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Trial registered on ANZCTR


Registration number
ACTRN12621001230842
Ethics application status
Approved
Date submitted
5/07/2021
Date registered
13/09/2021
Date last updated
13/09/2021
Date data sharing statement initially provided
13/09/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Parapneumonic effusion and empyema: aetiology and clinical outcome evaluation in Canterbury. The PEACE study.
Scientific title
Parapneumonic effusion and empyema: current aetiology, new biomarkers and clinical outcome evaluation in Canterbury. The PEACE study. A prospective cohort study in adults with pleural infections.
Secondary ID [1] 304695 0
None
Universal Trial Number (UTN)
Trial acronym
PEACE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Parapneumonic effusion 322679 0
Empyema 322680 0
Pleural infection 322681 0
Condition category
Condition code
Respiratory 320293 320293 0 0
Other respiratory disorders / diseases
Infection 320639 320639 0 0
Other infectious diseases

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
This single centre prospective cohort study aims to assess the current aetiology, patients’ characteristics, complications, (new) biomarkers, clinical outcome, and quality of life in patients with parapneumonic effusion or empyema.

All adult patients admitted to the respiratory medicine ward at Christchurch Hospital with empyema or parapneumonic effusion and who meet all inclusion and no exclusion criteria will be invited to participate. Participants will be recruited between August 2021 and August 2023, with a longitudinal follow-up for 1 year.

The majority of data will be obtained through standard care, using the Canterbury Hospital HealthPathway of ‘Pleural Effusion’. Data will be collected from the patient’s electronic hospital file and the patient during admission, with the use of a patient questionnaire.

During the study, we will take additional blood and pleural fluid samples. Samples will be taken only once, at baseline, during hospital admission.

The quality of life and symptom measurements are additional as well to the standard care. The patient will be asked to complete questionnaires on quality of life and symptoms on admission, at discharge, and during follow-up after discharge (1, 6, and 12 months). During follow-up, based on individual preferences, the participant will be sent the questionnaires by mail with a return envelope or by email via Qualtrics.
Intervention code [1] 321071 0
Diagnosis / Prognosis
Comparator / control treatment
N/A
Control group
Uncontrolled

Outcomes
Primary outcome [1] 328148 0
Current aetiology of parapneumonic effusion and empyema in Canterbury based on conventional culture of pleural fluid
(composite primary outcome)
Timepoint [1] 328148 0
T1. Baseline - hospital admission: samples for pleural fluid culture will be taken during standard diagnostic care in participants with a clinical suspicion of a pleural infection.
Primary outcome [2] 328150 0
Current aetiology of parapneumonic effusion and empyema in Canterbury, based on additional nucleic acid amplification tests (NAAT) on pleural fluid
(composite primary outcome)
Timepoint [2] 328150 0
T1. Baseline - hospital admission: samples for NAAT will be taken during standard diagnostic care in participants with a clinical suspicion of a pleural infection. NAAT analyses will be done in batches.
Primary outcome [3] 328895 0
Exploratory evaluation of pleural fluid inflammatory response markers and pleural injury markers, and neutrophil function and activity on their role in classification and prognostication in empyema and parapneumonic effusion (composite outcome).
Eg. myeloperoxidase, procalcitonin, proADM
Timepoint [3] 328895 0
T1. Baseline - hospital admission: pleural fluid samples taken at baseline
Analyses will be done in batches
Secondary outcome [1] 399058 0
Added diagnostic yield of NAAT in comparison to conventional culture, determined by the improvement of microbiological yield based on the specificity of NAAT compared to conventional culture
Timepoint [1] 399058 0
Based on the samples taken at T1. Baseline - hospital admission: samples for pleural fluid culture and NAAT will be taken during standard diagnostic care in participants with a clinical suspicion of a pleural infection.
Secondary outcome [2] 399059 0
Exploratory evaluation of blood biomarkers (inflammatory response markers and pleural injury markers, and neutrophil function and activity) in classifying and prognostication in empyema and parapneumonic effusion. (composite, primary outcome)
Eg. myeloperoxidase, procalcitonin, proADM
Timepoint [2] 399059 0
T1. Baseline - hospital admission: blood samples taken at baseline
Analyses will be done in batches
Secondary outcome [3] 399060 0
Recovery of symptoms, assessing thoracic pain with the use of the Visual Analog Scale (VAS)
Timepoint [3] 399060 0
T1. Baseline - hospital admission - 2 questionnaires, symptoms at admission and before admission (-30days, based on recall)
T2. At discharge
T3. 1 month after discharge
T4. 6 months after discharge
T5. 12 months after discharge
Secondary outcome [4] 399061 0
Quality of life during and after admission, assessed by the short Form-36 Health Survey questionnaire

Timepoint [4] 399061 0
T1. Baseline - hospital admission
T2. At discharge
T3. 1 month after discharge
T4. 6 months after discharge
T5. 12 months after discharge
Secondary outcome [5] 399892 0
Current aetiology of parapneumonic effusion in Canterbury based on conventional culture of pleural fluid
Timepoint [5] 399892 0
T1. Baseline - hospital admission: samples for pleural fluid culture will be taken during standard diagnostic care in participants with a clinical suspicion of a pleural infection.
Secondary outcome [6] 399893 0
Current aetiology of empyema in Canterbury based on conventional culture of pleural fluid
Timepoint [6] 399893 0
T1. Baseline - hospital admission: samples for pleural fluid culture will be taken during standard diagnostic care in participants with a clinical suspicion of a pleural infection.
Secondary outcome [7] 399896 0
Health outcomes of patients with empyema and parapneumonic in Canterbury, assessed by re-admission rate (within 30 days after discharge), determined by review of medical records
Timepoint [7] 399896 0
T3. 1 month after discharge
Secondary outcome [8] 399897 0
Health outcomes of patients with empyema and parapneumonic in Canterbury, assessed by
mortality rate (30-day and 12 months), determined by review of medical records
Timepoint [8] 399897 0
T2. At discharge
T3. 1 month after discharge
T4. 6 months after discharge
T5. 12 months after discharge
Secondary outcome [9] 399898 0
Health outcomes of patients with empyema and parapneumonic in Canterbury, assessed by
complications during admission (i.e. bronchopleural fistulae, ICU admission, invasive ventilation) determined by review of medical records
Timepoint [9] 399898 0
T2. At discharge
Secondary outcome [10] 399899 0
Health outcomes of patients with empyema and parapneumonic in Canterbury, assessed by
radiographic outcomes, resolution of abnormalities, determined by review of medical records
Timepoint [10] 399899 0
T1. Baseline - hospital admission
T2. At discharge
T3. 1 month after discharge
T4. 6 months after discharge
T5. 12 months after discharge
Secondary outcome [11] 399900 0
Recovery of symptoms, assessing dyspnoea with the modified Medical Research Council (mMRC) breathlessness scale)

Timepoint [11] 399900 0
T1. Baseline - hospital admission - 2 questionnaires, symptoms at admission and before admission (-30days, based on recall)
T2. At discharge
T3. 1 month after discharge
T4. 6 months after discharge
T5. 12 months after discharge
Secondary outcome [12] 399901 0
Recovery of symptoms, assessed by the community-acquired pneumonia symptom questionnaire (CAP-sym)
Timepoint [12] 399901 0
T1. Baseline - hospital admission - 2 questionnaires, symptoms at admission and before admission (-30days, based on recall)
T2. At discharge
T3. 1 month after discharge
T4. 6 months after discharge
T5. 12 months after discharge
Secondary outcome [13] 400821 0
Health outcomes of patients with empyema and parapneumonic in Canterbury, assessed by length of hospital stay (in days), determined by review of medical records
Timepoint [13] 400821 0
T1. Baseline - hospital admission
T2. At discharge

Eligibility
Key inclusion criteria
- Age > 18 years
- Clinical suspicion of parapneumonic effusion (simple and complicated) or empyema.
- Clinically indication pleural aspiration or drainage
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Earlier enrolment to the study
- Not able to provide informed consent
- Treatment failure or complication from recent medical intervention (e.g. pleural drainage, VATS)

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Baseline characteristics and aetiology:
For demographic and clinical variables at baseline, data will be presented as median (IQR) or means (SD) for continuous variables and number (%) for categorical variables.
Regarding aetiology results, we will use the nomenclature and classification used by our microbiology department. Furthermore, we will also group the results into binary test results (positive vs negative culture) and calculate the sensitivity. In case of additional enhanced diagnostic testing through nuclear acid amplification tests, we will assess the added value of these tests to standard culture by calculating the improved sensitivity for detecting causative pathogens.

Biomarkers:
The ability of the different biomarkers (pleural fluid and blood) to accurately differentiate between empyema, simple and complicated parapneumonic effusion, clinical management, and clinical outcomes will be studied with the use of receiver-operating characteristics (ROC) analyses. The ROC curves will be used to demonstrate the decision values of various cut-off points for the different biomarkers. Univariate logistic regression will be performed to test the association for each biomarker with the presence of empyema, complicated parapneumonic effusion (CPPE), or simple parapneumonic effusion (SPPE). Significant predictors from these analyses will be used for a multivariate logistic regression analysis to assess the independent predictive value. A p-value of <0.05 will be considered statistically significant.

Clinical outcomes:
We will use univariate and multivariate logistic regression analyses to identify independent predictors of the different aspects of patients’ outcomes.
The change from baseline to 12 months in the quality of life and symptom measurements will be calculated by analysis of covariance (ANCOVA) adjusted for the baseline measurements. To compare the proportion of patients (empyema vs CPPE vs SPPE) with either clinical or quality-of-life improvement, stability, or decline, a binomial test will be performed and presented differences as a percentage with accompanying 95% CI. Categorical data between groups will be calculated with the chi-square test. P- values of <0.05 will be significant.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 23941 0
New Zealand
State/province [1] 23941 0
Canterbury

Funding & Sponsors
Funding source category [1] 309062 0
Charities/Societies/Foundations
Name [1] 309062 0
W.H. Travis Trust
Address [1] 309062 0
C/o Ashton Wheelans & Hegan Limited 4th Floor, 127 Armagh Street Christchurch
Christchurch 9999
Country [1] 309062 0
New Zealand
Primary sponsor type
University
Name
University of Otago, Christchurch
Address
2 Riccarton Avenue, Christchurch Central City, Christchurch 8011
Country
New Zealand
Secondary sponsor category [1] 310011 0
None
Name [1] 310011 0
Address [1] 310011 0
Country [1] 310011 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308940 0
Northern A Health and Disability Ethics Committee
Ethics committee address [1] 308940 0
Ministry of Health
133 Molesworth Street
PO Box 5013
Wellington
6011
Ethics committee country [1] 308940 0
New Zealand
Date submitted for ethics approval [1] 308940 0
24/02/2021
Approval date [1] 308940 0
28/06/2021
Ethics approval number [1] 308940 0
21/NTA/35

Summary
Brief summary
Pleural effusion is a build-up of fluid in the pleural space, the thin space between the lungs and the inner surface of the chest wall. Normally, there is a small amount of fluid in this space. However, due to many different reasons, the fluid in the pleural space can accumulate. Among these causes are pleural infectious effusions, specifically
(simple and complicated) parapneumonic effusion and empyema.
Parapneumonic effusions and empyema are increasing in incidence and associated with high morbidity and mortality. Empyema carries a case-fatality ratio of up to 20% overall and up to 42% in patients with significant comorbidities, such as lung cancer.

This prospective cohort study aims to assess the current aetiology, patients’ characteristics, new biomarkers, clinical outcomes, and quality of life in patients with parapneumonic effusion or empyema. To be able to better understand the opportunities for improving diagnostics and outcomes in future patients with empyema and parapneumonic pleural effusion.

In addition, we aim to establish a biobank for future unspecified research of participant data and samples enrolled in the PEACE study.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 112402 0
Dr Margot (J.M.) de Koning Gans
Address 112402 0
University of Otago, Christchurch
Department of Medicine
2 Riccarton Avenue, Christchurch Central City, Christchurch 8011
Country 112402 0
New Zealand
Phone 112402 0
+64 3 364 1116
Fax 112402 0
Email 112402 0
margot.dekoninggans@postgrad.otago.ac.nz
Contact person for public queries
Name 112403 0
Dr Margot (J.M.) de Koning Gans
Address 112403 0
University of Otago, Christchurch
Department of Medicine
2 Riccarton Avenue, Christchurch Central City, Christchurch 8011
Country 112403 0
New Zealand
Phone 112403 0
+64 3 364 1116
Fax 112403 0
Email 112403 0
margot.dekoninggans@postgrad.otago.ac.nz
Contact person for scientific queries
Name 112404 0
Dr Margot (J.M.) de Koning Gans
Address 112404 0
University of Otago, Christchurch
Department of Medicine
2 Riccarton Avenue, Christchurch Central City, Christchurch 8011
Country 112404 0
New Zealand
Phone 112404 0
+64 3 364 1116
Fax 112404 0
Email 112404 0
margot.dekoninggans@postgrad.otago.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Only de-identified data collected during the PEACE study of participants who consented to participate in the Biobank as well will be available. No tissue samples will be available.
When will data be available (start and end dates)?
Beginning 3 months following main results publication from the PEACE study. No end date determined.
Available to whom?
This future research will need to be approved by an appropriate ethical review committee and our research team.
Available for what types of analyses?
All types of analyses that are approved by an appropriate ethical review committee and our research team.
How or where can data be obtained?
By contacting the principal investigator via e-mail:
Margot.dekoninggans@postgrad.otago.ac.nz
What supporting documents are/will be available?
No other documents available
Summary results
No Results