Not Yet RecruitingNot Applicable

Diagnostic Utility of Mycobacterium Tuberculosis Cell-free DNA in Hong Kong

Hong Kong350 participantsStarted 2026-01-01

Plain-language summary

Tuberculosis (TB) is an endemic infectious disease in Hong Kong and a global health threat. Tuberculous pleuritis (TBP) is the most common form of extrapulmonary tuberculosis in China. Its presentation is frequently non-specific and the diagnosis is challenging due to its paucibacillary nature. Various studies have shown that there are limitations for conventional diagnostic modalities, including low sensitivity for pleural fluid microbiological tests (acid-fast bacilli \[AFB\] stain, Mycobacterium tuberculosis \[MTB\] culture and MTB polymerase chain reaction \[PCR\]), lack of specificity for pleural fluid biomarkers (adenosine deaminase) especially in low TB prevalence regions, invasiveness for pleural biopsy (AFB stain, MTB culture and MTB PCR by bedside or pleuroscopy biopsy). The diagnostic journey can be lengthy due to the long turnaround time for microbiological tests and the need for multiple invasive diagnostic procedures. Therefore, the diagnosis of TBP is frequently based on a composite of clinical, radiological and laboratory endpoints to maximise the diagnostic yield and limit the invasiveness. The application of pleural fluid MTB cell-free DNA (cfDNA) as a liquid biopsy to diagnose tuberculous pleuritis has been explored. Previous study groups focused on TB-specific single gene fragments revealed diagnostic sensitivity between 41.4% and 79.5%. Due to the suboptimal sensitivity, the clinical utility based on the previous technique was limited. Our study group has developed a novel MTB cfDNA assay based on different cfDNA processing techniques and interpretation algorithms, with sensitivity and specificity greater than 95% in diagnosing TBP. Since the performance of this novel MTB cfDNA assay was developed based on a limited number of selected cases, its clinical utility should be examined in a non-selective cohort of new-onset unilateral pleural effusion. Successful validation of MTB cfDNA in pleural fluid, as a liquid biopsy obtained through thoracentesis, can obviate the need to perform a pleural biopsy.

Who can participate

Age range18 Years

SexALL

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Inclusion Criteria: * Patients hospitalised for new-onset unilateral pleural effusion. * Thoracentesis will be performed for pleural fluid analysis. * Age equals or is above 18 years old * Written informed consent is obtained Exclusion Criteria: * History of intrapleural therapy (including talc and fibrinolytic), surgical decortication or surgical pleurodesis in the ipsilateral pleural space in the past 3 months * Concomitant use of at least two anti-TB medications (including isoniazid, rifampicin, pyrazinamide, ethambutol, amikacin, streptomycin, levofloxacin, moxifloxacin, linezolid) for more than consecutive 7 days in the past 3 months * Failed to obtain informed consent due to patient's refusal or cognitive impairment. * History of TBP in the ipsilateral pleural space * Expected survival of less than three months from a different pathology (e.g. advanced metastatic malignancy) as that further pleural investigations may not be able to carry out if negative initial workup. * Use of agents under research or not registered in the 30 days prior to the study

What they're measuring

Diagnostic performance of MTB cfDNA assay

Timeframe: 12 months

Trial details

NCT IDNCT06646237

SponsorChinese University of Hong Kong

Sponsor typeOTHER

Study typeOBSERVATIONAL

Primary completion2027-12-31

Contact for this trial

Ka Pang Chan, MBChB

35052211 chankapang@cuhk.edu.hk