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Trial registered on ANZCTR


Registration number
ACTRN12615000380594
Ethics application status
Approved
Date submitted
3/03/2015
Date registered
27/04/2015
Date last updated
30/07/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Description of Lung Ultrasound From Initial Neonatal Transition, The DOLFIN Study
Scientific title
Capturing and evaluating lung ultrasound images, heart rate, and saturation of peripheral oxygen in term and late preterm (>32/40 weeks) infants not expected to require respiratory support at birth to determine whether ultrasound images of lungs have predictable changes in the first few hours of life.
Secondary ID [1] 286282 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neonatal resuscitation 294351 0
Lung aeration at birth 294352 0
Condition category
Condition code
Reproductive Health and Childbirth 294671 294671 0 0
Childbirth and postnatal care
Reproductive Health and Childbirth 294672 294672 0 0
Complications of newborn
Respiratory 294673 294673 0 0
Normal development and function of the respiratory system

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
This is a prospective, observational study of spontaneously breathing term and late preterm infants in the delivery room. The primary outcome will be to determine if ultrasound images of the lungs have predictable changes during the first few hours of life.

Antenatal consent will be obtained from the parents prior to enrolment after admission to birth suites and initial assessment of the obstetric team or during the final prenatal visit. Consent will only obtained if not in established labour.

Ultrasound images will be obtained using the Vividi (GE Healthcare, Wauwatosa, USA). An investigator will perform serial lung ultrasound exams, recordings 3-5 second clips of the right and left lung fields using 2D imaging and M-mode. The lung ultrasound exams will be brief. We will use a timer to limit exams to 2 minutes or less from the time of placing the ultrasound gel on the baby’s skin. Lung ultrasound exams will be performed at 6 time points: less than 10 minutes of life, 10-20 minutes of life, 1 hour of life, 2 hours of life, 4-6 hours of life, and 24-72 hours of life (the final exam targeting the time frame closest to discharge). If the lungs appear to have reached full aeration on two consecutive exams by the ultrasonographer (bilateral presence of A-lines with normal lung sliding), the study will be considered complete and no further images will be obtained. Prior to application to the baby’s skin, the ultrasound gel will warmed by placing it on a clean gauze under the radiant warmer in the patient’s room. After the exam, the ultrasound gel will be removed from the baby’s skin.

At the one hour exam, ultrasound images of the will be obtained from the anterior, axillary, and posterior chest of the baby. The purpose of obtaining additional images at the one hour exam will be to test if there is a difference in lung aeration and fluid clearance with the probe positioned at different areas of the chest. In a study of 154 term and late preterm babies, Raimondi and colleagues performed lung ultrasound exams at 1-2 hours of life. Nine percent, 30%, and 61% had type 1, 2, and 3 lung ultrasound findings respectively. Therefore, the one hour exam may be ideal to compare images in different sections of the chest because of the variety of lung aeration grades and less potential to interfere with maternal bonding. The information obtained from the additional images will help standardize the lung ultrasound exam. The one hour exam will be limited to 5 minutes.

Lung ultrasound clips will be independently collected by an investigator (DB). 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 (LF, OK, SR). The degree of lung aeration will be assigned based on the grade of these images at type 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 will test inter-rater reliability of characterizing lung ultrasound images as type 1, 2, or 3 by having the three blinded ultra-sonographers independently evaluate each ultrasound clip using a Spearman’s rank-order test.

Before the ultrasound exams, we will place a pulse oximetry sensor on the baby’s right hand or wrist to measure the baby’s heart rate and oxygen levels. These measurements can be obtained while the baby is on the mother’s chest or being held by the family. Heart rate and SpO2 will be obtained using either an NM3 Respiratory Profile Monitor (Philips Respironics, The Netherlands) or Radical 7 pulse oximeter (Masimo, California, USA). The heart rate, and SpO2 will be converted from analog to digital signal for statistical analysis. Measurements recorded will be analyzed using Stata Software (StataCorp, College Station, Texas, USA) for statistical analysis. The pulse oximeter will be applied to the baby’s right hand or wrist at each prior to each of the ultrasound examinations and be removed after the ultrasound exam is finished. If available, we will also record the umbilical arterial cord blood gas for analysis.

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

Our goal is obtain the desired data without altering the experience of the parents as they introduce a new member to their family and to avoid any interference with the clinicians caring for the baby. The lung ultrasound exams may be performed on the warming bed with the agreement of the clinician caring for the baby. If the clinical team decides that the baby is well enough to be moved from the warming bed to be with the mother, lung ultrasound exams can also with the infant on the mother’s chest or while being held by a family member. If the baby cannot be held by the mother (or other family member) but the baby can be positioned close to the mother, there will be a dedicated research trolley with a warming mattress available to place the baby as close as possible to the mother for lung ultrasound exams. The natural transition of the healthy newborn includes bonding with the mother after birth. The study should not preclude skin to skin contact of babies or breastfeeding with their mothers in the first ten minutes of life.

We will review the data collected after enrolling 10 and 50 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.

The research team has over 10 years of experience studying neonatal transition in the delivery room The measurements obtained from this cohort of babies constitutes an observational study. This data will provide valuable information on the appearance of the lungs on ultrasound from birth through the first day of life and may serve as crucial baseline data for future interventional studies intended to improve respiratory care of newborns.

The measurements and images obtained from this cohort of babies constitutes an observational study. The data will provide valuable information on lung ultrasound in the first minutes to hours after birth.
Intervention code [1] 291307 0
Not applicable
Comparator / control treatment
Nil
Control group
Uncontrolled

Outcomes
Primary outcome [1] 294425 0
The primary outcome will be to determine if ultrasound images of the lungs have predictable changes during the first few hours of life. Ultrasound images will be obtained using the Vividi (GE Healthcare, Wauwatosa, USA).
Timepoint [1] 294425 0
We will use a timer to limit exams to 2 minutes or less from the time of placing the ultrasound gel on the baby’s skin. Lung ultrasound exams will be performed at 6 time points: less than 10 minutes of life, 10-20 minutes of life, 1 hour of life, 2 hours of life, 4-6 hours of life, and 24-72 hours of life (the final exam targeting the time frame closest to discharge). If the lungs appear to have reached full aeration on two consecutive exams by the ultrasonographer (bilateral presence of A-lines with normal lung sliding), the study will be considered complete and no further images will be obtained.
Secondary outcome [1] 313278 0
To determine the proportion of babies with aerated lungs at designated time points listed in the research plan. Ultrasound images will be obtained using the Vividi (GE Healthcare, Wauwatosa, USA).
Timepoint [1] 313278 0
We will use a timer to limit exams to 2 minutes or less from the time of placing the ultrasound gel on the baby’s skin. Lung ultrasound exams will be performed at 6 time points: less than 10 minutes of life, 10-20 minutes of life, 1 hour of life, 2 hours of life, 4-6 hours of life, and 24-72 hours of life (the final exam targeting the time frame closest to discharge). If the lungs appear to have reached full aeration on two consecutive exams by the ultrasonographer (bilateral presence of A-lines with normal lung sliding), the study will be considered complete and no further images will be obtained.
Secondary outcome [2] 313279 0
To determine the average time to a fully aerated lung based on ultrasound imaging. Ultrasound images will be obtained using the Vividi (GE Healthcare, Wauwatosa, USA).
Timepoint [2] 313279 0
We will use a timer to limit exams to 2 minutes or less from the time of placing the ultrasound gel on the baby’s skin. Lung ultrasound exams will be performed at 6 time points: less than 10 minutes of life, 10-20 minutes of life, 1 hour of life, 2 hours of life, 4-6 hours of life, and 24-72 hours of life (the final exam targeting the time frame closest to discharge). If the lungs appear to have reached full aeration on two consecutive exams by the ultrasonographer (bilateral presence of A-lines with normal lung sliding), the study will be considered complete and no further images will be obtained.
Secondary outcome [3] 313280 0
To correlate the degree of lung aeration with the heart rate (HR) and saturation of peripheral oxygen (SpO2). Ultrasound images will be obtained using the Vividi (GE Healthcare, Wauwatosa, USA). HR and SpO2 will be obtained using an NM3 Respiratory Function Monitor (Philips, California USA) or a Radical-7 Pulse Oximeter (California, USA).
Timepoint [3] 313280 0
We will use a timer to limit exams to 2 minutes or less from the time of placing the ultrasound gel on the baby’s skin. Lung ultrasound exams will be performed at 6 time points: less than 10 minutes of life, 10-20 minutes of life, 1 hour of life, 2 hours of life, 4-6 hours of life, and 24-72 hours of life (the final exam targeting the time frame closest to discharge). If the lungs appear to have reached full aeration on two consecutive exams by the ultrasonographer (bilateral presence of A-lines with normal lung sliding), the study will be considered complete and no further images will be obtained. Prior to each lung ultrasound exam, we will place a pulse oximetry sensor on the baby's right wrist, then remove the sensor once the exam is completed.
Secondary outcome [4] 313281 0
To determine the time needed to perform a lung ultrasound exam that yields clean images easily reviewed by blinded expert sonographers. Ultrasound images will be obtained using the Vividi (GE Healthcare, Wauwatosa, USA).
Timepoint [4] 313281 0
We will use a timer to limit exams to 2 minutes or less from the time of placing the ultrasound gel on the baby’s skin. Lung ultrasound exams will be performed at 6 time points: less than 10 minutes of life, 10-20 minutes of life, 1 hour of life, 2 hours of life, 4-6 hours of life, and 24-72 hours of life (the final exam targeting the time frame closest to discharge). If the lungs appear to have reached full aeration on two consecutive exams by the ultrasonographer (bilateral presence of A-lines with normal lung sliding), the study will be considered complete and no further images will be obtained.
Secondary outcome [5] 313282 0
To document abnormalities of lung pathology using ultrasound. Ultrasound images will be obtained using the Vividi (GE Healthcare, Wauwatosa, USA).
Timepoint [5] 313282 0
We will use a timer to limit exams to 2 minutes or less from the time of placing the ultrasound gel on the baby’s skin. Lung ultrasound exams will be performed at 6 time points: less than 10 minutes of life, 10-20 minutes of life, 1 hour of life, 2 hours of life, 4-6 hours of life, and 24-72 hours of life (the final exam targeting the time frame closest to discharge). If the lungs appear to have reached full aeration on two consecutive exams by the ultrasonographer (bilateral presence of A-lines with normal lung sliding), the study will be considered complete and no further images will be obtained.

Eligibility
Key inclusion criteria
All inborn infants greater or equal to 33/40 weeks gestation, who are not expected to require respiratory support at birth, are eligible for this study. Antenatal consent from the parents will be required for enrolment.
Minimum age
No limit
Maximum age
0 Hours
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Infants will be excluded from analysis if they have a congenital abnormality. Infants will be excluded if their parents decline to give consent to this study. If there are signs of respiratory compromise or distress after birth, data collection will be delayed and ventilatory support given according to the Australian Neonatal Resuscitation guidelines. Infants who receive respiratory support for a brief period of time may still be eligible with the agreement of the clinician in charge of the infant’s care.

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Convenience sample
Timing
Prospective
Statistical methods / analysis
We plan to recruit a convenience sample of 100+ infants, born at >34 weeks gestational age. We will enrol 50 born via elective c-section and 50 born vaginally. A third group of infants to be included will be infants born via unplanned c-section after a trial of labour. We have no target size for this 3rd group. We believe that serial lung ultrasound on 100+ term and late preterm babies will be an adequate sample size to perform basic statistical evaluations, like repeated measured ANOVAs, with a chance of a type 1 error <0.05 and a power of 80%. The sample size is also adequate to test intra-relater reliability and inter-relater reliability.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
4/03/2015
Actual
4/03/2015
Date of last participant enrolment
Anticipated
3/03/2016
Actual
10/02/2016
Date of last data collection
Anticipated
Actual
28/02/2016
Sample size
Target
114
Accrual to date
Final
114
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 3527 0
The Royal Women's Hospital - Parkville
Recruitment postcode(s) [1] 9291 0
3052 - Parkville

Funding & Sponsors
Funding source category [1] 290840 0
Government body
Name [1] 290840 0
National Health and Medical Research Council Program Grant
Country [1] 290840 0
Australia
Funding source category [2] 290841 0
Hospital
Name [2] 290841 0
The Royal Women's Hospital
Country [2] 290841 0
Australia
Primary sponsor type
Individual
Name
Prof Peter Davis
Address
The Royal Women's Hospital
Locked Bag 300
Cnr of Grattan Street and Flemington Road
Parkville, VIC 3052
Country
Australia
Secondary sponsor category [1] 289529 0
Individual
Name [1] 289529 0
Prof Stuart Hooper
Address [1] 289529 0
The Ritchie Centre
MIMR-PHI Institute of Medical Research
27-31 Wright Street
Clayton, VIC 3168
Country [1] 289529 0
Australia
Other collaborator category [1] 278370 0
Individual
Name [1] 278370 0
Dr Omar Kamlin
Address [1] 278370 0
The Royal Women's Hospital
Locked Bag 300
Cnr of Grattan Street and Flemington Road
Parkville, VIC 3052
Country [1] 278370 0
Australia
Other collaborator category [2] 278371 0
Individual
Name [2] 278371 0
Dr Lisa Fox
Address [2] 278371 0
The Royal Women's Hospital
Locked Bag 300
Cnr of Grattan Street and Flemington Road
Parkville, VIC 3052
Country [2] 278371 0
Australia
Other collaborator category [3] 278372 0
Individual
Name [3] 278372 0
Dr Sheryle Rogerson
Address [3] 278372 0
The Royal Women's Hospital
Locked Bag 300
Cnr of Grattan Street and Flemington Road
Parkville, VIC 3052
Country [3] 278372 0
Australia
Other collaborator category [4] 278375 0
Individual
Name [4] 278375 0
Dr Graeme Polglase
Address [4] 278375 0
The Ritchie Centre
MIMR-PHI Institute of Medical Research
27-31 Wright Street
Clayton, VIC 3168
Country [4] 278375 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292461 0
The Royal Women's Hospital Research and Human Research Ethics Committees
Ethics committee address [1] 292461 0
Ethics committee country [1] 292461 0
Australia
Date submitted for ethics approval [1] 292461 0
07/01/2015
Approval date [1] 292461 0
27/02/2015
Ethics approval number [1] 292461 0
15/01

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 330 330 0 0
/AnzctrAttachments/368087-DOLFIN Study Protocol V4 26.02.2015.doc
Attachments [2] 331 331 0 0
/AnzctrAttachments/368087-DOLFIN Study Consent V4 26.02.2015.doc
Attachments [3] 332 332 0 0
/AnzctrAttachments/368087-DOLFIN Study Patient Data Form V4 26.02.2015.doc.docx

Contacts
Principal investigator
Name 55406 0
Dr Douglas Blank
Address 55406 0
The Royal Women's Hospital
Locked Bag 300
Cnr of Grattan Street and Flemington Road
Parkville, VIC 3052
Country 55406 0
Australia
Phone 55406 0
+61422305487
Fax 55406 0
Email 55406 0
[email protected]
Contact person for public queries
Name 55407 0
Douglas Blank
Address 55407 0
The Royal Women's Hospital
Locked Bag 300
Cnr of Grattan Street and Flemington Road
Parkville, VIC 3052
Country 55407 0
Australia
Phone 55407 0
+61422305487
Fax 55407 0
Email 55407 0
[email protected]
Contact person for scientific queries
Name 55408 0
Douglas Blank
Address 55408 0
The Royal Women's Hospital
Locked Bag 300
Cnr of Grattan Street and Flemington Road
Parkville, VIC 3052
Country 55408 0
Australia
Phone 55408 0
+61422305487
Fax 55408 0
Email 55408 0
[email protected]

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
EmbaseLung ultrasound during the initiation of breathing in healthy term and late preterm infants immediately after birth, a prospective, observational study.2017https://dx.doi.org/10.1016/j.resuscitation.2017.02.017
EmbaseLung ultrasound immediately after birth to describe normal neonatal transition: An observational study.2018https://dx.doi.org/10.1136/archdischild-2017-312818
EmbaseRespiratory changes in term infants immediately after birth.2018https://dx.doi.org/10.1016/j.resuscitation.2018.07.008
N.B. These documents automatically identified may not have been verified by the study sponsor.