Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617001256369
Ethics application status
Approved
Date submitted
25/08/2017
Date registered
29/08/2017
Date last updated
16/04/2021
Date data sharing statement initially provided
16/04/2021
Date results provided
16/04/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
The Description of Lung Ultrasound From Initial Neonatal Transition in Very Preterm Infants
Scientific title
The Description of Lung Ultrasound From Initial Neonatal Transition in Very Preterm Infants
Secondary ID [1] 292738 0
Nil known
Universal Trial Number (UTN)
Trial acronym
The DOLFIN Jr Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prematurity
 304509 0
Respiratory distress syndrome 304510 0
Neonatal apnea 304511 0
Condition category
Condition code
Respiratory 303851 303851 0 0
Other respiratory disorders / diseases
Reproductive Health and Childbirth 303852 303852 0 0
Complications of newborn

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
This will be a single centre observational study at the Royal Women’s Hospital. We plan to obtain serial lung ultrasound images in premature infants less than 29 weeks starting with in the delivery room through the first 48 hours after birth so that we can describe the appearance of the lungs during neonatal transition. A secondary outcome is to investigate if early lung ultrasound can predict the level of respiratory support the infant will need in the first days after birth.

The primary investigator will be responsible for recruitment for this study. If the primary investigator is not available, designated, experienced co-investigators may approach the family for consent. Consent will be sought after initial assessment of the obstetric team. No woman in physical distress will be approached for consent. Families will only be approached after discussion and permission with the midwife and obstetrician responsible for the care of the expecting mother. We understand that the potential delivery of an extremely premature baby is a stressful event. We want to ensure that it is appropriate to approach the family prior to seeking consent.

Infants will be excluded if they have a congenital abnormality that affects the lungs, like congenital diaphragmatic hernia. Infants will be excluded if their parents decline to give consent to this study. We will also exclude the infants of parents who cannot speak English.

Equipment

We will obtain serial LUS images, using a GE Venue 50 (Phillips, USA) ultrasound machine and a “hockey stick,” L8-18i linear transducer with an initial depth of 2cm and a gain of 60. Images will be interpreted, graded, and recorded during or immediately after each LUS exam by the ultrasonographer. We plan to obtain 3 second lung ultrasound video clips of the right and left side of the chest between birth and 10 minutes after birth, between 10-20 minutes after birth, at 1-3 hours after birth (after being stabilized in the NICU) and at 24-48 hours after birth. Additionally, if the baby is intubated for surfactant delivery, we plan to obtain images after intubation, immediately prior to surfactant delivery and after surfactant delivery (targeting 30 minutes to 3 hours depending timing of cares and infant wellbeing) and immediately prior to the first extubation attempt as well as after extubation (targeting 30 minutes to 3 hours depending on timing with cares and infant wellbeing).

Other data will be collected from the newborn’s medical chart, included gestational age, weight, exposure to antenatal steroids, time of umbilical cord clamping, presence of maternal chorioanmionitis, APGAR scores, need for resuscitation, umbilical cord blood gases, first recorded temperature, mode of delivery, respiratory support parameters, and other short term outcome data until discharge from the hospital.

Lung Ultrasound Exam Technique

Babies will be examined in the delivery room on the warming bed or in the isolate in the NICU. We aim to minimize any potential interference with neonatal stabilization. We will ask permission from the treatment team prior to all study investigations. We will attempt to limit data collection to less than 2 minutes of direct patient contact (either touching the baby directly or with the isolate doors open) during each time point. During each exam, the LUS probe will be placed in the baby’s axillae with the notch pointed superiorly towards the baby’s head. The probe will then adjusted until a “bat sign” is achieved and the lungs appeared as aerated and dry as possible. The “bat sign” describes the appearance of white, hyperechoic pleural line dipping below the hypoechoic, black rib shadows that resembles a bat in flight. The probe we will use for image collection is 3.5cm long and a typical image included the lung parenchyma from 4-5 rib spaces in this population. We will place the LUS probe in the baby’s axillae because we feel we can obtain consistent images regardless of the baby’s position, either prone or supine, while minimizing handling which is relevant to a baby in the intensive care setting.

Lung Ultrasound Grading

The degree of lung aeration and fluid can be graded as type 0, 1, 2, or 3. Type 0 is the appearance of the lungs with a lack of air in the lung tissue (atelectasis) and has been noted in premature infants prior to intubation. This is a “true” lung ultrasound image with no air-based artifact. Type 1 represents consolidated, white-out lungs seen in RDS. Type 2, which is the presence of vertical B-lines arising from the pleural lines (“lung rockets” or “comet tails”), represents partial fluid resorption in the neonatal lung and is not associated with respiratory distress syndrome or non-invasive ventilation failure. Type 3, indicated by A-lines with the presence of lung sliding, represents an aerated, dry lung expected to be seen in healthy lungs. A-lines are artifacts created by ultrasound beams hitting air. Ultrasound beams reverberate off of the air and create a series of horizontal, hyperechoic lines that are equidistant to the distance between the skin and pleural. A-lines are also seen in pneumothorax. Healthy lung and pneumothorax can be differentiated by the presence of normal lung sliding in the healthy lung, seen as characteristic movement of the pleural line on 2-D video loops or the “seashore sign” on M-mode.

Lung ultrasound clips will be independently collected by an investigator. Two 2-D clips and 2 images captured with M-mode for each exam will be de-identified, coded, and blindly graded by 2 consultants with expertise in ultrasonography. The degree of lung aeration will be assigned based on the grade of these images at type 0, 1, 2, or 3 using a previously published grading system. In the event of a disagreement in grading, if 2/3 evaluators agree, that grade will be assigned. If all three evaluators assign a different grade, we will review the images openly in a group discussion. We will test inter-rater reliability of characterizing lung ultrasound images as type 0, 1, 2, or 3 by having the three blinded ultra-sonographers independently evaluate each ultrasound clip using a Spearman’s rank-order test.

Safety Monitoring

If the investigators observe any concerning findings on lung ultrasound (evidence of pneumothorax or effusion), they will immediately notify the clinical team caring for the baby.

We will review the data collected after enrolling 10 and 20 babies. The purpose will be to review for adverse outcomes, quality of ultrasound images, efficacy of data collection and grading. Specifically, we will monitor the baby’s first temperature collected by the clinical team, the potential of interfering with patient care, review the quality of ultrasound images using different exam techniques and settings (like location of ultrasound probe, gain, and depth), and the inter-relater reliability.
Intervention code [1] 298982 0
Diagnosis / Prognosis
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 303205 0
To characterize changes in lung ultrasound images from birth in preterm infants born at less than 29 weeks at the designated time points listed in the research plan.
Timepoint [1] 303205 0
We plan to obtain 3 second lung ultrasound video clips of the right and left side of the chest between birth and 10 minutes after birth, between 10-20 minutes after birth, at 1-3 hours after birth (after being stabilized in the NICU) and at 24-48 hours after birth. Additionally, if the baby is intubated for surfactant delivery, we plan to obtain images immediately prior to surfactant delivery and after surfactant delivery (targeting 30 minutes to 3 hours depending timing of cares and infant wellbeing) and immediately prior to the first extubation attempt as well as after extubation (targeting 30 minutes to 3 hours depending on timing with cares and infant wellbeing).
Secondary outcome [1] 338234 0
1) To observe if there are correlations between LUS images in the delivery room and the level of respiratory support provided for infants born at less than 29 weeks during the first 72 hours after birth.
Timepoint [1] 338234 0
72 hours
Secondary outcome [2] 338235 0
2) To correlate the lung ultrasound image grades with the level of respiratory support the baby is receiving (FiO2, mean airway pressure, and oxygen index when available).
Timepoint [2] 338235 0
First 72 hours after birth
Secondary outcome [3] 338236 0
4) To compare lung ultrasound images obtained in the delivery room and after admission to the NICU to Xray images when available.
Timepoint [3] 338236 0
1st 6 hours after birth
Secondary outcome [4] 338237 0
5) To document the changes in lung ultrasound before and after surfactant administration in infants born at less than 29 weeks.
Timepoint [4] 338237 0
First 24 hours after birth

Eligibility
Key inclusion criteria
Infants born at less than 32 weeks gestational age are eligible for this study. Antenatal consent from parent will be required for enrolment.
Minimum age
0 Hours
Maximum age
0 Hours
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Not applicable, all participants will be extremely premature at delivery.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Medical data on each infant will be collected on Case Report Forms. De-identified information will be collected via the Venue 50 ultrasound machine. All information will then be entered into an database for analysis (Microsoft Excel, USA and IBM SPSS, USA).

This study is an observational study and is therefore not powered for a primary outcome. The intention of this study is to gather information to generate a hypothesis for a future study. We feel that enrolling 50 babies will provide us with enough information to characterize changes in lung ultrasound images from birth in preterm infants =28 weeks. According to our hospital statistics used for antenatal consults, there was an annual average of 118 babies born at less than 29 weeks gestation at the RWH between 2003-2005. Therefore, we should be able to obtain antenatal consent and enrol 50 eligible babies over a 12 month period with an additional 6 months to collect all relevant data regarding short term outcomes from hospital records.

Lung ultrasound clips will be independently collected by an investigator. Two 2-D clips and 2 images captured with M-mode for each exam will be de-identified, coded, and blindly graded by 3 consultants with expertise in ultrasonography. The degree of lung aeration will be assigned based on the grade of these images at type 0, 1, 2, or 3 using a previously published grading system. In the event of a disagreement among the blinded consultants, if 2/3 consultants agree, that grade will be assigned. If all three consultants assign a different grade, we will review the images openly in a group discussion. We have previously tested inter-rater reliability of characterizing lung ultrasound images as type 0, 1, 2, or 3 by having three blinded ultra-sonographers independently evaluate each ultrasound clip using a Spearman’s rank-order test. The appearance of the lungs using ultrasound (type 0, 1, 2, or 3), RR, HR, and SpO2, at single time points will be described, including lung ultrasound images prior and after surfactant administration and a trial of extubation when applicable.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
4/09/2017
Actual
17/01/2018
Date of last participant enrolment
Anticipated
4/09/2018
Actual
6/12/2019
Date of last data collection
Anticipated
7/09/2018
Actual
3/03/2020
Sample size
Target
50
Accrual to date
Final
52
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 8890 0
The Royal Women's Hospital - Parkville
Recruitment hospital [2] 19109 0
Monash Children’s Hospital - Clayton
Recruitment postcode(s) [1] 17140 0
3052 - Parkville
Recruitment postcode(s) [2] 33669 0
3168 - Clayton

Funding & Sponsors
Funding source category [1] 297374 0
Government body
Name [1] 297374 0
National Health and Medical Research Council Program Grant
Country [1] 297374 0
Australia
Funding source category [2] 297378 0
Hospital
Name [2] 297378 0
The Royal Women's Hospital
Country [2] 297378 0
Australia
Primary sponsor type
Individual
Name
Dr Douglas Blank
Address
The Royal Women's Hospital
Newborn Research
Cnr Grattan Street & Flemington Road
Locked Bag 300
Parkville, VIC 3052
Country
Australia
Secondary sponsor category [1] 296352 0
Individual
Name [1] 296352 0
Prof Peter Davis
Address [1] 296352 0
The Royal Women's Hospital Newborn Research Cnr Grattan Street & Flemington Road Locked Bag 300 Parkville, VIC 3052
Country [1] 296352 0
Australia
Secondary sponsor category [2] 296358 0
Individual
Name [2] 296358 0
Dr Sheryle Rogerson
Address [2] 296358 0
The Royal Women's Hospital Cnr Grattan Street & Flemington Road Locked Bag 300 Parkville, VIC 3052
Country [2] 296358 0
Australia
Secondary sponsor category [3] 296359 0
Individual
Name [3] 296359 0
Dr Omar Kamlin
Address [3] 296359 0
The Royal Women's Hospital Cnr Grattan Street & Flemington Road Locked Bag 300 Parkville, VIC 3052
Country [3] 296359 0
Australia
Secondary sponsor category [4] 296360 0
Individual
Name [4] 296360 0
Dr Stefan Kane
Address [4] 296360 0
The Royal Women's Hospital Cnr Grattan Street & Flemington Road Locked Bag 300 Parkville, VIC 3052
Country [4] 296360 0
Australia
Secondary sponsor category [5] 296361 0
Individual
Name [5] 296361 0
Prof Stuart Hooper
Address [5] 296361 0
The Ritchie Centre, Hudson Institute of Medical Research
Monash University
27-31 Wright Street
Clayton, VIC 3168
Country [5] 296361 0
Australia
Secondary sponsor category [6] 296362 0
Individual
Name [6] 296362 0
A/Prof Graeme Polglase
Address [6] 296362 0
The Ritchie Centre, Hudson Institute of Medical Research
Monash University
27-31 Wright Street
Clayton, VIC 3168
Country [6] 296362 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298478 0
The Royal Women's Hospital Human Research and Ethics Committee
Ethics committee address [1] 298478 0
Ethics committee country [1] 298478 0
Australia
Date submitted for ethics approval [1] 298478 0
20/09/2016
Approval date [1] 298478 0
16/01/2017
Ethics approval number [1] 298478 0
16/37
Ethics committee name [2] 308322 0
Monash Health
Ethics committee address [2] 308322 0
Ethics committee country [2] 308322 0
Australia
Date submitted for ethics approval [2] 308322 0
14/11/2018
Approval date [2] 308322 0
04/03/2019
Ethics approval number [2] 308322 0
NMA HREC: HREC/48677/MonH-2018-157190(v1)

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

Contacts
Principal investigator
Name 77210 0
Dr Douglas Blank
Address 77210 0
Monash Newborn, Monash Children's Hospital
246 Clayton Road
Clayton, VIC, 3168
Country 77210 0
Australia
Phone 77210 0
+61422305487
Fax 77210 0
Email 77210 0
[email protected]
Contact person for public queries
Name 77211 0
Douglas Blank
Address 77211 0
Monash Newborn, Monash Children's Hospital
246 Clayton Road
Clayton, VIC, 3168
Country 77211 0
Australia
Phone 77211 0
+61422305487
Fax 77211 0
Email 77211 0
[email protected]
Contact person for scientific queries
Name 77212 0
Douglas Blank
Address 77212 0
Monash Newborn, Monash Children's Hospital
246 Clayton Road
Clayton, VIC, 3168
Country 77212 0
Australia
Phone 77212 0
+61422305487
Fax 77212 0
Email 77212 0
douglas.blank@monashhealth,org

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?

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
EmbaseLung ultrasound during newborn resuscitation predicts the need for surfactant therapy in very- and extremely preterm infants.2021https://dx.doi.org/10.1016/j.resuscitation.2021.01.025
N.B. These documents automatically identified may not have been verified by the study sponsor.