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Trial registered on ANZCTR


Registration number
ACTRN12621001356853
Ethics application status
Approved
Date submitted
24/08/2021
Date registered
7/10/2021
Date last updated
4/04/2024
Date data sharing statement initially provided
7/10/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Extubation Of preterm infants: The Diagnostic utility of UltraSound (EXODUS)
Scientific title
Can point of care ultrasound predict extubation failure in preterm infants?
A prospective observational study: Study protocol
Secondary ID [1] 305290 0
None
Universal Trial Number (UTN)
Trial acronym
EXODUS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prematurity 323340 0
Respiratory distress syndrome 323341 0
Condition category
Condition code
Respiratory 320911 320911 0 0
Other respiratory disorders / diseases
Reproductive Health and Childbirth 320912 320912 0 0
Complications of newborn

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Mechanically ventilated infants will be assessed for eligibility for study recruitment. Infants will either be extubated to nasal continuous positive airway pressure (nCPAP), non-invasive positive pressure ventilation (NIPPV), nasal high flow therapy (nHFT) or to no respiratory support at the treating team’s discretion. Infant will receive ultrasounds before and after extubation as described below.

Lung ultrasound

Infants will receive a LUS within 1 hour of extubation and 30 minutes after extubation, then daily for 72 hours post extubation. Subsequent LUS will be performed within 6 hours of the original extubation time. LUS images will be reported and assigned global aeration scores, quadrant specific scores of atelectasis and measurements of depth of atelectasis if present. The treating team will remain blind to LUS findings. LUS images will be obtained using a GE Venue Go or Vivid S6 or Venue 50 (GE Healthcare, USA) ultrasound system with a “hockey stick,” L8-18i linear transducer set at a depth of 2cm and a gain of 60. Three second video clips will be acquired. M-mode imaging will be performed with each ultrasound clip with the m-mode cursor being applied between the rib spaces to capture pleural sliding. Each LUS will take approximately 5 minutes.

Diaphragm ultrasound

Diaphragm ultrasound (DUS) will be performed with the infant in the supine position. The treating team will remain blinded to the DUS findings. The probe will be placed in the midclavicular line in the right subcostal region. Only the right hemidiaphragm will be studied due to the limited acoustic window the left hemidiaphragm. Peak velocity of right diaphragmatic contraction will be obtained via tissue doppler imaging of the right hemidiaphragm . Diaphragm thickness will be measured using m-mode imaging. DUS will be performed at the same time points as LUS. Each DUS will take approximately 5 minutes.

Vocal cord ultrasound

A single Vocal cord ultrasound (VUS) will be performed 24 hours after extubation with infants in the supine position. The treating team will remain blind to the VUS findings.
VUS will be obtained a “hockey stick,” L8-18i linear transducer. Normal vocal cord function will be determined by the presence of complete adduction (centrally inverted “T” formed by the vocal cord folds) and complete abduction (centrally inverted “V. For an objective measurement, we will measure the maximum distance of abduction at the base of the vocal cords. VUS will take approximately 5 minutes.
Intervention code [1] 321515 0
Diagnosis / Prognosis
Comparator / control treatment
No Control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 328697 0
The ability of the LUS aeration score derived from combined anterior and lateral imaging to predict extubation failure (EF) as defined as replacement of an endotracheal tube which will be determined by review of the medical records and communication with the treating team.
Timepoint [1] 328697 0
1. 72 hours (primary timepoint)
2. 24 hours post extubation
3. 48 hours post extubation
4. 7 days post extubation (outcome only, no ultrasound)
Secondary outcome [1] 399987 0
The ability of the LUS aeration score derived from lateral imaging only to predict EF as defined by the replacement of an endotracheal tube which will be determined by review of the medical records and communication with the treating team.
Timepoint [1] 399987 0
1. 72 hours
2. 24 hours post extubation
3. 48 hours post extubation
4. 7 days post extubation (outcome only, no ultrasound)
Secondary outcome [2] 399988 0
The ability of the LUS aeration score derived from the combined anterior, lateral and posterior imaging to predict EF which will be determined by review of the medical records and communication with the treating team.
Timepoint [2] 399988 0
1. 72 hours post extubation
2. 24 hours post extubation
3. 48 hours post extubation
4. 7 days post extubation (outcome only, no ultrasound)
Secondary outcome [3] 400112 0
The correlation between LUS aeration score and measurement of
1. depth of atelectasis from the anterior, lateral and posterior regions measured in millimetres from the pleural surface to resumption of the LUS artefact pattern and;
2. Respiratory support requirements which will be determined by the required mean airway pressure (centimetres of water), fraction of inspired oxygen (FiO2 [%]) and oxygen saturation to FiO2 ratio (unitless) as determined from review of the medical records
Timepoint [3] 400112 0
1. 60 minutes pre extubation
2. 30 minutes post extubation
3. 24 hours post extubation
4. 48 hours post extubation
5. 72 hours post extubation
Secondary outcome [4] 400113 0
The ability of measurement of diaphragmatic excursion (m/s) and diaphragm thickness (mm) obtained from diaphragm ultrasound to predict EF which will be determined by review of the medical records and communication with the treating team.
Timepoint [4] 400113 0
1. 72 hours post extubation
2. 24 hours post extubation
3. 48 hours post extubation
4. 7 days post extubation (outcome only, no ultrasound)
Secondary outcome [5] 400883 0
The sonographic appearance of the vocal cords measured by vocal cord ultrasound 24 hours post extubation
Timepoint [5] 400883 0
24 hours post extubation only

Eligibility
Key inclusion criteria
All infants born < 32 weeks and/or < 1250g who are mechanically ventilated for > 4 hours will be considered eligible
Minimum age
4 Hours
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Congenital lung malformations including congenital diaphragmatic hernia
• Genetic conditions that affect respiratory drive or effort
• Congenital upper airway anomalies.
• Previous participation in EXODUS

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
Sample Size Estimation

Assuming an extubation failure rate of 30% in infants < 32 weeks gestation, and a predicted sensitivity of LUS to predict extubation failure of 85%, a sample size of 100 patients would yield a 95% confidence interval of 65%-94%.

Methods of analysis

Baseline characteristics will be presented as means and standard deviation of the mean or median and interquartile range if normally or non-normally distributed. Continuous variables will be compared by Student’s t test if normally distributed and by Mann-Whitney U test if skewed. Categorical data will be assessed using the Fisher two tailed exact test. Significance will be set at p < 0.05.

Primary outcome:

The area under the curve (AUC) of the ROC analysis will be used to determine the accuracy of LUS to predict extubation failure. The AUC, sensitivity and specificity together with 95% CIs will be reported.

Secondary outcome:

Each predictor of extubation failure will be presented as the calculated AUC, sensitivity and specificity, with 95% confidence intervals. Pearson’s or Spearman’s Correlation coefficients of LUS aeration scores with respiratory support requirements depending on distribution.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/11/2021
Actual
8/11/2021
Date of last participant enrolment
Anticipated
27/09/2024
Actual
13/07/2023
Date of last data collection
Anticipated
4/10/2024
Actual
17/02/2024
Sample size
Target
100
Accrual to date
Final
100
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 20335 0
The Royal Women's Hospital - Parkville
Recruitment hospital [2] 20336 0
Sunshine Hospital - St Albans
Recruitment postcode(s) [1] 35088 0
3052 - Parkville
Recruitment postcode(s) [2] 35089 0
3021 - St Albans

Funding & Sponsors
Funding source category [1] 309505 0
Government body
Name [1] 309505 0
National Health and Research Council
Country [1] 309505 0
Australia
Primary sponsor type
Hospital
Name
The Royal Women's Hospital
Address
20 Flemington Road, Parkville, VIC 3052
Country
Australia
Secondary sponsor category [1] 310486 0
None
Name [1] 310486 0
Address [1] 310486 0
Country [1] 310486 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309291 0
The Royal Children's Hospital Human Research Ethics Committee
Ethics committee address [1] 309291 0
50 Flemington Road, Parkville VIC 3052
Ethics committee country [1] 309291 0
Australia
Date submitted for ethics approval [1] 309291 0
01/07/2021
Approval date [1] 309291 0
18/08/2021
Ethics approval number [1] 309291 0
HREC/74060/RCHM-2021-278108(v3)

Summary
Brief summary
Babies who are born early (premature babies) often require help with their breathing. Some premature babies will require a breathing tube (intubation) and help from a breathing machine (ventilator). A ventilator helps babies to stay alive but may damage their lungs. To minimise this damage, we try to take the breathing tube out (extubate) as soon as possible. Unfortunately, some babies will not succeed and require the breathing tube to be put back in (reintubation). These babies are likely to be sicker in the long term than those who are successfully extubated. There are few tools available to help predict which babies will fail extubation.

Ultrasound is a form of imaging that uses reflected sound to create an image of different parts of the body. It is safe, painless and does not use radiation. Ultrasound can be used to image the lungs of babies. We are exploring whether a lung ultrasound performed before a baby is extubated will help us predict extubation failure. We are also exploring if repeated lung ultrasound will give us more information on how a baby’s lungs behave after being extubated. Additionally, we are exploring two new types of ultrasound, one of a baby’s diaphragm (the main muscle of breathing) and one of their vocal cords.

In this study, we will perform and ultrasound of a baby’s lungs and diaphragm before and after extubation and then daily for the next three days. We will also perform one vocal cord ultrasound 24 hours after extubation. We will use this information to see if we can predict which babies will require reintubation.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 113650 0
Dr Arun Sett
Address 113650 0
Newborn Research Centre
20 Flemington Road, Parkville, VIC 3052
Country 113650 0
Australia
Phone 113650 0
+61405491595
Fax 113650 0
Email 113650 0
[email protected]
Contact person for public queries
Name 113651 0
Arun Sett
Address 113651 0
Newborn Research Centre, The Royal Women's Hospital
50 Flemington Road, Parkville, VIC 3052
Country 113651 0
Australia
Phone 113651 0
+61405491595
Fax 113651 0
Email 113651 0
[email protected]
Contact person for scientific queries
Name 113652 0
Arun Sett
Address 113652 0
Newborn Research Centre, The Royal Women's Hospital
50 Flemington Road, Parkville, VIC 3052
Country 113652 0
Australia
Phone 113652 0
+61405491595
Fax 113652 0
Email 113652 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data collected during the study after deidentification
When will data be available (start and end dates)?
Data will be available to researchers beginning 3 months and ending 23 years after article publication who provide a methodological sound proposal
Available to whom?
Data will be made available to researchers upon reasonable request for approved research projects. Requests should be directed to the principal investigator (AS)
Available for what types of analyses?
Institutionally and ethically approved research projects
How or where can data be obtained?
Direct contact with the PI via email [email protected]


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
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