ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12621001267842

Ethics application status

Approved

Date submitted

28/07/2021

Date registered

20/09/2021

Date last updated

20/02/2024

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]

None

Secondary ID [2]

Protocol number 78071

Universal Trial Number (UTN)

Trial acronym

AIROPLANE

Linked study record

Health condition

Health condition(s) or problem(s) studied:

respiratory distress

Condition category

Condition code

Reproductive Health and Childbirth

Complications of newborn

Respiratory

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 recruitment period (early 2022 - early 2024), 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]

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]

Primary outcome is the need for ongoing respiratory support at the time of leaving the delivery room. 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]

Leaving the delivery room

Secondary outcome [1]

neonatal interventions (resuscitation) required at birth, assessed by review of the patient's medical record

Timepoint [1]

hospital discharge or transfer to another hospital

Secondary outcome [2]

infant's condition at birth, as accessed by the Apgar scores documented in the patient's medical record

Timepoint [2]

5 mins of life

Secondary outcome [3]

duration of NICU/SCN admission, as assessed by review of the patient's medical record

Timepoint [3]

discharge from NICU/SCN

Secondary outcome [4]

duration of hospital admission, as assessed by the patient's medical record

Timepoint [4]

hospital discharge date

Secondary outcome [5]

admission temperature, as assessed by the patient's medical record

Timepoint [5]

admission to NICU/SCN

Secondary outcome [6]

initial blood gas analysis, as assessed by a blood gas analyser or portable i-stat device

Timepoint [6]

admission to NICU/SCN

Secondary outcome [7]

need for surfactant treatment, based on clinician discretion

Timepoint [7]

hospital discharge or transfer to another hospital

Secondary outcome [8]

diagnosis of air leak condition, as assessed by chest x-ray or clinical diagnosis

Timepoint [8]

hospital discharge or transfer to another hospital

Secondary outcome [9]

duration of mechanical ventilation, as assessed by the patient's medical record

Timepoint [9]

upon discharge from NICU/SCN

Secondary outcome [10]

duration of non-invasive respiratory support, as assessed by the patient's medical record

Timepoint [10]

upon discharge from the NICU/SCN

Secondary outcome [11]

hospital discharge or transfer to another hospital

Timepoint [11]

NICU/SCN admission

Secondary outcome [12]

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]

hospital discharge or transfer to another hospital

Secondary outcome [13]

composite outcome of diagnosis and grade of intracranial haemorrhage, as assessed by patient medical records and cranial ultrasound

Timepoint [13]

hospital discharge or transfer to another hospital

Secondary outcome [14]

use of intravenous nutrition, as assessed by the patient's medical record

Timepoint [14]

hospital discharge or transfer to another hospital

Secondary outcome [15]

use of breast milk at feeding onset and at discharge, as assessed by the patient's medical record

Timepoint [15]

hospital discharge or transfer to another hospital

Secondary outcome [16]

diagnosis and treatment of low blood glucose, as assessed by the patient's medical record and blood test results

Timepoint [16]

hospital discharge or transfer to another hospital

Secondary outcome [17]

diagnosis and treatment of jaundice, as assessed by the patient's medical record

Timepoint [17]

upon discharge from NICU/SCN

Secondary outcome [18]

death

Timepoint [18]

NICU/SCN discharge

Secondary outcome [19]

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]

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 participating Victorian hospital across the 2 year trial period (2022/2023)
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

Sex

Both males and females

Can healthy volunteers participate?

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 upon leaving the delivery room, 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

Recruiting

Date of first participant enrolment

Anticipated

30/09/2022

Actual

15/12/2022

Date of last participant enrolment

Anticipated

30/09/2024

Actual

Date of last data collection

Anticipated

30/10/2024

Actual

Sample size

Target

1200

Accrual to date

321

Final

Recruitment in Australia

Recruitment state(s)

NSW,VIC

Recruitment hospital [1]

The Royal Women's Hospital - Parkville

Recruitment hospital [2]

Monash Children’s Hospital - Clayton

Recruitment hospital [3]

Mercy Hospital for Women - Heidelberg

Recruitment hospital [4]

Sunshine Hospital - St Albans

Recruitment hospital [5]

The Northern Hospital - Epping

Recruitment hospital [6]

Casey Hospital - Berwick

Recruitment hospital [7]

Werribee Mercy Hospital - Werribee

Recruitment hospital [8]

Albury Wodonga Health - Wodonga campus - Wodonga

Recruitment hospital [9]

Box Hill Hospital - Box Hill

Recruitment hospital [10]

Ballarat Health Services (Base Hospital) - Ballarat Central

Recruitment hospital [11]

Bendigo Health Care Group - Bendigo Hospital - Bendigo

Recruitment hospital [12]

Angliss Hospital - Upper Ferntree Gully

Recruitment hospital [13]

Sandringham Hospital - Sandringham

Recruitment hospital [14]

Frances Perry House - Parkville

Recruitment hospital [15]

Epworth Freemasons (Victoria Parade) - East Melbourne

Recruitment hospital [16]

St Vincent's Private Hospital - Fitzroy

Recruitment hospital [17]

Frankston Hospital - Frankston

Recruitment hospital [18]

Goulburn Valley Health - Shepparton campus - Shepparton

Recruitment hospital [19]

Wimmera Health Care Group - Horsham - Horsham

Recruitment hospital [20]

St George Hospital - Kogarah

Recruitment hospital [21]

Wollongong Hospital - Wollongong

Recruitment hospital [22]

Royal Hospital for Women - Randwick

Recruitment hospital [23]

Blacktown Hospital - Blacktown

Recruitment hospital [24]

Campbelltown Hospital - Campbelltown

Recruitment postcode(s) [1]

3052 - Parkville

Recruitment postcode(s) [2]

3168 - Clayton

Recruitment postcode(s) [3]

3084 - Heidelberg

Recruitment postcode(s) [4]

3021 - St Albans

Recruitment postcode(s) [5]

3076 - Epping

Recruitment postcode(s) [6]

3030 - Werribee

Recruitment postcode(s) [7]

3690 - Wodonga

Recruitment postcode(s) [8]

3128 - Box Hill

Recruitment postcode(s) [9]

3350 - Ballarat Central

Recruitment postcode(s) [10]

3550 - Bendigo

Recruitment postcode(s) [11]

3156 - Upper Ferntree Gully

Recruitment postcode(s) [12]

3191 - Sandringham

Recruitment postcode(s) [13]

3002 - East Melbourne

Recruitment postcode(s) [14]

3065 - Fitzroy

Recruitment postcode(s) [15]

3199 - Frankston

Recruitment postcode(s) [16]

3630 - Shepparton

Recruitment postcode(s) [17]

3400 - Horsham

Recruitment postcode(s) [18]

2217 - Kogarah

Recruitment postcode(s) [19]

2500 - Wollongong

Recruitment postcode(s) [20]

2031 - Randwick

Recruitment postcode(s) [21]

2148 - Blacktown

Recruitment postcode(s) [22]

2560 - Campbelltown

Funding & Sponsors

Funding source category [1]

University

Name [1]

University of Melbourne

Address [1]

Swanston St
Parkville VIC 3052

Country [1]

Australia

Funding source category [2]

Other Collaborative groups

Name [2]

Centre of Research Excellence in Newborn Medicine, Murdoch Children's Research Institute

Address [2]

Flemington Rd
Parkville , Victoria 3052

Country [2]

Australia

Funding source category [3]

Government body

Name [3]

National Health and Medical Research Council

Address [3]

414 Latrobe St
Melbourne
Victoria 3000

Country [3]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Royal Children's Hospital Human Research Ethics Committee

Ethics committee address [1]

Royal Children's Hospital
50 Flemington Rd
Parkville VIC 3052

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

06/08/2021

Approval date [1]

06/04/2022

Ethics approval number [1]

HREC/78071/RCHM-2021

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 upon leaving the delivery room.
This study will be conducted as an unblinded, multi-centre, cluster randomised crossover trial, with recruitment occurring over a 2 year period, overlapping with GenV recruitment.
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

www.airoplanetrial.org.au

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

A/Prof Louise Owen

Address

Women's Newborn Research Centre
Royal Women's Hospital
20 Flemington Rd
Parkville VIC 3052

Country

Australia

Phone

+613 8345 3763

Fax

+613 8345 3789

[email protected]

Contact person for public queries

Name

A/Prof Louise Owen

Address

Women's Newborn Research Centre
Royal Women's Hospital
20 Flemington Rd
Parkville VIC 3052

Country

Australia

Phone

+613 8345 3763

Fax

+613 8345 3789

[email protected]

Contact person for scientific queries

Name

A/Prof Louise Owen

Address

Women's Newborn Research Centre
Royal Women's Hospital
20 Flemington Rd
Parkville VIC 3052

Country

Australia

Phone

+613 8345 3763

Fax

+613 8345 3789

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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

No additional documents have been identified.

Trial Review

Documents added manually

Documents added automatically