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Trial registered on ANZCTR


Registration number
ACTRN12616000820404
Ethics application status
Approved
Date submitted
18/06/2016
Date registered
22/06/2016
Date last updated
22/06/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
PLeural Effusion and Symptom Evaluation (PLEASE) study on the pathophysiology of breathlessness in patients with symptomatic pleural effusions
Scientific title
PLeural Effusion and Symptom Evaluation (PLEASE) study on the pathophysiology of breathlessness in patients with symptomatic pleural effusions
Secondary ID [1] 289472 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
PLEASE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pleural Effusion 299153 0
Condition category
Condition code
Respiratory 299171 299171 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
The PLEASE study is a single centre prospective study of 150 patients with symptomatic pleural effusions that require therapeutic drainage. The study aims to identify key factors that underlie breathlessness in pleural effusion patients and develop predictors of improvement in breathlessness following effusion drainage. Participants will undergo evaluation pre- and post-effusion drainage to assess functional impairment at rest and during exercise, respiratory and other physiological responses and respiratory muscle mechanics.

Study Measurements include:
1. Baseline assessment (1.5 hours): All participants will be interviewed and examined prior to pleural drainage
i) Patient data – Demographics, comorbidities (e.g. COPD, heart disease), underlying cancer (type, stage and treatment, etc.) and relevant clinical data including cardio-pulmonary status (respiratory rate, heart rate, blood pressure and oxygen saturation by pulse oximetry) will be recorded.
ii) Pleural effusion characteristics – This will include the etiology of the effusion (if known) and the details of any prior pleural procedures.
iii) Measurement of breathlessness - Breathlessness will be assessed using three instruments; a) Visual Analogue Scale b) Dyspnea-12 Questionnaire and c) Modified Borg 0-10 scale. The VAS score is a validated measure of breathlessness in malignant pleural effusion and has been used in clinical trials involving MPE cohorts. The participant places a mark on the 100mm vertical scale to indicate the severity of their breathlessness. A score of 0mm indicates the most severe breathlessness. The Dyspnea-12 Questionnaire has demonstrated validity and reliability in COPD, asthma, interstitial lung disease and pulmonary arterial hypertension. It consists of 12 questions with physical and affective components. Each question is scored 0-3 points, with a total maximum score of 36 points indicating the most severe level of dyspnoea. The modified Borg scale 0-10 scale will be used to assess exertional dyspnoea evoked during the six-minute walk test.
iv) Measurement of functional capacity - Functional exercise capacity will be assessed using the 6-minute walk test. The distance walked, (i.e. 6MWD) will be expressed as an absolute distance (m) and as a percentage of the patient’s predicted 6MWD derived from a reference equation developed locally in healthy individuals.
v) Measurements of lung physiology: Detailed lung function including spirometry, lung volumes and gas transfer measurements will be performed as per the American Thoracic Society recommendations, provided that there are no contra-indications.
vii) Measurements of diaphragmatic morphology and function: Pleural ultrasound will be employed to assess diaphragm i) shape - normal (domed), flattened or inverted; and ii) movement - the zone of apposition (Zapp) of the diaphragm at the costo-phrenic angle will be measured.
viii) Radiological assessment of size of effusion: Effusions will be graded based on their radiographic appearance into five categories (where 0 = no effusion, and 5 = >75% of hemithorax). The presence of other radiographic abnormalities (eg. presence of mediastinal shift, trapped lung and fluid loculations) will also be recorded.

2. Pleural Drainage (1 hour): The fluid will be removed at a controlled rate to ensure patient safety as per international clinical guidelines. Data collected at the time of pleural drainage will include:
i) Total volume and duration of pleural fluid drainage.
ii) Measurements of pleural pressure using a digital manometer [Compass, Mirador Biomedical, Inc, Seattle, USA] - In a subgroup of patients, end-inspiratory and end-expiratory pleural pressure measurements will be recorded at opening pressure, after every 100mL of drainage up to 1000mLs and at closing pressure.
iii) Pleural fluid macroscopic appearance and biochemical analysis (e.g. pleural fluid pH and levels of protein, lactate dehydrogenase and glucose).

3. Repeat Testing (1.5 hours): The pre-drainage tests will be repeated between 24 and 36 hours after completion of drainage.

4. Follow up: Participants will be reviewed in the outpatient clinic 2 weeks after completing the testing. Data collected at this time point will only include any adverse events that may occur following the testing period. There will be no further scheduled study follow up visits following this.

The pre- and post-drainage parameters will be collected and compared to identify the key factors and mechanisms that correlate with symptom improvement. The pleural drainage procedure will be performed as part of standard clinical care and is not an intervention of the study.
Intervention code [1] 295055 0
Not applicable
Comparator / control treatment
All participants will serve as their own control. The post-drainage parameter will be compared to the pre-drainage parameter in the same patient.
Control group
Active

Outcomes
Primary outcome [1] 298654 0
Change in severity of breathlessness following drainage of pleural effusion.

Instruments:
1) 100mm Visual Analogue Scale at rest, b) Dyspnea-12 Questionnaire at rest and c) Modified Borg 0-10 scale at rest prior to the six-minute walk test and the peak level of breathlessness evoked during the test.
Timepoint [1] 298654 0
Assessments will be performed immediately pre-drainage of the pleural effusion and repeated 24-48 hours post-drainage.
Secondary outcome [1] 325001 0
Change in functional impairment at rest and during exercise following drainage of pleural effusion.

Instruments: 6-minute walk test. The distance walked, (i.e. 6MWD) will be expressed as an absolute distance (m) and as a percentage of the patient’s predicted 6MWD derived from a reference equation developed locally in healthy individuals.
Timepoint [1] 325001 0
Assessments will be performed immediately pre-drainage of the pleural effusion and repeated 24-48 hours post-drainage.
Secondary outcome [2] 325002 0
Changes in lung physiology following drainage of pleural effusion.

Instruments: Detailed lung function including spirometry, lung volumes and gas transfer measurements will be performed as per the American Thoracic Society recommendations, provided that there are no contra-indications.
Timepoint [2] 325002 0
Measurements will be made during tidal and inspiratory capacity breaths performed immediately pre-drainage of the pleural effusion and repeated 24-48 hours post-drainage.
Secondary outcome [3] 325003 0
Changes in diaphragmatic morphology and function following drainage of pleural effusion.

Instruments: Pleural ultrasound will be employed to assess a) diaphragm i) shape - normal (domed), flattened or inverted; and ii) movement - the zone of apposition (Zapp) of the diaphragm at the costo-phrenic angle will be measured.
Timepoint [3] 325003 0
Assessments will be performed immediately pre-drainage of the pleural effusion and repeated 24-48 hours post-drainage.
Secondary outcome [4] 325004 0
Changes in intra-pleural pressure during pleural effusion drainage.

Instruments: Digital manometer [Compass, Mirador Biomedical, Inc, Seattle, USA]
Timepoint [4] 325004 0
In a subgroup of patients, end-inspiratory and end-expiratory pleural pressure measurements will be recorded at opening pressure, after every 100mL of drainage up to 1000mLs and at closing pressure.

Eligibility
Key inclusion criteria
Suitable participants are those with symptomatic pleural effusion who require therapeutic pleural drainage (by needle aspiration, intercostal catheter (ICC) or indwelling pleural catheter (IPC)) as part of standard clinical care for management of the effusion and are able to provide written informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria include patients who:
1. are <18 years;
2. require urgent pleural drainage performed before pre-assessment protocol tests can be completed;
3. are unable to perform lung function and exercise tests, or are unable to comply with the protocol; and
4. are pregnant or lactating.

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Recruitment of 150 participants over a period of 24 months at a single centre based at Sir Charles Gairdner Hospital, Perth. Following on a recent internal audit, this enrolment target will be sufficient to capture effusions of varying sizes, chronicity and etiology (e.g. malignant, heart failure, hepatic hydrothorax). The sample size for this study was based on standard regression modelling strategies and is deemed sufficient given the number of predictors to be considered in the modelling.

Descriptive statistics of baseline characteristics of patients and measured responses will be provided. The magnitude and direction of the change pre- to post-drainage for the measured responses of breathlessness (VAS and Dyspnoea-12) and functional capacity (6-minute walk test) will be estimated using mean differences with 95% confidence intervals provided. Formal statistical modelling will take two approaches in order to (i) predict breathlessness response and (ii) model the mechanistic relationships between the changes in measurements pre to post procedure. Predicting breathlessness will be carried out using multiple linear regression to model the change in breathlessness and logistic regression, with ROC curve analyses, to model the dichotomous response of whether a clinically important change in breathlessness has been achieved. The analysis will investigate the impact of baseline measurements of numerous variables, including clinical data, lung physiology and measurements of diaphragmatic morphology and function along with demographics, thus enabling a prognostic index to be generated in order to identify patients and patient characteristics that would predict a positive outcome post effusion drainage. To model the mechanistic relationships between the change in measurements pre to post procedure, correlations and multiple linear regression analyses will be used to describe associations between the changes in the aforementioned variables along with changes in breathlessness variables, pleural effusion characteristics, diaphragmatic morphology and the total volume and duration of pleural drainage.

Whilst it is expected the missing data will be minimal, standard imputation techniques will be utilized if necessary, with regression analyses adjusted accordingly.

All data will be analysed using the R environment for statistical computing.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
10/02/2015
Date of last participant enrolment
Anticipated
31/12/2016
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
150
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 5993 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 13418 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 293839 0
Charities/Societies/Foundations
Name [1] 293839 0
Cancer Council of Western Australia
Country [1] 293839 0
Australia
Funding source category [2] 293884 0
Hospital
Name [2] 293884 0
Sir Charles Gairdner Research Advisory Group
Country [2] 293884 0
Australia
Primary sponsor type
Individual
Name
Professor YC Gary Lee
Address
School of Medicine, University of Western Australia, 533 Harry Perkins Building, QE II Medical Centre, Perth, WA 6009, Australia
Country
Australia
Secondary sponsor category [1] 292673 0
Individual
Name [1] 292673 0
Dr Rajesh Thomas
Address [1] 292673 0
Pleural Medicine Unit, Institute for Respiratory Health
Level 1, B Block, Sir Charles Gairdner Hospital
Hospital Ave, Nedlands, Western Australia 6009
Country [1] 292673 0
Australia
Secondary sponsor category [2] 292674 0
Individual
Name [2] 292674 0
Dr Maree Azzopardi
Address [2] 292674 0
Pleural Medicine Unit, Institute for Respiratory Health
Level 1, B Block, Sir Charles Gairdner Hospital
Hospital Ave, Nedlands, Western Australia 6009
Country [2] 292674 0
Australia
Secondary sponsor category [3] 292675 0
Individual
Name [3] 292675 0
Dr Sanjeevan MURUGANANDAN
Address [3] 292675 0
Pleural Medicine Unit, Institute for Respiratory Health
Level 1, B Block, Sir Charles Gairdner Hospital
Hospital Ave, Nedlands, Western Australia 6009
Country [3] 292675 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295281 0
Sir Charles Gairdner Group Human Research Ethics Committee
Ethics committee address [1] 295281 0
Ethics committee country [1] 295281 0
Australia
Date submitted for ethics approval [1] 295281 0
Approval date [1] 295281 0
19/06/2014
Ethics approval number [1] 295281 0
2014-079

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 66718 0
Prof YC Gary Lee
Address 66718 0
School of Medicine, UWA, 533 Harry Perkins Building, QE II Medical Centre, Perth, WA 6009, Australia.
Country 66718 0
Australia
Phone 66718 0
+61 410542490
Fax 66718 0
+61 8 93462816.
Email 66718 0
gary.lee@uwa.edu.au
Contact person for public queries
Name 66719 0
YC Gary Lee
Address 66719 0
School of Medicine, UWA, 533 Harry Perkins Building, QE II Medical Centre, Perth, WA 6009, Australia.
Country 66719 0
Australia
Phone 66719 0
+61 8 9346 1754
Fax 66719 0
+61 8 9346 1555
Email 66719 0
gary.lee@uwa.edu.au
Contact person for scientific queries
Name 66720 0
YC Gary Lee
Address 66720 0
School of Medicine, UWA, 533 Harry Perkins Building, QE II Medical Centre, Perth, WA 6009, Australia.
Country 66720 0
Australia
Phone 66720 0
+61 8 9346 1754
Fax 66720 0
+61 8 9346 1555
Email 66720 0
gary.lee@uwa.edu.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseProtocol of the PLeural Effusion and Symptom Evaluation (PLEASE) study on the pathophysiology of breathlessness in patients with symptomatic pleural effusions.2016https://dx.doi.org/10.1136/bmjopen-2016-013213
EmbaseThe pleural effusion and symptom evaluation (PLEASE) study of breathlessness in patients with a symptomatic pleural effusion.2020https://dx.doi.org/10.1183/13993003.00980-2019
N.B. These documents automatically identified may not have been verified by the study sponsor.