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

NCT06646237 | Not Yet Recruiting

• 1 other identifier: MYDNITE-3
• Study Type: observational
• Target: 350
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Tuberculosis, Pleural; Pleural Biopsy

Keywords

Tuberculous pleuritis; cell-free DNA; Tuberculosis; pleural biopsy

Outcome Measures

Primary Outcomes (1)

• Diagnostic performance of MTB cfDNA assay

  The diagnostic performance (sensitivity and specificity) of MTB cfDNA assay with a pre-defined cutoff level in discriminating TBP and non-TBP in a prospective non-selective cohort of new-onset unilateral pleural effusions

  12 months

Secondary Outcomes (3)

• Factor affecting the test performance of MTB cfDNA assay

  12 months

• Compare the diagnostic performance

  12 months

• Estimate the proportion of pleural biopsy can be avoided

  12 months

Study Arms (2)

TBP

Patients with definite or probable tuberculous pleuritis

Non-TBP

Patients without tuberculous pleuritis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with definite or probably TBP will be recruited as positive control. Patients without TBP will be recruited as negative control.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (1)

Chinese University of Hong Kong

Hong Kong, Hong Kong, Hong Kong

Location

Biospecimen

Retention: SAMPLES WITH DNA

Pleural fluid and blood obtained from patients with TBP and non-TBP will be stored for subsequent genetic sequencing techniques.

MeSH Terms

Conditions

Tuberculosis, Pleural; Tuberculosis

Condition Hierarchy (Ancestors)

Tuberculosis, Extrapulmonary; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Pleural Diseases; Respiratory Tract Diseases

Study Officials

• David SC Hui, MD

  Chinese University of Hong Kong

  STUDY DIRECTOR

Central Study Contacts

Ka Pang Chan, MBChB

CONTACT

35052211; chankapang@cuhk.edu.hk

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Target Duration: 12 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: October 11, 2024
• First Posted: October 17, 2024
• Study Start: January 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: December 16, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)