Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05935696 |
| Other study ID # |
TUS-TBE v4.0 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
April 1, 2023 |
| Est. completion date |
March 31, 2024 |
Study information
| Verified date |
June 2023 |
| Source |
Sarawak General Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Primary Endpoint
- To assess the prevalence and diagnostic performance of pre-determined echographic
features in predicting the diagnosis of TBE from MPE.
- To determine the clinical, pleural fluid and echographic parameters that were different
among TBE and MPE and to establish a clinical prediction model for TBE.
Secondary Endpoint
- To assess the correlation between pleural fluid parameters with ultrasound and medical
thoracoscopic finding.
- To assess the optimal Pf ADA cut-off value to differentiate TBE from MPE in our region.
Description:
Tuberculous (TBE) and malignant pleural effusion (MPE) is the commonest cause of exudative
pleural effusion in Malaysia. Early differentiation between these two diagnoses is essential
as TBE only requires drainage if symptomatic, whereas MPE would require tissue biopsy for
diagnosis confirmation and molecular profiling. However, both TBE and MPE present almost
similarly with lymphocytic exudates. Pleural fluid (Pf) indices such as adenosine deaminase
(ADA) may allow differentiation between these two entities in appropriate clinical
circumstances. However, Pf ADA may not readily be accessible in resource-limited regions and
the optimal cut-off varies depending on the local prevalence of tuberculosis. As a result,
TBE diagnosis in our region is still heavily dependent on the analysis of pre-existing
clinical demographic data and Pf parameters, where ultimately requiring pleural biopsy for a
confident clinical diagnosis.
Point-of-care predictors for TBE, such as ultrasound imaging appearance, may be helpful, but
have rarely been described. Previous studies have demonstrated that a complex septated
ultrasound pattern in lymphocytic pleural effusion is a potentially useful diagnostic
predictor to differentiate TBE from MPE with a positive predictive value of 94% and
likelihood ratio of 12.2 TBE diagnostic algorithms frequently include only clinical indices
with Pf parameters such as Pf differential cell count, ADA, protein and lactate dehydrogenase
(LDH). Incorporation of point-of-care ultrasound finding into the clinical diagnostic
algorithm has not been extensively explored.
TBE is the result of a delayed type IV hypersensitivity reaction to mycobacterial protein;
fibrin formation in the pleural cavity is largely driven by pro-inflammatory cytokines as
well as a reduction of fibrinolytic activity due to pleural inflammation. In contrast, MPE is
believed to be driven by a high degree of anaerobic metabolism leading to lactic acid
production, rather than an inflammatory response. These different pathogenic mechanisms in
TBE and MPE resulted in different pleural fluid parameters such as lower Pf glucose and pH
with higher Pf LDH level in MPE when compared to TBE. We believed that this principle may be
extrapolated to discriminative ultrasound findings between TBE and MPE.
The result from our retrospective pilot study found that the presence of echographic
septation had an adjusted odds ratio of 9.28 in prediction of TBE diagnosis from MPE. Along
with other clinical parameters (male gender, serum leucocyte counts 9 x 109/L or, pleural
fluid protein 50g/L or more), these parameters collectively report a diagnostic accuracy of
79.61% (95% CI 74.13-84.38) for TBE. In a previous study conducted in region with low
tuberculosis burden, pleural thickening of >1cm, pleural nodularity and diaphragmatic
thickening of >7mm on transthoracic ultrasound were highly suggestive of MPE. However, not
uncommonly, we observed similar pattern of pleural and diaphragmatic thickening in TBE
patients in our region as well.
As TBE is a hypersensitivity process with significant inflammatory response, we hypothesize
that echographic septation, in addition to pleural thickening and other sonographic findings,
may be a good indicator, as part of a clinical prediction model to discriminate TBE from MPE
in our region.
