Diagnostic Utility of Mycobacterium Tuberculosis Cell-free DNA

NCT06439810 | Recruiting

• 1 other identifier: PF_MTB cfDNA
• Study Type: observational
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

Tuberculosis (TB) is one of the major global health threats and is the second leading infectious cause of death after COVID-19 in 2022. Extrapulmonary TB (EPTB), amongst which tuberculous pleuritis (TBP) is one of the most common subtypes, poses additional obstacles to global TB control due to its difficulty in diagnosis. The diagnosis of TBP is challenging. The ideal way of confirming TBP is by direct detection of TB bacteria or its specific component in the pleural space. However, the performance of available diagnostic tests is far from satisfactory, and no single test can achieve multiple diagnostic goals simultaneously, including high detection sensitivity, high specificity to exclude other diseases, low invasiveness and detection of drug resistance. The inability to diagnose TBP early leads to unnecessary invasive pleural procedures and delayed curative treatment. There is a pressing need for a better diagnostic test to diagnose TBP confidently. When TB bacteria die or break down, the DNA materials shed into the pleural space, forming Mycobacterium tuberculosis cell-free DNA (MTB cfDNA), which may aid in diagnosing TBP. However, only limited literature explored this aspect, and the sensitivity rates reported were still suboptimal due to the scarcity of DNA materials in the pleural fluid. Based on a small patient cohort, our group has recently developed a new laboratory assay measuring MTB cfDNA to overcome this problem, with a superior diagnostic performance to conventional tests. This assay can potentially capture the genes harbouring drug resistance towards anti-TB medications. There are three aims in this research proposal. First, the diagnostic accuracy of the new MTB cfDNA assay in diagnosing TBP will be determined using a large cohort containing pleural fluid samples of various causes from countries with different TB burdens. Second, the clinical and laboratory factors determining the pleural fluid MTB cfDNA level will be identified. Third, the ability of the assay to capture different anti-TB drug-resistance genes will be explored. This new diagnostic method will significantly enhance the pickup rate of TBP, benefit patients with less invasive procedures, shorter hospital stays and timely treatment.

Conditions

Tuberculosis, Pleural

Keywords

Tuberculosis; Tuberculous pleuritis; cell-free DNA

Outcome Measures

Primary Outcomes (1)

• diagnostic accuracy of the new MTB cfDNA assay

  to evaluate the diagnostic accuracy of the new MTB cfDNA assay in a randomly selected cohort of pleural effusions containing TBP and non-TBP aetiologies.

  24 months

Secondary Outcomes (3)

• Diagnostic performance of the new MTB cfDNA assay

  24 months

• Clinical factors that may affect the levels of MTB cfDNA in TBP

  24 months

• Diagnostic performance of the new MTB cfDNA assay (drug resistant TB)

  24 months

Study Arms (2)

Tuberculous pleuritis

Patients with definite or probable tuberculous pleuritis

Diagnostic Test: Mycobacterium tuberculosis (MTB) cell-free DNA (cfDNA)

Non-tuberculous pleuritis

Patients without tuberculous pleuritis

Diagnostic Test: Mycobacterium tuberculosis (MTB) cell-free DNA (cfDNA)

Interventions

Mycobacterium tuberculosis (MTB) cell-free DNA (cfDNA) DIAGNOSTIC_TEST

Comparing the diagnostic accuracy between MTB cfDNA and PCR on diagnosing tuberculous pleuritis

Also known as: Mycobacterium tuberculosis PCR

Non-tuberculous pleuritis; Tuberculous pleuritis

Eligibility Criteria

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

• New-onset pleural effusion planning for thoracentesis
• Age 18 years or above
• Able to give informed consent

You may not qualify if:

• History of TBP or intrapleural therapy (including talc and fibrinolytic) in the ipsilateral pleural space. Patients with a history of TB outside the pleural space completed anti-TB treatment can be included
• History of surgical intervention (including decortication, pleurodesis, lung resection) in the ipsilateral pleural space
• 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
• Consent not obtained from the participants

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (1)

Chinese University of Hong Kong

Shatin, Hong Kong, 000, Hong Kong

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Pleural fluid for cell-free DNA extraction

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

• Ka Pang Chan, MBChB

  Prince of Wales Hospital

  PRINCIPAL INVESTIGATOR

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
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor (Assistant Professor)

Study Record Dates

• First Submitted: May 28, 2024
• First Posted: June 3, 2024
• Study Start: April 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)