MTB cfDNA Levels in TBP

NCT05397730 | Completed

• 1 other identifier: TBP_cfDNA_levels
• Study Type: observational
• Target: 329
• Locations: 1 country
• Sites: 1

Brief Summary

Tuberculous pleuritis (TBP) is the most common manifestation of extrapulmonary TB. Its diagnosis is challenging due to the low sensitivity of mycobacterial culture from the pleural fluid and the need for invasive pleural biopsy. Preliminary data has shown the superior sensitivity of Mycobacterium tuberculosis cell-free DNA (MTB cfDNA) to conventional culture and MTB polymerase chain reaction (PCR), but the cutoff level of MTB cfDNA was not determined. This study involves a prospective collection of pleural fluid due to TBP and non-TBP aetiologies, with subsequent testing by MTB culture, MTB cfDNA and MTB PCR. The levels of MTB cfDNA in the pleural fluid will be correlated with different types of diagnosis, and its diagnostic accuracy will be compared with conventional culture and MTB PCR. A confirmatory study result of MTB cfDNA can shorten the time to diagnosis, reduce the need for pleural biopsy and prevent the delay of definitive treatment.

Conditions

Tuberculosis, Pleural

Keywords

Tuberculosis, Tuberculous pleuritis, cell-free DNA

Outcome Measures

Primary Outcomes (1)

• The MTB cfDNA level in TBP and non-TB pleural effusions

  The median MTB cfDNA level in TBP and non-TB pleural effusions

  24 months

Secondary Outcomes (2)

• The diagnostic performance of MTB cfDNA and Xpert Ultra in diagnosing MTB culture-positive and MTB culture-negative TBP

  24 months

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

  24 months

Study Arms (2)

TBP

Patients with definite or probable tuberculous pleuritis

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

Non-TBP

Patients without tuberculous pleuritis

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

Interventions

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

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

Also known as: Mycobacterium tuberculosis PCR

Non-TBP; TBP

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:

• Patients hospitalized for unilateral pleural effusion.
• Pleural tapping will be performed for pleural fluid analysis.
• Aged 18 years old or above

You may not qualify if:

• History of tuberculous pleuritis (TBP) and bacterial pleural infection, in either ipsilateral or contralateral pleural space.
• History of intrapleural therapy (including talc and fibrinolytic) in the ipsilateral pleural space.
• History of surgical decortication or pleurodesis in the ipsilateral pleural space
• Use of anti-TB medications (including isoniazid, rifampicin, pyrazinamide, ethambutol, amikacin, streptomycin, levofloxacin, moxifloxacin, linezolid) for more than consecutive 14 days in the past 3 months.
• Failed to obtain informed consent due to patient's refusal or cognitive impairment

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (1)

Prince of Wales Hospital

Hong Kong, Hong Kong, Hong Kong

Location

Related Publications (1)

• Lam WKJ, Chan KKP, Wang G, Lai CKC, Kang G, Chan C, Leung ACY, Wong NHL, Tso CSN, Chow KM, Ramakrishnan S, Wong KT, Lau CHY, Ng JKC, Lo RLP, Yip WH, Ngai JCL, To KW, Tse IOL, Cheng SH, Shang H, Chan KW, Lai A, Chan CML, Lee VCT, Malki Y, Choy LYL, Ma ML, Zhou Q, Yu SCY, Jiang P, Ko FWS, Chan KCA, Hui DSC, Lee YCG, Lo YMD. Sequencing of Pleural Fluid and Plasma for Tuberculous Pleuritis. NEJM Evid. 2026 Apr;5(4):EVIDoa2500237. doi: 10.1056/EVIDoa2500237. Epub 2026 Mar 24.

  PMID: 41874256 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Pleural fluid and blood obtained from patients with TBP and non-TBP will be stored for subsequent analysis using 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 Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor (Clinical Lecturer)

Study Record Dates

• First Submitted: May 23, 2022
• First Posted: May 31, 2022
• Study Start: September 1, 2022
• Primary Completion: March 31, 2024
• Study Completion: December 31, 2025
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)