Plasma MTB cfDNA Before Bronchoscopy

NCT07230457 | Not Yet Recruiting

• 1 other identifier: Plasma_MTB_cfDNA_FOB
• Study Type: observational
• Target: 600
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Tuberculosis Diagnosis

Keywords

Pulmonary tuberculosis; Cell-free DNA

Outcome Measures

Primary Outcomes (1)

• 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

  27 months

Secondary Outcomes (1)

• The effect of radiological features on the diagnostic performance (sensitivity and specificity) of the MTB cfDNA assay

  27 months

Study Arms (2)

PTB

Patients with pulmonary tuberculosis

Diagnostic Test: Diagnostic Test: Plasma MTB cfDNA assay

Non-PTB

Patients without pulmonary tuberculosis

Diagnostic Test: Diagnostic Test: Plasma MTB cfDNA assay

Interventions

Diagnostic Test: Plasma MTB cfDNA assay DIAGNOSTIC_TEST

Quantitative measurement of MTB cfDNA level in the plasma

Non-PTB; PTB

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 clinical indications for undergoing bronchoscopy and BAL who meet the inclusion and exclusion criteria will be prospectively enrolled in consecutive sequences

You may qualify if:

• Aged 18 years or above
• Presence of respiratory indication requiring bronchoscopy
• Sputum AFB smear negative or unable to expectorate sputum for investigations

You may not qualify if:

• BALF collected but not sent for MTB PCR
• History of PTB or EPTB
• Concomitant use of at least two anti-TB medications for more than 14 consecutive days in the past 3 months
• Repeated bronchoscopy in the same subject within the study period
• Expected survival of less than 12 months from a different pathology
• Use of unregistered therapeutic agents in the 30 days before the study
• Consent not obtained from the subjects

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (1)

Prince of Wales Hospital

Hong Kong, Hong Kong

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood obtained from patients with PTB and non-PTB will be stored for subsequent genetic sequencing techniques

MeSH Terms

Conditions

Tuberculosis, Pulmonary

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

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: September 30, 2025
• First Posted: November 17, 2025
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): June 30, 2029
• Last Updated: November 17, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)