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Trial registered on ANZCTR


Registration number
ACTRN12621001267842p
Ethics application status
Submitted, not yet approved
Date submitted
28/07/2021
Date registered
20/09/2021
Date last updated
20/09/2021
Date data sharing statement initially provided
20/09/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Airoplane: Air or oxygen for preterm infants; an embedded trial
Scientific title
Airoplane: Comparing the effect of 21% versus 30% oxygen for preterm infants on the need for ongoing respiratory support; an embedded trial
Secondary ID [1] 304816 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
respiratory distress 322880 0
Condition category
Condition code
Reproductive Health and Childbirth 320456 320456 0 0
Complications of newborn
Respiratory 320457 320457 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All preterm infants of 32-35 completed weeks’ gestation, born in participating Victorian hospitals during the 2 year GenV recruitment period (2021 - 2023), who require respiratory support at delivery will be eligible for inclusion.
Treatment A will be the initial use of 21% oxygen during respiratory support (via face mask or nasal prongs) in the delivery room. This treatment will be delivered by the clinician attending the birth. All other interventions will be initiated according to the Australian Resuscitation Council (ARC) / Victorian NeoResus (neoresus.org.au) protocols, and local guidelines. No change to the randomised oxygen concentration will be permitted prior to 3 minutes of life, or within 1 minute of commencement of respiratory support, whichever is later. This 1-minute requirement mitigates for the practice of delayed/deferred cord clamping which is currently the recommended practice for all babies of this gestational age (GA) across Victoria for a duration of 30-60 seconds. The very large majority of these infants will not receive respiratory support until after the umbilical cord has been cut. However, if at any stage, an infant is bradycardic with a heart rate <60 beats per minute (bpm), or requires chest compressions or intubation, supplemental oxygen should be delivered as per local resuscitation guidelines.
Beyond the 3-minute time period (or 1-minute post commencement of respiratory support, if after 3 minutes), oxygen concentration should be titrated against peripheral oxygen saturations (SpO2) measured by pulse oximetry, as recommended by the ARC/ NeoResus guidelines.
Each hospital will be randomised to use one oxygen strategy for half of the trial recruitment period, and then switch to the other strategy for the second half of the recruitment period. Hospitals will be randomly allocated to the order in which these two interventions will be assigned. Only one crossover of interventions will occur at each site.
Adherence to the intervention will be monitored by the completion of a brief survey, which clinician's can access via a QR code to be displayed near the resuscitaire.
Intervention code [1] 321183 0
Treatment: Other
Comparator / control treatment
Treatment B will be the initial use of 30% oxygen during respiratory support (via face mask or nasal prongs) in the delivery room. This treatment will be delivered by the clinician attending the birth.
All other interventions will be initiated according to the Australian Resuscitation Council (ARC) / Victorian NeoResus (neoresus.org.au) protocols, and local guidelines. No change to the randomised oxygen concentration will be permitted prior to 3 minutes of life, or within 1 minute of commencement of respiratory support, whichever is later.
However, if at any stage, an infant is bradycardic with a heart rate <60 beats per minute (bpm), or requires chest compressions or intubation, supplemental oxygen should be delivered as per local resuscitation guidelines.
Beyond the 3-minute time period (or 1-minute post commencement of respiratory support, if after 3 minutes), oxygen concentration should be titrated against peripheral oxygen saturations (SpO2) measured by pulse oximetry, as recommended by the ARC/ NeoResus guidelines.
Control group
Active

Outcomes
Primary outcome [1] 328293 0
Primary outcome is the need for ongoing respiratory support on admission to the newborn nursery, (either a neonatal intensive care unit (NICU), or a special care nursery (SCN)). Ongoing respiratory support will include the need for intubation and mechanical ventilation, or the use of non-invasive respiratory supports such as continuous positive airway pressure (CPAP) or nasal high flow therapy (nHF), including any requirement for surfactant therapy.
This data will be collected via review of the patient's medical record.
Timepoint [1] 328293 0
Admission to NICU or SCN
Secondary outcome [1] 398386 0
neonatal interventions (resuscitation) required at birth, assessed by review of the patient's medical record
Timepoint [1] 398386 0
admission to NICU or SCN
Secondary outcome [2] 398387 0
infant's condition at birth, as accessed by the Apgar scores documented in the patient's medical record
Timepoint [2] 398387 0
5 mins of life
Secondary outcome [3] 398388 0
duration of NICU/SCN admission, as assessed by review of the patient's medical record
Timepoint [3] 398388 0
discharge from NICU/SCN
Secondary outcome [4] 398389 0
duration of hospital admission, as assessed by the patient's medical record
Timepoint [4] 398389 0
hospital discharge date
Secondary outcome [5] 398390 0
admission temperature, as assessed by the patient's medical record
Timepoint [5] 398390 0
admission to NICU/SCN
Secondary outcome [6] 398391 0
initial blood gas analysis, as assessed by a blood gas analyser or portable i-stat device
Timepoint [6] 398391 0
admission to NICU/SCN
Secondary outcome [7] 398393 0
need for surfactant treatment, based on clinician discretion
Timepoint [7] 398393 0
NICU/SCN admission
Secondary outcome [8] 398394 0
diagnosis of air leak condition, as assessed by chest x-ray or clinical diagnosis
Timepoint [8] 398394 0
NICU/SCN admission
Secondary outcome [9] 398395 0
duration of mechanical ventilation, as assessed by the patient's medical record
Timepoint [9] 398395 0
upon discharge from NICU/SCN
Secondary outcome [10] 398396 0
duration of non-invasive respiratory support, as assessed by the patient's medical record
Timepoint [10] 398396 0
upon discharge from the NICU/SCN
Secondary outcome [11] 398397 0
composite secondary outcome of diagnosis and treatment of infection, including method and duration of treatment, as assessed by the patient's medical record and blood test results, including blood cultures
Timepoint [11] 398397 0
NICU/SCN admission
Secondary outcome [12] 398398 0
composite secondary outcome of diagnosis and method treatment of patent ductus arteriosus, as assessed by patient medical records and echocardiogram findings, including outcome of any treatment as assessed by either patient medical records and/or echocardiogram findings
Timepoint [12] 398398 0
NICU/SCN admission
Secondary outcome [13] 398399 0
composite outcome of diagnosis and grade of intracranial haemorrhage, as assessed by patient medical records and cranial ultrasound
Timepoint [13] 398399 0
NICU/SCN admission
Secondary outcome [14] 398400 0
use of intravenous nutrition, as assessed by the patient's medical record
Timepoint [14] 398400 0
NICU/SCN admission
Secondary outcome [15] 398401 0
use of breast milk at feeding onset and at discharge, as assessed by the patient's medical record
Timepoint [15] 398401 0
NICU/SCN admission and at discharge
Secondary outcome [16] 398402 0
diagnosis and treatment of low blood glucose, as assessed by the patient's medical record and blood test results
Timepoint [16] 398402 0
NICU/SCN admission
Secondary outcome [17] 398403 0
diagnosis and treatment of jaundice, as assessed by the patient's medical record
Timepoint [17] 398403 0
upon discharge from NICU/SCN
Secondary outcome [18] 398404 0
death
Timepoint [18] 398404 0
NICU/SCN discharge
Secondary outcome [19] 398989 0
economic evaluation, which will access cost of hospital care and transfer, as accessed by the patient's medical record. Data will be collected by the GenV administrative hospital costing data linkage collection process for analysis. Data required will include hospital inpatient cost for the initial admission where the oxygen therapy was commenced hospital inpatient cost during the first year of life
Timepoint [19] 398989 0
NICU/SCN discharge

Eligibility
Key inclusion criteria
Each infant must meet all of the follwing to be included in the study:
o born in a Victorian hospital that is participating in GenV during the planned 2021-2023 recruitment period and consent to GenV SCN data collection
o born between at 32+0 and 35+6 weeks of gestation
o receive respiratory support in the delivery room to support transition, respiratory support includes any facemask support, such as for the provision of CPAP, intermittent positive pressure ventilation, intubation, or any combination of these interventions.
Minimum age
32 Weeks
Maximum age
35 Weeks
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Infants will be excluded if they:
o are born outside the criteria above, including those who do not receive respiratory support during transition
o have any known major congenital cardiorespiratory or craniofacial anomaly likely to affect transition, or
o a prior decision has been made not to provide intensive care (i.e. comfort care),

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Hospitals will be cluster randomised. For half of the study recruitment period at each hospital that hospital will be assigned to use Treatment A for all stabilisations in the delivery room for all infants born between 32+0 and 35+6 weeks’ GA. For the remaining half of the recruitment period hospitals will be assigned to use Treatment B for stabilisation of these infants, or vice versa.
Hospitals will be randomly allocated to the order in which these two interventions will be assigned. Only one crossover of interventions will occur at each site.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Local data from the Royal Women’s Hospital (RWH) demonstrate that of infants born 32-35+6 weeks’ GA between 2015-2020 who received respiratory support in the delivery room, and therefore would meet eligibility criteria for AIROPLANE, 51.1% (419/802) received ongoing respiratory support in the NICU (either mechanical ventilation or non-invasive support, or both).
The sample size calculation takes into consideration the total number of sites recruiting to the trial, and the number of crossover periods within the total recruitment period (n=2). Total study sites will be at least 20, with two planned intervention periods, i.e. one crossover, each study site will have one period of Treatment A (21% oxygen) and one period of Treatment B (30% oxygen), randomly assigned.
There are 34 public maternity hospitals in Victoria that manage births below 36 weeks’ gestation, and a further 15 private maternity hospitals. We intend to recruit infants at the 16 largest sites where >60 infants in the GA range 32-35 weeks GA are born annually, plus in at least 4 of the smaller centres.
To be able to find an absolute reduction in the need for ongoing respiratory support from 51% to 43%, a reduction of 8% (relative reduction ~15%) with 80% power and 5% alpha level, with 20 study sites and 2 intervention periods, we will need on average 30 infants per site, or approximately 1200 infants in total. We assume no loss to follow-up, since the primary outcome is collected prior to hospital discharge.
However, to be able to see an absolute reduction in the need for ongoing respiratory support from 51% to 46%, a reduction of 5% (relative reduction ~10%) with 90% power and 5% alpha level, with 20 study sites and 2 crossover periods, we will need approximately 4000 infants (on average 100 per site at 20 sites). Therefore, we will consider the AIROPLANE trial to be a pilot study prior to a large-scale interstate/international trial that will answer the study aims with higher power and more accuracy: The AIROSPACE trial (Air or Oxygen Support for Preterm infants: A Comparison of Effectiveness).
The primary outcome is the need for ongoing respiratory support on admission to the newborn nursery, measured as a binary variable. The incidence of the primary outcome will be summarised as the number and percentage in each treatment. The treatments will be compared using a risk difference and 95% confidence interval (CI). This is a cluster randomised cross-over trial, with a cross-sectional sample in each period and will be modelled with a generalised linear model (GLM) with an identity link function and a binomial distribution using an exchangeable correlation structure to model the correlation within each cluster, adjusted for treatment period due to the cross-over nature.
Primary analyses will be by intention-to-treat.
Dichotomous secondary outcomes will be analysed in the same manner as the primary outcomes. Continuous secondary outcomes will be analysed with similar models, using a Gaussian distribution rather than a binomial distribution. Comparisons between the trial arms will be summarised via mean differences and 95% confidence intervals of the mean differences.
Patient and hospital subgroup analyses will be performed to assess uncertainties.
If one treatment strategy were clinically superior than the other, a cost-effectiveness analysis will be conducted. Hospital data required for health economic analysis will be collected by the GenV administrative hospital costing data linkage collection process for analysis, including cost of inpatient admission in the nursery, as well as the cost of inpatient admissions in the first year of life.
There will be a safety review at 50% recruitment.

Recruitment
Recruitment status
Not yet 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] 19998 0
The Royal Women's Hospital - Parkville
Recruitment hospital [2] 20006 0
Monash Children’s Hospital - Clayton
Recruitment hospital [3] 20007 0
Mercy Hospital for Women - Heidelberg
Recruitment hospital [4] 20008 0
Sunshine Hospital - St Albans
Recruitment hospital [5] 20009 0
The Northern Hospital - Epping
Recruitment hospital [6] 20011 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment hospital [7] 20012 0
Casey Hospital - Berwick
Recruitment hospital [8] 20013 0
Werribee Mercy Hospital - Werribee
Recruitment hospital [9] 20014 0
Albury Wodonga Health - Wodonga campus - Wodonga
Recruitment hospital [10] 20015 0
Box Hill Hospital - Box Hill
Recruitment hospital [11] 20016 0
Ballarat Health Services (Base Hospital) - Ballarat Central
Recruitment hospital [12] 20017 0
Bendigo Health Care Group - Bendigo Hospital - Bendigo
Recruitment hospital [13] 20018 0
Central Gippsland Health Service (Sale) - Sale
Recruitment hospital [14] 20019 0
Angliss Hospital - Upper Ferntree Gully
Recruitment hospital [15] 20020 0
Sandringham Hospital - Sandringham
Recruitment hospital [16] 20021 0
Frances Perry House - Parkville
Recruitment hospital [17] 20022 0
Epworth Freemasons (Victoria Parade) - East Melbourne
Recruitment hospital [18] 20023 0
St Vincent's Private Hospital - Fitzroy
Recruitment hospital [19] 20024 0
Frankston Hospital - Frankston
Recruitment hospital [20] 20025 0
Goulburn Valley Health - Shepparton campus - Shepparton
Recruitment hospital [21] 20026 0
Latrobe Regional Hospital - Traralgon
Recruitment postcode(s) [1] 34706 0
3052 - Parkville
Recruitment postcode(s) [2] 34715 0
3168 - Clayton
Recruitment postcode(s) [3] 34716 0
3084 - Heidelberg
Recruitment postcode(s) [4] 34717 0
3021 - St Albans
Recruitment postcode(s) [5] 34718 0
3076 - Epping
Recruitment postcode(s) [6] 34720 0
3220 - Geelong
Recruitment postcode(s) [7] 34721 0
3806 - Berwick
Recruitment postcode(s) [8] 34722 0
3030 - Werribee
Recruitment postcode(s) [9] 34723 0
3690 - Wodonga
Recruitment postcode(s) [10] 34724 0
3128 - Box Hill
Recruitment postcode(s) [11] 34725 0
3350 - Ballarat Central
Recruitment postcode(s) [12] 34726 0
3550 - Bendigo
Recruitment postcode(s) [13] 34727 0
3850 - Sale
Recruitment postcode(s) [14] 34728 0
3156 - Upper Ferntree Gully
Recruitment postcode(s) [15] 34729 0
3191 - Sandringham
Recruitment postcode(s) [16] 34730 0
3002 - East Melbourne
Recruitment postcode(s) [17] 34731 0
3065 - Fitzroy
Recruitment postcode(s) [18] 34732 0
3199 - Frankston
Recruitment postcode(s) [19] 34733 0
3630 - Shepparton
Recruitment postcode(s) [20] 34734 0
3844 - Traralgon

Funding & Sponsors
Funding source category [1] 309186 0
University
Name [1] 309186 0
University of Melbourne
Address [1] 309186 0
Swanston St
Parkville VIC 3052
Country [1] 309186 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Murdoch Children's Research Institute
Address
Royal Children's Hospital
50 Flemington Rd
Parkville VIC 3052
Country
Australia
Secondary sponsor category [1] 310147 0
None
Name [1] 310147 0
Address [1] 310147 0
Country [1] 310147 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 309043 0
Royal Children's Hospital Human Research Ethics Committee
Ethics committee address [1] 309043 0
Royal Children's Hospital
50 Flemington Rd
Parkville VIC 3052
Ethics committee country [1] 309043 0
Australia
Date submitted for ethics approval [1] 309043 0
06/08/2021
Approval date [1] 309043 0
Ethics approval number [1] 309043 0

Summary
Brief summary
The AIROPLANE trial aims to evaluate the effect of commencing respiratory support at birth, in preterm infants born 32 to 35 completed weeks’ gestation, with either 30% or 21% oxygen.
The primary outcome is the need for ongoing respiratory support on admission to the newborn nursery, (either a neonatal intensive care unit (NICU), or a special care nursery (SCN)).
This study will be conducted as an unblinded, multi-centre, cluster randomised crossover trial, with recruitment occurring over the 2 year period coinciding with GenV.
We hypothesise that if respiratory support is required during transition at birth, commencing with 30% oxygen will be superior to commencing with 21% oxygen, resulting in improved transition and less need for ongoing respiratory support.

Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 112762 0
A/Prof Louise Owen
Address 112762 0
Women's Newborn Research Centre
Royal Women's Hospital
20 Flemington Rd
Parkville VIC 3052
Country 112762 0
Australia
Phone 112762 0
+613 8345 3763
Fax 112762 0
+613 8345 3789
Email 112762 0
louise.owen@thewomens.org.au
Contact person for public queries
Name 112763 0
A/Prof Louise Owen
Address 112763 0
Women's Newborn Research Centre
Royal Women's Hospital
20 Flemington Rd
Parkville VIC 3052
Country 112763 0
Australia
Phone 112763 0
+613 8345 3763
Fax 112763 0
+613 8345 3789
Email 112763 0
louise.owen@thewomens.org.au
Contact person for scientific queries
Name 112764 0
A/Prof Louise Owen
Address 112764 0
Women's Newborn Research Centre
Royal Women's Hospital
20 Flemington Rd
Parkville VIC 3052
Country 112764 0
Australia
Phone 112764 0
+613 8345 3763
Fax 112764 0
+613 8345 3789
Email 112764 0
louise.owen@thewomens.org.au

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 other documents available
Summary results
No Results