An observational study in Tuberculosis Diagnosis, sponsored by Chinese University of Hong Kong. Not yet recruiting at 1 site in Hong Kong. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-11-17.
Sponsored by Chinese University of Hong Kong · Observational
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.
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.
319 studies on the registry are indexed under Tuberculosis, Pulmonary; 71 are open to participants now.
This study's planned enrollment of 600 is above the median of 300 across 83 observational studies indexed under Tuberculosis, Pulmonary.
Browse Tuberculosis, Pulmonary studies →Chinese University of Hong Kong is the lead sponsor of 1,454 studies on the registry; 474 are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 0 (0%) have results posted.
Counted across the registry records on this site, refreshed daily.
Patients with clinical indications for undergoing bronchoscopy and BAL who meet the inclusion and exclusion criteria will be prospectively enrolled in consecutive sequences
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Patients with pulmonary tuberculosis
Diagnostic Test: Diagnostic Test: Plasma MTB cfDNA assay
Patients without pulmonary tuberculosis
Diagnostic Test: Diagnostic Test: Plasma MTB cfDNA assay
Quantitative measurement of MTB cfDNA level in the plasma
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
Time frame: 27 months
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)
Time frame: 27 months
Plan to share: No
No publications or documents are linked to this record.
Start is estimated for Oct 2026; primary completion for Dec 2028, 26 months later.
Of 44 observational studies under Tuberculosis, Pulmonary, half reached primary completion within 32 months of starting (the median), counting those still running; a quarter within 21 and three quarters within 49. This study's planned 26 months is below that.
How these figures are worked out, and which studies are left out of them.
This study is not yet recruiting, as verified in Nov 2025. You cannot join it, but the record below documents what was studied.
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Chinese University of Hong Kong →