Comparing N-terminal-proB-type Natriuretic Peptide With Other Criteria in Pleural Fluid Analysis

Comparing N-terminal-proB-type Natriuretic Peptide With Other Diagnostic Criteria in Discriminating Heart Failure-associated From Non-heart Failure-associated Pleural Effusions

To assess the discriminative properties of pleural fluid (PF) N-terminal-proB-type-natriuretic-peptide (NTproBNP) levels in identifying heart failure (HF)-associated pleural effusions (PE).

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Infections; Renal Failure; Cirrhosis; Fluid Overload; Pleural Effusion; Malignant Neoplasm; Hypoalbuminemia

Detailed Description

Objective: To assess the discriminative properties of pleural fluid (PF) N-terminal-proB-type-natriuretic-peptide (NTproBNP) levels in identifying heart failure (HF)-associated pleural effusions (PE).

Hypothesis to be tested: The PF NTproBNP levels are superior to existing methods including Light's criteria, serum/pleural fluid (S/PF) protein gradient, and albumin gradient, in identifying transudates and distinguishing between HF- and non-HF-associated PE.

Design and subjects: A prospective case-control study involving patients with PE requiring thoracentesis, caused by hypervolaemia due to HF, diseases other than HF, and patients with pleural effusion without hypervolaemia. Patient characteristics, PF results and effusion aetiology will be analysed. Patient outcomes will be followed up to 3 months to confirm the aetiology of PE. Clinical management of patients will not be affected.

Study instruments: PF of recruited patients will be analysed for albumin, protein, lactate dehydrogenase (LDH) levels and NTproBNP. The diagnosis of HF will be based on clinical features, serum NTproBNP and echocardiogram.

Main outcome measures: The performance of PF NTproBNP level in identifying HF-associated PE.

Data analysis: The PF NTproBNP level will be compared between effusions of different aetiologies. The optimal pleural fluid NTproBNP level with largest area under the receiver operating characteristic curve in identifying HF-associated PE will be determined. Performance of PF NTproBNP level in identifying HF-associated PE, and other biochemical criteria in identifying transudates will be compared. Echocardiographic findings will be correlated with the PF NTproBNP levels.

Expected results: The diagnostic performance of PF NTproBNP will be significantly better in identifying HF-associated effusion than other biochemical criteria.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Christopher Chan, MBChB; Phone Number: 35053396; Email: christopherchan@cuhk.edu.hk
• Study Contact Backup: Name: Ken KP Chan, MBChB; Phone Number: 35053396; Email: chankapang@cuhk.edu.hk

Study Locations

• Hong Kong
  • New Territories
    • Hong Kong, New Territories, Hong Kong, 0000
      • Recruiting
      • Prince of Wales Hospital
      • Contact: Christopher Chan, MBChB; Phone Number: 7607 85235052211; Email: christopherchan@cuhk.edu.hk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients who are admitted to the Department of Medicine & Therapeutics, Prince of Wales Hospital (PWH) who fulfil the inclusion and exclusion criteria

Description

Inclusion Criteria:

• Patients hospitalized for heart failure and pleural effusion
• Pleural tapping indicated for pleural fluid analysis.
• Aged 18 years old or above

Exclusion Criteria:

• History of intrapleural therapy (including talc and fibrinolytic) in the ipsilateral pleural space.
• History of surgical decortication or pleurodesis in the ipsilateral pleural space.
• Ipsilateral thoracic or cardiac surgery in the past 3 months.
• Failure to obtain informed consent due to the patient's refusal or cognitive impairment.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Heart Failure-Associated Pleural Effusion; Patients with pleural effusion with an underlying aetiology of heart failure
Non-Heart Failure, Fluid Overload-Associated Pleural Effusion; Patients with pleural effusion with an underlying aetiology of fluid overload excluding heart failure
Control group; Patients with pleural effusion due to exudative, or non-fluid overload causes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of the diagnostic performance of PF NTproBNP level in the diagnosis of HF-associated pleural effusions with other conventional biochemical criteria	Pleural fluid NTproBNP will be measured in patients with pleural effusion of various aetiologies including malignancy, pleural infection, heart failure and other causes of volume overload. The sensitivity and specificity of an elevated pleural fluid NTproBNP level in successfully identifying a pleural effusion due to underlying heart failure will be measured and compared against existing classification criteria for pleural effusion such as Light's Criteria, pleural-serum protein gradient or albumin gradient.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To measure the PF NTproBNP level in patients with pleural effusion of various aetiologies		24 months
Correlation of clinical factors that may affect the levels of pleural fluid NTproBNP such as echocardiographic features, presence of comorbidities, nutritional status, serum albumin level, levels of inflammatory markers and presence of infection	Clinical data of patients admitted to the hospital with pleural effusion will be measured and recorded. Statistical analysis will then be performed to evaluate for degree of correlation between the presence or severity of a clinical parameter, echocardiogram results e.g. severe valvular stenosis, or, e.g. presence of medical comorbidities or presence of concomitant infection, and the levels of NTproBNP identified in the patient's pleural fluid detected within same admission.	24 months
To correlate the PF NTproBNP levels with the echocardiographic features and prognosis of patients with heart failure		24 months

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong
• Collaborators: Roche Diagnostics

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2023
• Primary Completion (Estimated): November 30, 2025
• Study Completion (Estimated): November 30, 2025

Study Registration Dates

• First Submitted: March 16, 2023
• First Submitted That Met QC Criteria: March 31, 2023
• First Posted (Actual): April 4, 2023

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 18, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: cancer; echocardiography; infection; heart failure; tuberculosis; malignancy; pleural fluid; respiratory medicine
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Hematologic Diseases; Pleural Diseases; Blood Protein Disorders; Hypoproteinemia; Heart Failure; Neoplasms; Pleural Effusion; Hypoalbuminemia
• Other Study ID Numbers: NTProBNPPleuralEffusion1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Given patient data and privacy concerns, clinical data involving individual patients will not be shared. Data summary tables may later be published along with the research manuscript, and may be shared upon receipt of a reasonable request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No