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Trial registered on ANZCTR


Registration number
ACTRN12618000718246
Ethics application status
Approved
Date submitted
26/04/2018
Date registered
1/05/2018
Date last updated
4/03/2020
Date data sharing statement initially provided
2/04/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Warming and humidifying inspiratory gases to minimise lung injury during resuscitation of extremely preterm infants
Scientific title
Randomised controlled, parallel group, single centre, open label trial comparing warmed and humidified inspiratory gases to room temperature dry gases administered during resuscitation at birth in preterm babies less than or equal to 28 weeks and 6 days gestation to determine differences in lung biomarkers angiopoietin 1 and 2, and receptor for advanced glycation end products.
Secondary ID [1] 294692 0
CRF 181675
Universal Trial Number (UTN)
U1111-1212-6589
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Extreme preterm birth 307545 0
Newborn resuscitation 307549 0
Bronchopulmonary dysplasia 307550 0
Condition category
Condition code
Reproductive Health and Childbirth 306658 306658 0 0
Complications of newborn
Respiratory 306687 306687 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention is administration of warm humidified (WH) blended oxygen-air gas (approximately 37 degrees celcius and 100% relative humidity) during resuscitation. WH gas will be used for any of CPAP, mask or endotracheal ventilation administered via a standard T piece ventilator (Neopuff, Fisher and Paykel Health Care, Auckland New Zealand). WH gas will be administered to babies born vaginally or by caesarean section.

All other clinical care during resuscitation is at the discretion of the neonatal clinical team guided by a senior neonatal clinician and informed by standardised in house protocols based on ILCOR resuscitation guidelines. The resuscitating team will personalise the extent of respiratory support required (CPAP, face mask or endotracheal ventilation, level of inspired oxygen) using clinical judgement based on the clinical condition of the baby.

WH gas is administered from birth until admission to the Neonatal Unit. Following admission to the Neonatal Unit, all babies in intervention and control groups who require continuing respiratory support will receive WH gases as normal standard of care.

The heated humidified circuits used for resuscitation with WH gases will use components standardly used in intensive care (MR850 baseplate, MR290 humidifier chamber, and 900RD110 heated circuit, all components made by Fisher and Paykel Health Care, Auckland, New Zealand). Default factory settings produce a gas temperature of 39 degrees celcius close to the end of the inspiratory tubing. A short length of extension tubing is a bridge between the heated tubing and the connection to a Neopuff T piece. The humidifier chamber is filled with 30mL of water. Heated humidified circuits will be set-up and available in the birthing suite and theatres, and will be turned on when a birth is imminent and for at least 10 minutes before birth.

Blood samples (200 microlitres of whole blood) will be taken from the umbilical cord (artery), and from the baby at 12 hours, 24 hours and 48 hours after birth via an arterial line (preferred) or heel prick if there is no arterial line. Whole blood will be centrifuged immediately, plasma decanted and then frozen at -80 degrees celcius for batched analysis of biomarkers at the conclusion of the study using enzyme linked immunosorbent assays (R&D Bioscience).

Trial fidelity will be assessed by the attendance of one of the trial investigators at each delivery who will not be involved in the resuscitation but with the role of recording and timing resuscitation interventions and trial adherence. Fidelity of sample processing will similarly be via attendance of a trial investigator with sole responsibility for the samples. All clinical and sample processing variables will be recorded.
Intervention code [1] 301014 0
Prevention
Comparator / control treatment
The control treatment is administration of room temperature dry (RD) gases via a standard Neopuff set-up. Clinical care, blood sampling and biomarker analysis are otherwise the same as for the intervention group.
Control group
Active

Outcomes
Primary outcome [1] 305662 0
Plasma levels of angiopoietin 1
Timepoint [1] 305662 0
Cord blood (birth), at 12 hours, 24 hours and 48 hours after birth.
Primary outcome [2] 305663 0
Plasma levels of angiopoietin 2
Timepoint [2] 305663 0
Cord blood (birth), at 12 hours, 24 hours and 48 hours after birth
Primary outcome [3] 305689 0
Plasma levels of receptor for advanced glycation end products (RAGE)
Timepoint [3] 305689 0
Cord blood (birth), at 12 hours, 24 hours and 48 hours after birth
Secondary outcome [1] 346098 0
Plasma levels of VEGF may be measured depending on blood volumes available.
Timepoint [1] 346098 0
Cord blood (birth), at 12 hours, 24 hours and 48 hours after birth
Secondary outcome [2] 346099 0
Rectal temperature using a digital thermometer
Timepoint [2] 346099 0
On time of admission to NICU.
Secondary outcome [3] 346100 0
Chronic lung disease (bronchopulmonary dysplasia) as defined by ANZNN as continued need for any form of respiratory support (supplemental oxygen and/or assisted ventilation) at 36 weeks post menstrual age, and utilising the modified Walsh oxygen reduction air trial.
Timepoint [3] 346100 0
36 weeks + 0 days post conception
Secondary outcome [4] 346188 0
Plasma levels of inflammatory biomarkers depending on blood volumes available (exploratory outcome).
Timepoint [4] 346188 0
Cord blood (birth), at 12 hours, 24 hours and 48 hours after birth

Eligibility
Key inclusion criteria
Liveborn babies inborn at Flinders Medical Centre with birth gestation less than or equal to 28 weeks and 6 days
Minimum age
0 Hours
Maximum age
0 Hours
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Urgent or rapid delivery where there is inadequate time to prepare the delivery room with warmed humidified gases.
2. Major congenital abnormality identified before birth.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Concealment of allocation will be ensured via use of sequentially numbered sealed opaque envelopes stored securely in the Neonatal Unit. The clinical team attending the birth will open the sequentially labelled envelopes to assign treatments.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated random permuted blocks (size 2 and 4) with a 1:1 allocation, and two gestation strata: 1. Gestation 23, 24 and 25 weeks, and 2. Gestation 26, 27 and 28 weeks. The randomisation sequence will be independently prepared using Stata software.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
The target for enrolment is N=15 per group. N=15 per group will provide 80% power to detect an effect size of 1.1 for a difference between two independent groups with an alpha level=0.05. N=5 per group will be sufficient to detect an effect size of 2.0 with 80% power. Power will also be increased for endpoints with repeat measures. N=5 per group will provide 80% power for an effect size of 1.1 with 3 measures and a correlation of r=0.6 across time-points.

Comparisons will be made in the differences in biomarkers between babies receiving RD and WH gases at each time point (cord blood, 12, 24 and 48 hours), as well as differences in the change in these molecules over time. Statistical analysis will utilise mixed effects regression modelling with adjustments for multiple comparisons.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
7/05/2018
Actual
11/05/2018
Date of last participant enrolment
Anticipated
4/02/2020
Actual
15/10/2019
Date of last data collection
Anticipated
28/05/2020
Actual
16/02/2020
Sample size
Target
30
Accrual to date
Final
30
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 10798 0
Flinders Medical Centre - Bedford Park
Recruitment postcode(s) [1] 22538 0
5042 - Bedford Park

Funding & Sponsors
Funding source category [1] 299299 0
Charities/Societies/Foundations
Name [1] 299299 0
Channel 7 Children's Research Fund
Country [1] 299299 0
Australia
Primary sponsor type
University
Name
Flinders University
Address
GPO Box 2100
Adelaide
South Australia
5001
Country
Australia
Secondary sponsor category [1] 298566 0
None
Name [1] 298566 0
Address [1] 298566 0
Country [1] 298566 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300210 0
Southern Adelaide Clinical Human Research Ethics Committee
Ethics committee address [1] 300210 0
Ethics committee country [1] 300210 0
Australia
Date submitted for ethics approval [1] 300210 0
21/11/2017
Approval date [1] 300210 0
15/03/2018
Ethics approval number [1] 300210 0
312.17

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

Contacts
Principal investigator
Name 82922 0
Dr Scott Morris
Address 82922 0
College of Medicine and Public Health
Flinders University
GPO Box 2100
Adelaide
South Australia
5001
Country 82922 0
Australia
Phone 82922 0
+61 8 82044595
Fax 82922 0
+61 8 82043143
Email 82922 0
scott.morris@sa.gov.au
Contact person for public queries
Name 82923 0
Ray Farley
Address 82923 0
Neonatal Unit
Flinders Medical Centre
Flinders Drive
Bedford Park
South Australia
5042
Country 82923 0
Australia
Phone 82923 0
+61 8 82044595
Fax 82923 0
+61 8 82043143
Email 82923 0
Ray.Farley@sa.gov.au
Contact person for scientific queries
Name 82924 0
Scott Morris
Address 82924 0
College of Medicine and Public Health
Flinders University
GPO Box 2100
Adelaide
South Australia
5001
Country 82924 0
Australia
Phone 82924 0
+61 8 82044595
Fax 82924 0
+61 8 82043143
Email 82924 0
scott.morris@sa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Aggregate data only will be shared to avoid identification of individuals


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
No additional documents have been identified.