfDNA assay
- Keywords
- Pulmonary tuberculosis, Cell-free DNA
- Medical subject headings
- Tuberculosis, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Diagnostic Test: Plasma MTB cfDNA assayDiagnostic test
Quantitative measurement of MTB cfDNA level in the plasma
| Study group | Role | What they receive |
|---|---|---|
| PTB | Patients with pulmonary tuberculosis Receives: Diagnostic Test: Diagnostic Test: Plasma MTB cfDNA assay | |
| Non-PTB | Patients without pulmonary tuberculosis Receives: Diagnostic Test: Diagnostic Test: Plasma MTB cfDNA assay |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under ROC curve of MTB cfDNA assay
The area under ROC curve of MTB cfDNA assay in discriminating PTB and non-PTB in a prospective non-selective cohort of bronchoscopy procedures
Measured: 27 months
Secondary outcomes (1)
The effect of radiological features on the diagnostic performance (sensitivity and specificity) of the MTB cfDNA assay
To compare the diagnostic performance (sensitivity and specificity) of the MTB cfDNA assay in patients with different radiological features (cavitary vs non-cavitary)
Measured: 27 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2025
- Study start1 Oct 2026 (estimated)
- Primary completion31 Dec 2028 (estimated)
- Study completion30 Jun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tuberculosis DiagnosisStudies of the same condition, open and under way.
- More trials run by Chinese University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 600 participants (estimated)
- Target duration
- 12 Months
Sponsor and investigators
- Lead sponsor
- Chinese University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ka Pang Chan, Chinese University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07230457
- Sponsor's protocol ID
- Plasma_MTB_cfDNA_FOB
- Status last verified
- Nov 2025
- First submitted
- 30 Sep 2025
- Last updated
- 17 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Evaluation of Plasma Mycobacterium Tuberculosis Cell-free DNA Sequencing as a Non-Invasive Alternative to Bronchoscopy for Diagnosing Pulmonary Tuberculosis
- ClinicalTrials.gov ID
- NCT07230457
- Acronym / sponsor ID
- Plasma_MTB_cfDNA_FOB
- Conditions
- Tuberculosis Diagnosis
- Keywords
- Pulmonary tuberculosis, Cell-free DNA
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 600 participants (estimated)
- Lead sponsor
- Chinese University of Hong KongUniversity, hospital or other
- Study start
- 1 Oct 2026 (estimated)
- Primary completion
- 31 Dec 2028 (estimated)
- Study completion
- 30 Jun 2029 (estimated)
- First posted
- 17 Nov 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Tuberculosis (TB) remains a major global health challenge, affecting over 10 million people annually. Hong Kong carries an intermediate TB burden, with ~3,200 new cases reported yearly. Pulmonary TB (PTB), the most common form, presents diagnostic difficulties. Traditional methods like sputum smear and culture often fail in patients unable to produce adequate samples, necessitating bronchoscopy to collect bronchoalveolar lavage (BAL) for mycobacterial testing.
These limitations pose risks for patients and strain healthcare systems. Bronchoscopy is invasive, resource-intensive, and may delay treatment-especially for elderly patients with comorbidities. Blood-based inflammatory markers lack diagnostic specificity. A rapid, non-invasive alternative is urgently needed.
The investigators developed a plasma-based assay that detects Mycobacterium tuberculosis cell-free DNA (MTB cfDNA) in blood. This liquid biopsy leverages metagenomic sequencing and computational analysis to identify TB-specific genetic material while minimizing contamination. Preliminary data show excellent diagnostic performance, with area under the receiver operating characteristic curve values >0.94 for TB pleurisy.
The investigators propose a prospective clinical validation study comparing plasma MTB cfDNA testing to bronchoscopy with BAL culture and molecular testing. The primary aim is to demonstrate non-inferiority of plasma cfDNA within a 10% sensitivity margin. Secondary aims include assessing how clinical and radiological features affect test performance and evaluating the assay's ability to detect drug resistance mutations for personalized therapy.
Validation could transform TB diagnosis by offering a rapid, safe, and accurate blood test. Patients could avoid invasive procedures, receive faster diagnoses, and begin treatment sooner. Detecting resistance mutations directly from plasma would enable timely, targeted therapy-critical for addressing multidrug-resistant TB. This represents a paradigm shift toward precision medicine in TB care.
Tailored to Hong Kong's epidemiological context, this study addresses a key diagnostic gap. The approach has global relevance, with potential to improve clinical outcomes, reduce costs, and accelerate progress toward WHO's TB elimination goals.
Detailed description
Tuberculosis (TB) remains a global health challenge, particularly in East Asia. According to the Global TB Report by the World Health Organisation (WHO) in 2024, over 10 million people contracted TB in 2023, with 1.25 million deaths attributed to the disease. India, Indonesia and China bear the highest burden, while Hong Kong maintains an intermediate incidence, averaging 3,200 new cases annually.
Pulmonary tuberculosis (PTB) is the most common form of active TB disease. Diagnosis typically relies on detecting Mycobacterium tuberculosis (MTB) in the sputum via smear microscopy, culture, or polymerase chain reaction (PCR). However, sputum smear has limited sensitivity, culture requires 6-8 weeks, and sputum production is often difficult in certain patients. PTB may present with heterogeneous radiological features, sometimes mimicking malignancy, prompting bronchoscopy with bronchoalveolar lavage (BAL) in smear-negative patients. BAL fluid (BALF) is then tested via MTB culture, PCR, and cytology. Bronchoscopy, while informative, is invasive and poses risks for elderly patients or with cardiopulmonary comorbidities. Temporary interruption of oral anticoagulants, now widely prescribed, can lead to cardioembolic complications, contributing to up to 2.6% of stroke events. Delays in scheduling bronchoscopy and awaiting BALF MTB culture results further hinder timely diagnosis. Blood inflammatory markers are non-specific. These limitations underscore the need for a non-invasive, rapid, and accurate diagnostic tool for PTB.
Advances in sequencing technology offer new diagnostic possibilities. When bacteria die, their DNA fragments enter the bloodstream as cell-free (cfDNA). Detecting microbial cfDNA in plasma, combined with bioinformatics, provides a minimally invasive method to identify pathogens directly, outperforming blood culture or surrogate markers. Plasma MTB cfDNA is an emerging diagnostic tool. The IntelliGenome CRISPR-TB Blood Test can detect MTB cfDNA and its landmark study focused on paediatric and HIV-positive populations. However, its clinical application remains limited, with no validation in intermediate-burden regions like Hong Kong, where HIV prevalence is low.
The investigator has developed a novel targeted MTB cfDNA sequencing assay. The assay uses whole-genome-based sequencing to enrich the MTB cfDNA, followed by bioinformatic filtering to remove human DNA, distinguishing MTB from non-tuberculous Mycobacterium (NTM), and exclude microbial contaminants. A prospective study would be required to confirm diagnostic accuracy and clinical utility of this new sequencing assay. The investigators hypothesise that plasma targeted MTB cfDNA sequencing is non-inferior to BALF MTB culture and PCR in diagnostic smear-negative patients undergoing bronchoscopy.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Target follow-up
- 12 Months
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PTB | – | Diagnostic Test: Diagnostic Test: Plasma MTB cfDNA assayPatients with pulmonary tuberculosis |
| Non-PTB | – | Diagnostic Test: Diagnostic Test: Plasma MTB cfDNA assayPatients without pulmonary tuberculosis |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with clinical indications for undergoing bronchoscopy and BAL who meet the inclusion and exclusion criteria will be prospectively enrolled in consecutive sequences
Key inclusion criteria (3 listed)
- Aged 18 years or above
- Presence of respiratory indication requiring bronchoscopy
- Sputum AFB smear negative or unable to expectorate sputum for investigations
Key exclusion criteria (7 listed)
- BALF collected but not sent for MTB PCR
- History of PTB or EPTB
- Concomitant use of at least two anti-TB medications for more than 14 consecutive days in the past 3 months
- Repeated bronchoscopy in the same subject within the study period
- Expected survival of less than 12 months from a different pathology
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Diagnostic Test: Plasma MTB cfDNA assayQuantitative measurement of MTB cfDNA level in the plasma | Diagnostic test | Non-PTB, PTB |
Primary outcome
Area under ROC curve of MTB cfDNA assay
Time frame: 27 months
The area under ROC curve of MTB cfDNA assay in discriminating PTB and non-PTB in a prospective non-selective cohort of bronchoscopy procedures
1 secondary outcome
The effect of radiological features on the diagnostic performance (sensitivity and specificity) of the MTB cfDNA assay
Time frame: 27 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Nov 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Tuberculosis Diagnosis, run by Chinese University of Hong Kong at 1 site in Hong Kong.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 17 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ka Pang Chan, MBChB (35052211, chankapang@cuhk.edu.hk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area under ROC curve of MTB cfDNA assay (time frame: 27 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Nov 2025; AzTrials last refreshed its copy on 27 Oct 2026.