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Trial registered on ANZCTR


Registration number
ACTRN12621001119886
Ethics application status
Approved
Date submitted
30/06/2021
Date registered
23/08/2021
Date last updated
23/08/2021
Date data sharing statement initially provided
23/08/2021
Type of registration
Retrospectively registered

Titles & IDs
Public title
CUMULUS: Comparing Ultrasound Markers of Under recruited Lung in preterm infants on respiratory Support
Scientific title
Comparing an ultrasound derived lung aeration score to radiological diagnosis of underinflation and respiratory support requirements in preterm infants.
Secondary ID [1] 304470 0
None
Universal Trial Number (UTN)
Trial acronym
CUMULUS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prematurity 322303 0
Respiratory distress syndrome 322304 0
Under recruited lung 322306 0
Condition category
Condition code
Reproductive Health and Childbirth 319974 319974 0 0
Complications of newborn
Respiratory 319975 319975 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
Preterm infants born < 32 weeks gestation and > 24 hours of age who are receiving a chest radiograph for any indication will receive a lung ultrasound immediately before the chest radiograph. Images of the anterior and lateral lung regions will be obtained for every infant. If positioned prone prior to the chest radiograph, posterior images will also be required. Ultrasound scans will take approximately 10 minutes. Ultrasound images will be obtained using a GE Venue 50 (GE, USA) or Philips Epiq 7 (Koninklijke Philips, Netherlands) ultrasound machine and a “hockey stick,” L8-18i linear transducer set at a depth of 2cm and a gain of 60. Six second video loops will be recorded. Lung ultrasounds will be blindly reported using a previously validated lung ultrasound scoring system. Chest radiographs will be blindly reported by a Paediatric Radiologist.

Oxygen saturation index (OSI) will be determined at the time of the ultrasound scan. This measure is derived from the respiratory support settings and measured oxygen saturations. This does not involve extra handling for the infants.
Intervention code [1] 320821 0
Diagnosis / Prognosis
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 327850 0
The sensitivity and specificity of an ultrasound derived lung aeration score for radiological diagnosis of under-inflation on chest radiograph as defined by the presence of < 8 posterior ribs visualised at the level of the diaphragm
Timepoint [1] 327850 0
Lung ultrasound performed immediately before chest radiograph
Primary outcome [2] 327851 0
The inter and intra observer variability of the lung ultrasound (LUS) derived lung aeration score performed by two investigators at least 1 months apart
Timepoint [2] 327851 0
Lung ultrasound performed immediately before chest radiograph
Secondary outcome [1] 396782 0
The sensitivity and specificity of a LUS aeration score with radiological evaluation of lung inflation as defined by number of posterior ribs seen on chest radiograph
Timepoint [1] 396782 0
Lung ultrasound performed immediately before chest radiograph
Secondary outcome [2] 396783 0
The correlation between quadrant specific ultrasound derived aeration score and radiological diagnosis of quadrant specific atelectasis
Timepoint [2] 396783 0
Lung ultrasound performed immediately before chest radiograph
Secondary outcome [3] 396784 0
The inter and intra-observer agreement of the quadrant specific LUS derived aerations scores
Timepoint [3] 396784 0
Lung ultrasound images reported twice by two investigators at least 1 month apart, blinded to clinical information.
Secondary outcome [4] 396787 0
The correlation between quadrant specific LUS diagnosis of atelectasis (yes/no) and quadrant specific chest x-ray (CXR) diagnosis of atelectasis
Timepoint [4] 396787 0
Lung ultrasound performed immediately before chest radiograph
Secondary outcome [5] 396788 0
The inter and intra-observer agreement of a LUS diagnosis of atelectasis
Timepoint [5] 396788 0
Lung ultrasound images reported twice by two investigators at least 1 month apart.
Secondary outcome [6] 396789 0
The correlation between a global LUS aeration score and severity of respiratory illness assessed by the Oxygen Saturation Index (OSI) at the time of the LUS.
Timepoint [6] 396789 0
Lung ultrasound performed immediately before chest radiograph
Secondary outcome [7] 396865 0
The sensitivity and specificity of the measurement of atelectasis in millimetres with radiological diagnosis of under-inflation on chest radiograph as defined by the presence of < 8 posterior ribs visualised at the level of the diaphragm
Timepoint [7] 396865 0
Lung ultrasound performed immediately before chest radiograph
Secondary outcome [8] 397099 0
The inter and intra observer agreement of the measurement of atelectasis in millimetres with radiological diagnosis of under-inflation on chest radiograph as defined by the presence of < 8 posterior ribs visualised at the level of the diaphragm
Timepoint [8] 397099 0
Lung ultrasound images reported twice by two investigators at least 1 month apart, blinded to clinical information.
Secondary outcome [9] 397652 0
The sensitivity of the measurement of atelectasis in millimeters with the quadrant specific CXR diagnosis of atelectasis.
Timepoint [9] 397652 0
Lung ultrasound performed immediately before chest radiograph
Secondary outcome [10] 397653 0
The correlation between the measurement of atelectasis in millimeters and severity of respiratory illness assessed by the Oxygen Saturation Index (OSI) at the time of the LUS.
Timepoint [10] 397653 0
Lung ultrasound performed immediately before chest radiograph

Eligibility
Key inclusion criteria
Very preterm infants born <32 weeks gestation and greater than 24 hours of age who require a chest radiograph
Minimum age
24 Hours
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Congenital lung malformations including congenital diaphragmatic hernia
• Major congenital cardiac defects
• Known pleural effusions or pneumothorax
• Respiratory distress syndrome where decisions about surfactant therapy are being made

Study design
Purpose
Screening
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Primary outcomes

1. To investigate whether the lung ultrasound aeration score distinguishes between the 2 groups (CXR diagnosed underinflation yes/no) a reciever operator characteristic (ROC) curve will be estimated. If the area under the ROC curve is adequate, the cut-off score for optimum sensitivity and specificity will be chosen, and sensitivity and specificity, together with 95% CIs will be estimated for this cut-off score.

Secondary outcomes
1. The linear correlation between LUS aeration score and radiological evaluation of lung inflation will be estimated.
2. For each of the 4 quadrants (right upper, right lower, left upper and left lower regions) the difference in lung aeration score between the 2 groups (CXR diagnosed underinflation yes/no), together with 95% confidence interval (CI), will be estimated. The hypothesis of no difference in mean scores will be assessed using t tests.
3. For each of the 4 quadrants (right upper, right lower, left upper and left lower regions) the kappa statistic will be used to assess the agreement between LUS diagnosis of atelectasis and radiological diagnosis of atelectasis
4. The linear correlation between LUS aeration score and Oxygen saturation indeix (OSI) will be estimated.
5. The original ultrasounds will be reported twice by two investigated (four reports in total), two reported by AS and two reported by SR, at least 1 month apart and at least 1 month post initial scan to assess intra and interobserver agreement of measurement
a. ICCs will be calculated to assess intra and interobserver agreement of continuous measurements
b. The kappa statistic will be used to assess the intra and interobserver agreement of categorical measurements

In each of the above analyses involving difference of means, if the data are assessed as skewed, the difference of medians, together with a 95% CI will be estimated using quantile regression. The hypothesis of no difference in median scores will be assessed using the p value from the quantile regression.

Recruitment
Recruitment status
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)
VIC
Recruitment hospital [1] 19864 0
The Royal Women's Hospital - Parkville
Recruitment hospital [2] 19865 0
Sunshine Hospital - St Albans
Recruitment postcode(s) [1] 34567 0
3052 - Parkville
Recruitment postcode(s) [2] 34568 0
3021 - St Albans

Funding & Sponsors
Funding source category [1] 309215 0
Government body
Name [1] 309215 0
National Health and Medical Research Council
Address [1] 309215 0
National Health and Medical Research Council
16 Marcus Clarke Street
Canberra
ACT 2601
Country [1] 309215 0
Australia
Funding source category [2] 309242 0
Hospital
Name [2] 309242 0
The Royal Women's Hospital
Address [2] 309242 0
The Royal Women's Hospital
Cnr Grattan Street & Flemington Road
Parkville
Victoria 3052
Country [2] 309242 0
Australia
Primary sponsor type
Hospital
Name
The Royal Women's Hospital
Address
The Royal Women's Hospital
Cnr Grattan Street & Flemington Road
Parkville
Victoria 3052
Country
Australia
Secondary sponsor category [1] 309751 0
None
Name [1] 309751 0
None
Address [1] 309751 0
None
Country [1] 309751 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308741 0
The Royal Children's Hospital Human Research Ethics Committee
Ethics committee address [1] 308741 0
50 Flemington Rd, Parkville VIC 3052
Ethics committee country [1] 308741 0
Australia
Date submitted for ethics approval [1] 308741 0
23/04/2021
Approval date [1] 308741 0
10/05/2021
Ethics approval number [1] 308741 0
Ethics committee name [2] 308744 0
The Royal Women's Hospital Human Research Ethics Committee
Ethics committee address [2] 308744 0
20 Flemington Rd, Parkville VIC 3052
Ethics committee country [2] 308744 0
Australia
Date submitted for ethics approval [2] 308744 0
03/03/2020
Approval date [2] 308744 0
03/06/2020
Ethics approval number [2] 308744 0

Summary
Brief summary
Preterm infants frequently require mechanical ventilation. This lifesaving intervention is associated with long term respiratory consequences, the most important being bronchopulmonary dysplasia. To minimise this risk, clinicians employ lung protective ventilation strategies. Such strategies require detailed knowledge of the lung volume state.

Lung volume is commonly assessed by chest x-rays (CXR). CXRs have disadvantages including not always being readily available, exposure to ionising radiation and only providing a static picture of lung, often at an uncertain point of the respiratory cycle.

Lung ultrasound (LUS) is being increasingly utilised in neonatal intensive care units. It has proven utility in the diagnosis of respiratory distress syndrome (RDS), pneumothorax, consolidation and the need for surfactant and mechanical ventilation.

Lung ultrasonography offers advantages over conventional imaging modalities: no ionising radiation, less manipulation of the patient and dynamic assessment of the lung. The precision and accuracy of this technique is to detect poor lung recruitment, and it’s correlation with respiratory support requirements in preterm infants warrants further exploration.

We designed a prospective observational study to explore these applications. The results of this pilot study will support further clinical studies exploring the utility of LUS in guiding neonatal respiratory support.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 111730 0
Dr Arun Sett
Address 111730 0
The Royal Women's Hospital
20 Flemington Rd, Parkville VIC 3052
Country 111730 0
Australia
Phone 111730 0
+61383453763
Fax 111730 0
Email 111730 0
Arun.Sett@thewomens.org.au
Contact person for public queries
Name 111731 0
Dr Arun Sett
Address 111731 0
The Royal Women's Hospital
20 Flemington Rd, Parkville VIC 3052
Country 111731 0
Australia
Phone 111731 0
+61383453763
Fax 111731 0
Email 111731 0
Arun.Sett@thewomens.org.au
Contact person for scientific queries
Name 111732 0
Dr Arun Sett
Address 111732 0
The Royal Women's Hospital
20 Flemington Rd, Parkville VIC 3052
Country 111732 0
Australia
Phone 111732 0
+61383453763
Fax 111732 0
Email 111732 0
Arun.Sett@thewomens.org.au

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 co-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 Arun.Sett@thewomens.org.au
What supporting documents are/will be available?
No other documents available
Summary results
No Results