Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12620001086954
Ethics application status
Approved
Date submitted
14/07/2020
Date registered
20/10/2020
Date last updated
20/10/2020
Date data sharing statement initially provided
20/10/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Nasal vs face mask Continuous Positive Airway Pressure (CPAP) for neonatal resuscitation
Scientific title
Nasal versus face mask Continuous Positive Airway Pressure (CPAP) for initial respiratory support in very preterm infants, a randomized controlled trial.
Secondary ID [1] 301775 0
NA
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Premature birth at less than 32 weeks gestational age 318241 0
Neonatal resuscitation 318242 0
Respiratory distress syndrome 318243 0
Condition category
Condition code
Reproductive Health and Childbirth 316254 316254 0 0
Complications of newborn
Reproductive Health and Childbirth 316255 316255 0 0
Childbirth and postnatal care
Respiratory 317077 317077 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
In the intervention arm initial respiratory support immediately after birth is provided using a nasal mask for CPAP and supplemental oxygen. In the control arm initial respiratory support is provided using a face mask.

The duration of this support is between the time of birth and transfer to the NICU, about 10-20 minutes.

The treatment will be administered by the neonatal team, typically the neonatal registrar, fellow, nurse practitioner, or consultant, depending on the composition of the team at birth. Note, all infants born at less than 27 weeks and all twins born at less than 29 weeks will have a consultant present at the birth.

Our primary outcome is the proportion of infants that are managed with CPAP only in the nasal CPAP versus face mask CPAP groups. Failure of CPAP only treatment means that the infant received positive pressure ventilation via a facemask or an endotracheal tube. Success of the intervention will be recorded in the existing medical records.
Intervention code [1] 318071 0
Treatment: Devices
Comparator / control treatment
In the intervention arm initial respiratory support immediately after birth is provided using a nasal mask for CPAP and supplemental oxygen. In the control arm initial respiratory support is provided using a face mask.

The duration of this support is between the time of birth and transfer to the NICU, about 10-20 minutes.

The treatment will be administered by the neonatal team, typically the neonatal registrar, fellow, nurse practitioner, or consultant, depending on the composition of the team at birth. Note, all infants born at less than 27 weeks and all twins born at less than 29 weeks will have a consultant present at the birth.

Our primary outcome is the proportion of infants that are managed with CPAP only in the nasal CPAP versus face mask CPAP groups. Failure of CPAP only treatment means that the infant received positive pressure ventilation via a facemask or an endotracheal tube. Success of the intervention will be recorded in the existing medical records.
Control group
Active

Outcomes
Primary outcome [1] 324432 0
The primary outcome is the proportion of infants that are managed with CPAP only in the nasal CPAP vs face mask CPAP groups immediately after birth.

The success of the intervention is recorded in the existing medical records.
Timepoint [1] 324432 0
Prior to transport to the NICU, typically 10 minutes after birth.
Secondary outcome [1] 384626 0
Percent of infants in each group that are intubated prior to transfer to the NICU.

The success of the intervention is recorded in the existing medical records.
Timepoint [1] 384626 0
Prior to transfer to the NICU, typically 10 minutes after birth.
Secondary outcome [2] 384627 0
Maximum inflation pressure provided for initial neonatal stabilisation.

This information is recorded in the existing medical records.
Timepoint [2] 384627 0
Prior to transfer to the NICU, typically 10 minutes after birth.
Secondary outcome [3] 384628 0
Maximum FiO2 provided during initial neonatal stabilisation.

This information is recorded in the existing medical records.
Timepoint [3] 384628 0
Prior to transfer to the NICU, typically 10 minutes after birth.
Secondary outcome [4] 384629 0
Apgar scores at 1 and 5 minutes between groups.

This information is recorded in the existing medical records.
Timepoint [4] 384629 0
At 1 and 5 minutes after birth.
Secondary outcome [5] 384630 0
Percent of infants receiving surfactant and method of administration in each group.

This information is recorded in the existing medical records.
Timepoint [5] 384630 0
Within 72 hours of birth.
Secondary outcome [6] 384632 0
Percent intubation and mechanical ventilation within the first 72 hours after birth in each group.

This information is recorded in the existing medical records.
Timepoint [6] 384632 0
Within 72 hours of birth.
Secondary outcome [7] 384634 0
Days of mechanical ventilation during hospital admission in each group.

This information is recorded in the existing medical records.
Timepoint [7] 384634 0
From birth to hospital discharge.
Secondary outcome [8] 384635 0
Rates of chronic lung disease (need for respiratory support or oxygen at 36 weeks corrected gestational age) in each group.

This information is recorded in the existing medical records.
Timepoint [8] 384635 0
From birth until hospital discharge.
Secondary outcome [9] 384636 0
Corrected gestational age of the infant successfully weaning off any respiratory support (supplemental oxygen and/or CPAP/HiFlow) in each group.

This information is recorded in the existing medical records.
Timepoint [9] 384636 0
Prior to hospital discharge.

This information is recorded in the existing medical records.
Secondary outcome [10] 384637 0
Adverse events prior to hospital discharge: including pneumothorax, intraventricular haemorrhage, necrotising enterocolitis, sepsis, periventricular leukomalacia, retinopathy of prematurity requiring surgical intervention, and mortality.

This information is recorded in the existing medical records.
Timepoint [10] 384637 0
Prior to hospital discharge.

This information is recorded in the existing medical records.

Eligibility
Key inclusion criteria
Inborn infants 23 0/7 to 31 6/7 weeks gestation born at MMC Clayton are eligible for this study.
Minimum age
23 Weeks
Maximum age
31 Weeks
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Infants will be excluded if they have a known congenital abnormality that significantly affects the cardiorespiratory system, i.e. congenital diaphragmatic hernia or cyanotic congenital heart defect.

Infants that are planned to receive comfort care only, i.e. not to receive resuscitation or initiation of intensive care, will be excluded.

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)
This is an unblinded, randomised controlled trial, at Monash Medical Centre (MMC) Clayton.

Once the neonatal resuscitation team has been called to attend the pending birth, the unborn patient will be randomised to nasal CPAP or facemask CPAP for initial respiratory support. Randomisation will be allocated by a member of the research team via the RedCAP web-based randomisation tool. RedCAP is a HIPAA-compliant, secure web application for building and managing databases. Monash Health Translational Precinct is an institutional partner and a member of the RedCAP Consortium. Prior to the impending birth, investigators will use RedCAP generate a study number, randomise the unborn infant, and tell the clinical team the treatment allocation. We have used RedCAP process to successfully to randomise infants requiring neonatal resuscitation in the Baby DUCC RCT (ACTRN12618000621213). Infants will be stratified by gestational age, 23 and 0/7 to 27 and 6/7 weeks and 28 and 0/7 to 31 and 6/7 weeks.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be allocated by a member of the research team via the RedCAP web-based randomisation tool. RedCAP is a HIPAA-compliant, secure web application for building and managing databases. Monash Health Translational Precinct is an institutional partner and a member of the RedCAP Consortium. Prior to the impending birth, investigators will use RedCAP generate a study number, randomise the unborn infant, and tell the clinical team the treatment allocation. We have used RedCAP process to successfully to randomise infants requiring neonatal resuscitation in the Baby DUCC RCT (ACTRN12618000621213). Infants will be stratified by gestational age, 23 and 0/7 to 27 and 6/7 weeks and 28 and 0/7 to 31 and 6/7 weeks.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Each patient will be assigned a study number and de-identified information will be entered into a database for analysis (Microsoft Excel, USA and IBM SPSS, USA). We will use means and SDs for normally distributed continuous variables, and medians and IQRs for variables with skewed distribution.

The primary outcome will be determined using a Fisher’s Exact test. Continuous variables will be compared using an independent samples t-test if normally distributed and a 2-sided Mann-Whitney U test for non-normally distributed data. Categorical variables will be compared using the Fisher’s exact test. Statistical significance will be considered at p<0.05.

Ninety percent of infants <32 weeks’ will initiate breathing by 1 minute after birth, breathing at an average of 25 seconds after birth. In published studies that are consistent with our data from our ongoing CLD QI initiative at Monash (2017-2019), over 60% of VPTI will require PPV and 25% will require intubation prior to transfer to the NICU. In the delivery room at Monash in 2019, 97% of eligible infants received respiratory support, 33% received CPAP as their maximum level of support, and 64% required PPV and/or intubation.

We hypothesise that 75% of infants who receive nasal CPAP as the initial respiratory management will be successfully managed on CPAP, defined as not requiring escalation to PPV and/or intubation in the delivery room, versus 45% of infants who receive facemask CPAP as initial respiratory management. Assuming an alpha of 0.05 and 90% power, we would need to study 122 infants, 61 in each arm. We anticipate that 10% of infants will be apneic at birth and will immediately require positive pressure ventilation as the first mode of respiratory support and that 3% of infants will not require any respiratory support. Therefore, we plan to study 150 infants, 75 in each arm. We will stratify for gestational age, 23 and 0/7 days to 27 6/7 days and 28 and 0/7 days to 31 and 6/7 days, and specify that each arm must have a minimum of 25 born at <28 weeks gestational age.

Over 180 eligible infants are born at MMC annually, including 55 infants born at <28 weeks’ gestational age. We anticipate requiring 18 months to complete enrolment and an additional 4 months to follow the last enrolled infant until hospital discharge.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
2/11/2020
Actual
Date of last participant enrolment
Anticipated
2/05/2022
Actual
Date of last data collection
Anticipated
8/08/2022
Actual
Sample size
Target
150
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 17078 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment postcode(s) [1] 30751 0
3168 - Clayton

Funding & Sponsors
Funding source category [1] 306205 0
Hospital
Name [1] 306205 0
Monash Children's Hospital
Country [1] 306205 0
Australia
Primary sponsor type
Hospital
Name
Monash Medical Centre-Clayton
Address
246 Clayton Road, Clayton VIC 3168
Country
Australia
Secondary sponsor category [1] 306679 0
University
Name [1] 306679 0
The Ritchie Centre, Hudson Institute of Medical Research, Monash University
Address [1] 306679 0
246 Clayton Road, Clayton VIC 3168
Country [1] 306679 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306417 0
Monash Health Human Research Ethics Committee
Ethics committee address [1] 306417 0
Monash Medical Centre, Clayton
246 Clayton Road, Clayton, VIC
3168
Ethics committee country [1] 306417 0
Australia
Date submitted for ethics approval [1] 306417 0
10/02/2020
Approval date [1] 306417 0
06/03/2020
Ethics approval number [1] 306417 0
RES-20-0000-102A

Summary
Brief summary
Non-invasive, continuous positive airway pressure (CPAP) immediately after birth of a very preterm infant (“VPTI,” <32 weeks’ gestational age at birth) is currently recommended as the standard of care during the stabilisation of preterm infants following birth. After birth, the infant must rapidly transition from a fluid filled lung, and dependence on the placenta for oxygenation and the elimination of carbon dioxide, to an aerated lung that successfully exchanges gases. CPAP supports the transition from fetal to newborn physiology by providing a distending pressure to the lung, thus maintaining a functional residual capacity (FRC) and enabling oxygenation and ventilation.

Preterm infants who are successfully managed with CPAP versus mechanical ventilation via an endotracheal tube have increased survival without chronic lung disease, which improves long-term neurodevelopmental outcomes. Caffeine, and minimally invasive surfactant therapy (MIST) are other key treatments after admission to the NICU to avoid intubation and mechanical ventilation. Following stabilisation on CPAP, caffeine and MIST may be administered to further optimise respiratory support and reduce the risk of requiring intubation and mechanical ventilation, ultimately reducing the incidence of death and chronic lung disease in our patients.

97% of VPTIs at Monash require respiratory support to facilitate stabilisation. Current neonatal resuscitation training programs advocate a trial of CPAP via a facemask that covers the infant’s nose and mouth. An adequate seal is difficult to achieve and the use of a facemask has the additional adverse effect of high compressive forces being applied to the infant’s face and head during resuscitation regardless of which brand of facemask is used, and even with the use of adjunct respiratory monitoring. Ninety percent of VPTIs will initiate spontaneous breathing by 1 minute after birth. Despite VPTIs commonly having a good respiratory drive, respiratory support is nearly always indicated because of respiratory distress syndrome caused by the immature lungs. In this situation, facemask CPAP has a high failure rate due to stimulation of the trigeminal nerves which cause apnea, bradycardia, and hypoxia.

Our multidisciplinary team has over a year of experience with nasal CPAP at birth and we have equipoise between providing initial respiratory support in the delivery room with nasal CPAP versus facemask CPAP. We believe that nasal CPAP may be a more effective method of supporting the VPTI than facemask CPAP, specifically maintaining adequate spontaneous breathing and reducing the need for PPV, supplemental oxygen, and intubation in the delivery room. We believe a randomised controlled trial is warranted to test this hypothesis, in order to improve outcomes for high-risk, preterm infants, inform local practice, and provide critically important evidence to the global neonatal community.
Trial website
NA
Trial related presentations / publications
NA
Public notes

Contacts
Principal investigator
Name 103802 0
Dr Douglas Blank
Address 103802 0
Monash Health, Monash Newborn
246 Clayton Road, Clayton, VIC 3168
Country 103802 0
Australia
Phone 103802 0
+61 422305487
Fax 103802 0
Email 103802 0
[email protected]
Contact person for public queries
Name 103803 0
Dr Douglas Blank
Address 103803 0
Monash Health, Monash Newborn
246 Clayton Road, Clayton, VIC 3168
Country 103803 0
Australia
Phone 103803 0
+61 422305487
Fax 103803 0
Email 103803 0
[email protected]
Contact person for scientific queries
Name 103804 0
Dr Douglas Blank
Address 103804 0
Monash Health, Monash Newborn
246 Clayton Road, Clayton, VIC 3168
Country 103804 0
Australia
Phone 103804 0
+61 422305487
Fax 103804 0
Email 103804 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No, there is no plan for an IPD. There is no other similar trial currently running. We do not anticipate an IPD meta-analysis in the future.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
Current Study Results
No documents have been uploaded by study researchers.

Update to Study Results
Doc. No.TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
4150Plain language summaryNo In very preterm infants, nCPAP better supports spo... [More Details]

Documents added automatically
No additional documents have been identified.