Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614001203640
Ethics application status
Approved
Date submitted
3/11/2014
Date registered
17/11/2014
Date last updated
18/12/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
High-flow nasal cannulae use in non-tertiary centres for early respiratory distress in newborn infants: The HUNTER trial.
Scientific title
A comparison of treatment failure rates between newborn infants randomised to either high-flow nasal cannulae or continuous positive airway pressure as primary respiratory support in Australian non-tertiary special care nurseries.
Secondary ID [1] 285157 0
Nil
Universal Trial Number (UTN)
Trial acronym
HUNTER
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Respiratory distress syndrome (RDS)
 292747 0
Transient tachypnoea of the newborn (TTN) 293466 0
Condition category
Condition code
Respiratory 293039 293039 0 0
Other respiratory disorders / diseases
Reproductive Health and Childbirth 293747 293747 0 0
Complications of newborn

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
High-flow nasal cannulae (HFNC) - heated, humidifed gas (blended air/oxygen) delivered at gas flows between 6-8 Litres per minute via the Fisher & Paykel 'Optiflow Junior' circuit and prongs. HFNC will be weaned/ceased when the infant has no supplemental oxygen requirement, or has required <25% supplemental oxygen for >24 hours.
Intervention code [1] 290006 0
Treatment: Other
Comparator / control treatment
Continuous positive airway pressure (CPAP) - the use of short binasal prongs or mask to deliver heated, humidifed gas (blended air/oxygen) using a "bubble" CPAP device (any brand of CPAP device may be used) with set pressures between 6-8 centimetres of water. CPAP will be weaned/ceased when the infant has no supplemental oxygen requirement, or has required <25% supplemental oxygen for >24 hours.
Control group
Active

Outcomes
Primary outcome [1] 292906 0
Treatment failure within 72 hours of randomisation. Treatment failure has occurred if any of the following conditions are satisfied within 72 hours of an infant being randomised:
1. The infant is receiving maximal therapy (CPAP 8 cm H2O or HFNC 8 L/min) and has a fraction of inspired oxygen (FiO2) greater than or equal to 0.40 for more than 1 hour to maintain peripheral oxygen saturation (SpO2) 91-95%
2. The infant is receiving maximal therapy (CPAP 8 cm H2O or HFNC 8 L/min) and has both a pH <7.20 and pCO2 >60 mm Hg on two blood gas samples (which can be capillary, venous or arterial). The first sample should be collected at least 1 hour after initiation of the assigned treatment, and the second taken at least 1 hour after the first.
3. The infant is receiving maximal therapy (CPAP 8 cm H2O or HFNC 8 L/min) and has >1 apnoea receiving positive pressure ventilation within any 24-hour period, or >6 apnoeas in any 6 hour period receiving intervention (stimulation or increased oxygen)
4. The treating paediatrician determines that urgent intubation and mechanical ventilation is required
5. The treating paediatrician determines that the infant requires transfer to a tertiary centre through consultation with the local newborn emergency transport service (NETS NSW or PIPER Victoria).
Timepoint [1] 292906 0
72 hours after randomisation
Secondary outcome [1] 309902 0
Cost-benefit analysis: A health economist will estimate differences between the interventions based on the costs of equipment, care in SCNs and NICUs, costs to the family, and the costs of transfer (both infant and maternal)
Timepoint [1] 309902 0
Discharge home from hospital
Secondary outcome [2] 310231 0
Air leak from the lung (pneumothorax) requiring drainage via needle thoraccentesis or intercostal catheter insertion
Timepoint [2] 310231 0
Discharge home from hospital
Secondary outcome [3] 310232 0
Mortality
Timepoint [3] 310232 0
Discharge home from hospital
Secondary outcome [4] 310233 0
Length of time (hours) requiring supplemental oxygen
Timepoint [4] 310233 0
Discharge home from hospital
Secondary outcome [5] 310234 0
Duration of any respiratory support (hours), including HFNC, CPAP, and mechanical ventilation, and duration of each type of respiratory support (hours)
Timepoint [5] 310234 0
Discharge home from hospital
Secondary outcome [6] 310235 0
Requirement for supplemental oxygen at 28 days of age, and at 36 weeks' corrected gestational age for infants born <32 weeks' gestation.
Timepoint [6] 310235 0
28 days of age, and 36 weeks' corrected gestational age for infants born <32 weeks' gestation
Secondary outcome [7] 310236 0
Mechanical ventilation via an endotracheal tube in the first 72 hours after randomisation, and at any time before discharge home from hospital
Timepoint [7] 310236 0
72 hours after randomisation, and before discharge home from hospital
Secondary outcome [8] 310237 0
Total length of hospital admission (days), and length of admission to a tertiary centre (days)
Timepoint [8] 310237 0
Discharge home from hospital
Secondary outcome [9] 310238 0
Nasal trauma, as recorded on a nasal trauma scoring chart during treatment with the assigned intervention
Timepoint [9] 310238 0
Discharge home from hospital
Secondary outcome [10] 310239 0
Weight gain (grams) from birth to hospital discharge
Timepoint [10] 310239 0
Discharge home from hospital
Secondary outcome [11] 310240 0
Parental satisfaction, measured using a validated questionnaire (Parental stress scale [PSS]-NICU)
Timepoint [11] 310240 0
Completed on the day of discharge home by the parent that was most in attendance in the nursery during their infant's admission, .
Secondary outcome [12] 311313 0
Proportion of infants fully breastfed at discharge
Timepoint [12] 311313 0
Discharge home from hospital
Secondary outcome [13] 311314 0
Number of days receiving any intravenous fluids
Timepoint [13] 311314 0
Discharge home from hospital
Secondary outcome [14] 311315 0
Number of days to reach full suck feeds, defined as tolerating suck feeds without any requirement for intravenous fluids or naso/orogastric feeds for >24 hours
Timepoint [14] 311315 0
Discharge home from hospital
Secondary outcome [15] 319896 0
Nursing workload, measured using a validated tool (PAONCIL score)
Timepoint [15] 319896 0
The nurse caring for the infant for the most time during each nursing shift will complete the survey at the end of the shift. Surveys will completed after each nursing shift whilst the infant remains on respiratory support with either HFNC or CPAP during the primary outcome period (72 hours after randomisation).



Eligibility
Key inclusion criteria
1. Gestational age 31 weeks' or above by best obstetric estimate
2. Birth weight >1200 grams
3. Age <24 hours
4. Admitted to the special care nursery of a participating centre
5. Require non-invasive breathing support after admission to the special care nursery, or require supplemental oxygen to maintain peripheral oxygen saturation 91-95% for >1 hour
Minimum age
0 Hours
Maximum age
24 Hours
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. After admission to the SCN, the infants has already received >4 hours of CPAP
2. Previous endotracheal intubation and positive pressure ventilation, or imediate need for endotracheal intubation as determined by the treating paediatrician
3. Known major congenital abnormality which may impact upon the infant's condition after birth (eg. complex congenital cardiac disease, upper airway obstruction, gastrointestinal malformations)
4. Any infant who is judged by their paediatrician to require transfer to a tertiary hospital for ongoing 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)
Consecutively numbered, sealed, opaque randomisation envelopes containing the assigned treatment will be used. After prospective consent has been obtained for an eligible infant, the envelope will be opened at the cotside and the infant will receive the assigned treatment immediately after.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Block randomisation using variable block sizes. Randomisation will be pre-stratified by centre, and according to gestational age at birth (<34 weeks'; 34 weeks' or more). Multiple births will be randomised individually.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Analysis will be by intention-to-treat. A per protocol analysis will also be performed for the primary outcome and any important differences reported. Data will be exported from an electronic database to an electronic statistical package for analysis.

This is a non-inferiority trial with a margin of non-inferiority of 10%. Based on data from all six potential participating centres, we estimate the rate of the primary outcome in the CPAP group will be 17%. A sample size of 750 infants (375 infants in each group) is required to demonstrate non-inferiority of HFNC with 90% power: i.e. to be 90% sure that the upper limit of a two-sided 95% CI will exclude a difference in favour of CPAP or more than 10% (www.sealedenvelope.com/power/binary-noninferior).


The difference between the groups in the incidence of the primary outcome will be investigated using risk difference (95% confidence interval). Subgroup analysis by gestational age at birth will be performed for the primary outcome and some secondary outcomes. Secondary dichomotous outcomes will be compared with risk difference (95% CI) and a Chi-squared test. Continuous secondary outcomes will be compared with the appropriate parametric or non-parametric test.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/01/2015
Actual
13/04/2015
Date of last participant enrolment
Anticipated
31/12/2018
Actual
28/11/2017
Date of last data collection
Anticipated
Actual
1/12/2017
Sample size
Target
750
Accrual to date
Final
768
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 2960 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment hospital [2] 2961 0
Sunshine Hospital - St Albans
Recruitment hospital [3] 2962 0
The Northern Hospital - Epping
Recruitment hospital [4] 2964 0
Wollongong Hospital - Wollongong
Recruitment hospital [5] 2965 0
Gosford Hospital - Gosford
Recruitment hospital [6] 4451 0
Box Hill Hospital - Box Hill
Recruitment hospital [7] 4452 0
Angliss Hospital - Upper Ferntree Gully
Recruitment hospital [8] 7164 0
Dandenong Hospital - Dandenong
Recruitment hospital [9] 7165 0
Casey Hospital - Berwick
Recruitment postcode(s) [1] 8667 0
2500 - Wollongong
Recruitment postcode(s) [2] 8668 0
3021 - St Albans
Recruitment postcode(s) [3] 8669 0
3076 - Epping
Recruitment postcode(s) [4] 8671 0
3220 - Geelong
Recruitment postcode(s) [5] 8672 0
2250 - Gosford
Recruitment postcode(s) [6] 10657 0
3128 - Box Hill
Recruitment postcode(s) [7] 10658 0
3156 - Ferntree Gully
Recruitment postcode(s) [8] 14922 0
3175 - Dandenong
Recruitment postcode(s) [9] 14923 0
3806 - Berwick

Funding & Sponsors
Funding source category [1] 290181 0
Other
Name [1] 290181 0
Newborn Research Centre, The Royal Women's Hospital
Country [1] 290181 0
Australia
Funding source category [2] 295197 0
Government body
Name [2] 295197 0
National Health and Medical Research Council (NHMRC), Australia
Country [2] 295197 0
Australia
Primary sponsor type
Other
Name
Newborn Research Centre, The Royal Women's Hospital
Address
Level 7, 20 Flemington Road Parkville, Victoria 3052
Country
Australia
Secondary sponsor category [1] 288892 0
None
Name [1] 288892 0
Address [1] 288892 0
Country [1] 288892 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291890 0
Royal Children's Hospital Human Research Ethics Committee
Ethics committee address [1] 291890 0
Ethics committee country [1] 291890 0
Australia
Date submitted for ethics approval [1] 291890 0
07/10/2014
Approval date [1] 291890 0
28/11/2014
Ethics approval number [1] 291890 0
HREC/14/RCHM/48

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

Contacts
Principal investigator
Name 50654 0
Dr Brett Manley
Address 50654 0
Newborn Research Centre
The Royal Women's Hospital
Level 7, 20 Flemington Road
Parkville, Victoria 3052
Country 50654 0
Australia
Phone 50654 0
+613 8345 3766
Fax 50654 0
Email 50654 0
[email protected]
Contact person for public queries
Name 50655 0
Brett Manley
Address 50655 0
Newborn Research Centre
The Royal Women's Hospital
Level 7, 20 Flemington Road
Parkville, Victoria 3052
Country 50655 0
Australia
Phone 50655 0
+613 8345 3766
Fax 50655 0
Email 50655 0
[email protected]
Contact person for scientific queries
Name 50656 0
Brett Manley
Address 50656 0
Newborn Research Centre
The Royal Women's Hospital
Level 7, 20 Flemington Road
Parkville, Victoria 3052
Country 50656 0
Australia
Phone 50656 0
+613 8345 3766
Fax 50656 0
Email 50656 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
EmbaseA multicentre, randomised controlled, non-inferiority trial, comparing nasal high flow with nasal continuous positive airway pressure as primary support for newborn infants with early respiratory distress born in Australian non-tertiary special care nurseries (the HUNTER trial): Study protocol.2017https://dx.doi.org/10.1136/bmjopen-2017-016746
EmbaseNasal high-flow therapy for newborn infants in special care nurseries.2019https://dx.doi.org/10.1056/NEJMoa1812077
EmbasePredicting Nasal High-Flow Treatment Success in Newborn Infants with Respiratory Distress Cared for in Nontertiary Hospitals.2020https://dx.doi.org/10.1016/j.jpeds.2020.07.037
N.B. These documents automatically identified may not have been verified by the study sponsor.