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Trial registered on ANZCTR


Registration number
ACTRN12620000519954
Ethics application status
Approved
Date submitted
13/03/2020
Date registered
28/04/2020
Date last updated
28/04/2020
Date data sharing statement initially provided
28/04/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Efficacy and Safety Outcomes of Drainage of Intensive Care Pleural Effusions
Scientific title
Efficacy and Safety Outcomes of Drainage of Intensive Care Pleural Effusions
Secondary ID [1] 299734 0
NIL KNOWN
Universal Trial Number (UTN)
Trial acronym
ESO-DICE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pleural Effusion 307513 0
Condition category
Condition code
Respiratory 306594 306594 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Drainage of the pleural fluid through an intercostal catheter inserted into the pleural space. This procedure will be performed by the treating intenisive care clinician who has been trained in this procedure. This procedure is considered a routine core skill for intensive care training. The exact technique (blunt dissection vs modified Seldinger technique) will be at the discretion of the treating intensivist. Complete evacuation of the fluid will be attempted and if that requires insertion of a second drainage tube that will be allowed as required as per normal practice. This treatment is externally obvious to all caring for the patient and therefore treatment allocation can not be concealed/blinded. The procedure takes 20 to 40 minutes on average.
Intervention code [1] 317178 0
Treatment: Other
Comparator / control treatment
Expectant management/observation. Patients in the control arm will be observed and given best supportive care. They will be allowed to undergo the intervention if deemed necessary by the treating doctor.
Control group
Active

Outcomes
Primary outcome [1] 305591 0
Co-Primary endpoints: i) Number of Pleural Effusion Related Serious Adverse Events (PERSAE’s) determined through clinical assessment and documentation in the medical record.

PERSAE’s will include all serious adverse events that may reasonably be considered to be related to the pleural effusion management strategy. All potential adverse events where there is lack of consensus between the treating clinician and the study investigators will be referred to an independent expert for the final decision. PERSAE’s may occur in either treatment arm, must be related to pleural effusion management and include:
a) Pneumothorax: Defined as unexpected new presence of pleural air on chest radiograph.
- Non-air leak pneumothorax (e.g. trapped lung/ex vacuo pneumothorax) that does not cause clinically apparent deterioration or any change in treatment will not be considered a serious adverse event
b) Bronchopleural Fistula: Defined by >24 hours of ongoing air leak evidenced by ongoing bubbling with each breath or increase in pneumothorax size in the event of chest drain occlusion >24 hours after diagnosis of pneumothorax
c) Dislodgement: Inadvertent removal of chest drain
d) Failure of Insertion: Inability to insert planned chest drain requiring abandonment of procedure after skin incision or needle insertion, resulting in a SAE
e) Bleeding which occurs as a result of pleural effusion management and requires action above and beyond applying pressure to the site
f) Hypotension requiring treatment with new or increased vasopressor and/or i.v. fluid. Either i) at the time of pleural effusion drainage or ii) as a result of inadequate management of the cause of the pleural effusion (e.g. sepsis, untreated bleeding)
g) Organ Puncture as a result of pleural procedure
h) Respiratory Failure: Worsening or new respiratory failure requiring escalation in oxygen delivery device or ventilation strategy
i) Missed diagnosis: Missing a diagnosis that may have resulted in a SAE
j) Any other SAE that may reasonably be attributable to either pleural management strategy

SAE will be defined as any events (Pleural effusion related, or not) that cause death or irreversible harm, or require treatment(s) to prevent these outcomes. Delayed drainage procedures undertaken in the control arm solely to manage effusion increase or ongoing ventilation requirement do not constitute PERSAE. However, if a delayed drainage procedure (>48 hours after randomisation) reveals an undiagnosed or untreated, life-threatening or serious condition, then that would constitute a PERSAE. All SAEs will be reported to the data and safety monitoring committee within 48 hours of detection.
Timepoint [1] 305591 0
The sooner of hospital discharge or 90 days
Primary outcome [2] 323292 0
ii) P:F ratio at 48 hours after randomisation.
P:F ratio is the ratio of the arterial PaO2/fraction of inspired O2 and is a measure of oxygenation adjusted for the amount of oxygen the patients is breathing. The PaO2 (partial pressure of arterial oxygen) is determined form routine analysis of arterial blood, usually in the intensive care from an arterial catheter. Only those patients that require an areterial catheter as part of their usual care will have arterial blood samples and these will be taken 6 hourly for the first 72 hours if required as per usual care. The FiO2 is simply the amount of oxygen provided and is routinely recorded at least hourly on the nursing observation charts.
Timepoint [2] 323292 0
48 hours after randomisation
Secondary outcome [1] 345846 0
The secondary endpoints for this trial are:
1. Number of patients suffering 1 or more PERSAE
This will be recorded immediately by the clinicain and/or trial staff in the SAE CRF

Timepoint [1] 345846 0
At the sooner of 90 days or hospital discharge
Secondary outcome [2] 381462 0
2. Non-pleural effusion related Serious Adverse Events (SAE). These will be recorded by the clinician and trial staff in a specific CRF
Timepoint [2] 381462 0
Daily until the sooner of 90 days or hospital discharge
Secondary outcome [3] 381463 0
3. All other adverse events as defined in the NHMRC guidelines. This will be recorded by the clinicain and trial staff in a specific CRF
Timepoint [3] 381463 0
Daily until the sooner of 90 days or hospital discharge
Secondary outcome [4] 381464 0
4. P:F ratios at other time points (6 hourly to 72 hours, or ICU discharge/removal of arterial cannula)
Timepoint [4] 381464 0
6 hourly to 72 hours, or ICU discharge/removal of arterial cannula
Secondary outcome [5] 381465 0
5. Change of diagnosis or treatment due to pleural drainage. This will be recorded daily whilst in ICU on the daily CRF.
Timepoint [5] 381465 0
Daily until ICU discharge
Secondary outcome [6] 381466 0
6. Number of pleural procedures - any procedure that enters the pleural space will require the completion of a drainage record form (CRF)
Timepoint [6] 381466 0
Daily until the sooner of hospital discharge or 90 days. This will be assessed from hospital records.
Secondary outcome [7] 381467 0
7. Ventilator-free days

Days not on a ventilator/ 90 days. This will be assessed from hospital records
Timepoint [7] 381467 0
at 90 days after randomisation
Secondary outcome [8] 381468 0
8. Hospital-free days

Days free from hospital/ 90 days. This will be assessed from hospital records
Timepoint [8] 381468 0
at 90 days from randomisation
Secondary outcome [9] 381469 0
Mortality. This will be assessed from hospital records
Timepoint [9] 381469 0
At the sooner of hospital discharge or 90 days from randomisation

Eligibility
Key inclusion criteria
Inclusion Criteria: Patients a) admitted to intensive care b) pleural effusion and c) clinician equipoise over drainage or expectant management.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria: In the opinion of treating clinician trial not in patient’s best interests; no clinical need for arterial catheterisation; age<18; inability to gain patient or next of kin consent; requiring ECMO.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Determination of eligibility for the trial will occur prior to knowing the randomisation outcome. Central randomisation will be performed through an online service (sealedenvelope.com)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
1:1 permuted block randomisation
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
The final sample size will be 48 patients randomised to drainage or expectant management in a 1:1 ratio. The distribution of participants amongst the 4 hospitals is expected to be approximately equal.

Based on the previous observational study the pooled mean P:F ratio at baseline was 244.2 (SD=100.1; SEM=10.61). The drainage group (DG) improved after 24 hours by mean 103.2 mmHg and the expectant management group (EM) by 5.0 mmHg. This implies expected means in the proposed study at 24 hours after treatment of 347.4 (DG) and 249.2 (EM). The sample size that will give 90% power to statistically detect this difference in P:F ratio at 24 hours with an a (type one error rate) value of 0.05 is calculated to be 44 (22 in each group). Allowing for a 10% loss to follow up/withdrawal rate the required sample size to ensure power to detect a statistically significant difference in P:F ratio is 48 patients. 

Both intention-to-treat and per protocol analyses are planned. Response to treatment will be assessed using P:F ratio analysed as a continuous variable compared using either the student’s t-test (if parametric) or the Mann-Whitney U-test (if non-parametric). The frequencies of adverse events and mortality will be compared amongst the 2 groups using Chi-square tests. The number of ventilator-free and hospital-free days will be compared amongst groups using the Mann-Whitney U-test for non-parametric data.

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 in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 10761 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [2] 10762 0
Royal Perth Hospital - Perth
Recruitment hospital [3] 10763 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [4] 15111 0
St John of God Midland Public Hospital - Midland
Recruitment hospital [5] 15112 0
St John of God Hospital, Subiaco - Subiaco
Recruitment hospital [6] 15113 0
St John of God Hospital, Murdoch - Murdoch
Recruitment postcode(s) [1] 22489 0
6009 - Nedlands
Recruitment postcode(s) [2] 22490 0
6000 - Perth
Recruitment postcode(s) [3] 22491 0
6150 - Murdoch
Recruitment postcode(s) [4] 28406 0
6056 - Midland
Recruitment postcode(s) [5] 28407 0
6008 - Subiaco

Funding & Sponsors
Funding source category [1] 299276 0
Government body
Name [1] 299276 0
National Health and Medical Research Council
Address [1] 299276 0
16 Marcus Clarke st
Canberra
ACT 2601
Country [1] 299276 0
Australia
Funding source category [2] 304206 0
Charities/Societies/Foundations
Name [2] 304206 0
Raine Medical Research Foundaton
Address [2] 304206 0
Suite 24
Hollywood Specialist Centre
95 Monash Ave
Nedlands
WA6009
Country [2] 304206 0
Australia
Primary sponsor type
University
Name
University of Western Australia
Address
UWA - Institute for Respiratory Health
Ground floor E block
Sir Charles Gairdner Hospital
Nedlands
WA 6009
Country
Australia
Secondary sponsor category [1] 304441 0
Hospital
Name [1] 304441 0
St John of God Midland Hospital
Address [1] 304441 0
St John of God Hospital
1 Clayton St
Midland WA 6056
Country [1] 304441 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300188 0
Sir Charles Gairdner and Osborne Park Group Human Research and Ethics Committe
Ethics committee address [1] 300188 0
Sir Charles Gairdner Hospital
Nedlands
WA 6009
Ethics committee country [1] 300188 0
Australia
Date submitted for ethics approval [1] 300188 0
Approval date [1] 300188 0
18/12/2017
Ethics approval number [1] 300188 0

Summary
Brief summary
The ESODICE trial is a Phase 2 open label randomised trial of drainage of pleural effusion in patients admitted to an intensive care unit. Coprimary endpoints are: a) safety, determined by rates of pleural effusion related serious adverse events at the earlier of 90 days or hospital discharge; b) efficacy, defined as statistically significant improvement in P:F ratio at 48 hours compared to randomisation.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 82846 0
Dr Edward Fysh
Address 82846 0
St John of God Midland Hospital
1 Clayton st
Midland
WA 6056
Country 82846 0
Australia
Phone 82846 0
+61 8 94624000
Fax 82846 0
Email 82846 0
Edward.Fysh@sjog.org.au
Contact person for public queries
Name 82847 0
Dr Edward Fysh
Address 82847 0
St John of God Midland Hospital
1 Clayton st
Midland
WA 6056
Country 82847 0
Australia
Phone 82847 0
+61 8 9462 4000
Fax 82847 0
Email 82847 0
Edward.Fysh@sjog.org.au
Contact person for scientific queries
Name 82848 0
Dr Edward Fysh
Address 82848 0
St John of God Midland Hospital
1 Clayton st
Midland
WA 6056
Country 82848 0
Australia
Phone 82848 0
+61 8 9462 4000
Fax 82848 0
Email 82848 0
Edward.Fysh@sjog.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Ethical approval
How or where can supporting documents be obtained?
Type [1] 5575 0
Ethical approval
Citation [1] 5575 0
Link [1] 5575 0
Email [1] 5575 0
Other [1] 5575 0
Summary results
No Results