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Trial registered on ANZCTR


Registration number
ACTRN12616000438459
Ethics application status
Approved
Date submitted
16/03/2016
Date registered
6/04/2016
Date last updated
28/02/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised trial of a nasal barrier dressing to reduce nasal trauma in very preterm infants receiving continuous positive airway pressure (CPAP) or nasal intermittent positive pressure ventilation (NIPPV) treatment: The ProNose study.
Scientific title
A randomised trial of a nasal barrier dressing to reduce nasal trauma in very preterm infants receiving CPAP/NIPPV treatment.
Secondary ID [1] 288653 0
None
Universal Trial Number (UTN)
Trial acronym
ProNose
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Nasal trauma in preterm infants receiving non invasive respiratory support treatment 297839 0
Condition category
Condition code
Injuries and Accidents 298012 298012 0 0
Other injuries and accidents
Respiratory 298013 298013 0 0
Other respiratory disorders / diseases
Reproductive Health and Childbirth 298383 298383 0 0
Complications of newborn

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Infants in the intervention group will have a Hydrocolloid nasal barrier dressing (Duoderm- a Polyurethane film coated with adhesive mass) applied by a neonatal intensive care unit (NICU) nurse over their nose within 1 hour of randomisation whilst receiving Continuous Positive Airway Pressure (CPAP) support or nasal intermittent positive pressure ventilation (NIPPV). This dressing will be applied within an hour of randomisation. The nasal barrier dressing size will be chosen as per the manufacturer's guidelines. The nasal barrier dressing provided by the manufacturer include velcro strips which can be used to maintain stable movement of prongs on the barrier dressing.
The nasal barrier dressing will continue to be applied during CPAP/NIPPV treatment for a period of at least two weeks, or until the infant is >30 weeks post menstrual age and >1250g, whichever is longer. The barrier dressing will be routinely changed every 72 hours.
Photographs of the nose without prongs in situ and with the barrier dressing removed will be taken at least twice weekly. The barrier dressing should be changed if it is no longer adherent to the infants' skin, if the dressing is damaged, or if there is a clinical need for access or visualisation of the area. The NICU nurse will assess the nose and upper lip area. A nasal trauma score will be generated and documented every time the nasal barrier dressing is changed and during every nursing care episode.
Intervention code [1] 294069 0
Prevention
Comparator / control treatment
Infants randomised to control group have no nasal barrier dressing applied. They have normal care with CPAP/NIPPV. Photographs of the nose without prongs in situ will be taken at least twice weekly.
Control group
Active

Outcomes
Primary outcome [1] 297528 0
Incidence of nasal trauma during CPAP/NIPPV support defined as Stage 1-4 on the Royal Women's Hospital Nasal Integrity and Pressure Chart:
Stage 0: Skin in intact. No sign of redness. (No nasal trauma)
Stage 1: Non blanchable erythema of intact skin. (Intact unbroken skin)
Stage 2: Partial thickness skin loss involving epidermis, dermis or both. (Abrasion, tear, blister)
Stage 3: Full thickness skin loss involving damage to or necrosis of subcutaneous tissue
Stage 4: Full thickness skin loss with extensive destruction, tissue necrosis or damage to supporting structures

Nasal trauma scores will be performed by the bedside nurse three times in each 24-hour period whilst CPAP/NIPPV support is applied.
Timepoint [1] 297528 0
The primary outcome period is: from randomisation, for a period of at least two weeks, and until the infant is >30 weeks post- menstrual age (PMA) and >1250 g weight, unless CPAP/NIPPV therapy is ceased earlier.
Secondary outcome [1] 321558 0
Incidence of Stage 2 or worse nasal trauma as documented on the Royal Women's Hospital (RWH) Nasal Integrity and Pressure form
Timepoint [1] 321558 0
From randomisation, for a period of at least two weeks, and until the infant is >30 weeks post- menstrual age (PMA) and >1250 g weight, unless CPAP/NIPPV therapy is ceased earlier.
Secondary outcome [2] 321814 0
Incidence of Stage 2 or worse nasal trauma on blinded review of nasal photographs: Throughout the primary outcome period, whilst an infant is receiving CPAP/NIPPV, standardised photographs will be taken of the nares and nasal septum by a trial investigator at least twice weekly during nursing cares, without the nasal prongs or barrier dressing (if applicable) in situ, and scored by a blinded investigator.
Timepoint [2] 321814 0
From randomisation, for a period of at least two weeks, and until the infant is >30 weeks post- menstrual age (PMA) and >1250 g weight, unless CPAP/NIPPV therapy is ceased earlier.
Secondary outcome [3] 321815 0
Number of nasal barrier dressings used in the Barrier Group. This will be determined by the number of barrier dressing changes recorded by the NICU nurse on a separate document, 'Barrier Dressing Replacement Form.'
Timepoint [3] 321815 0
From randomisation, for a period of at least two weeks, and until the infant is >30 weeks post- menstrual age (PMA) and >1250 g weight, unless CPAP/NIPPV therapy is ceased earlier.
Secondary outcome [4] 321816 0
Incidence of altered mode of respiratory support by the clinical team in response to nasal trauma, recorded on patient medical charts by NICU nurse.
Timepoint [4] 321816 0
From randomisation, for a period of at least two weeks, and until the infant is >30 weeks post- menstrual age (PMA) and >1250 g weight, unless CPAP/NIPPV therapy is ceased earlier.
Secondary outcome [5] 321817 0
Maximum set CPAP pressure used after randomisation, in cm H2O, recorded on patient medical charts by NICU nurse.
Timepoint [5] 321817 0
36 weeks' PMA
Secondary outcome [6] 321818 0
Maximum fraction of inspired oxygen (FiO2) after randomisation measured by a pulse oximetry and recorded on patient medical charts by NICU nurse.
Timepoint [6] 321818 0
36 weeks' PMA
Secondary outcome [7] 321851 0
Duration of CPAP/NIPPV support after randomisation in days (where one day is defined as any use of CPAP/NIPPV on a calendar day).
Timepoint [7] 321851 0
36 weeks' PMA
Secondary outcome [8] 321853 0
Total duration of any respiratory support after randomisation in days (where one day is defined as any use of respiratory support [NIPPV, CPAP, HFNC, mechanical ventilation via an endotracheal tube] on a calendar day).
Timepoint [8] 321853 0
36 weeks' PMA
Secondary outcome [9] 321854 0
Duration of supplemental oxygen after randomisation in days (where one day is defined as any use of supplemental oxygen on a calendar day).
Timepoint [9] 321854 0
36 weeks' PMA
Secondary outcome [10] 321855 0
Incidence of chronic lung disease (CLD), defined as either receiving respiratory support or requiring supplemental oxygen at two time-points: 28 days of life, and 36 weeks’ PMA.
Timepoint [10] 321855 0
28 days of life, and 36 weeks' PMA
Secondary outcome [11] 321856 0
Incidence of any need for endotracheal ventilation after randomisation
Timepoint [11] 321856 0
36 weeks' PMA
Secondary outcome [12] 321857 0
Total length of admission in a tertiary neonatal intensive care unit after randomisation, in days (where one day is defined as being hospitalised on any part of a calendar day).
Timepoint [12] 321857 0
36 weeks' PMA
Secondary outcome [13] 321858 0
Incidence of pneumothorax (air leak from the lung) after randomisation, and whether the pneumothorax requires drainage via needle aspiration or insertion of an intercostal catheter. Diagnosis is based on clinical assessment and confirmed by chest X-ray.
Timepoint [13] 321858 0
36 weeks' PMA
Secondary outcome [14] 321859 0
Incidence of proven sepsis after randomisation, defined as a positive blood culture not thought to be a contaminant and treatment with antibiotics for at least 5 calendar days.
Timepoint [14] 321859 0
36 weeks' PMA
Secondary outcome [15] 321860 0
Incidence of necrotising enterocolitis Bell Stage 2 or above treated with antibiotics for at least 5 calendar days.
Timepoint [15] 321860 0
36 weeks' PMA
Secondary outcome [16] 322273 0
Cost of nasal barrier dressings used in the Barrier Group is determined by the number of barrier dressings used per recruit multiplied by unit cost of the barrier dressing.
Timepoint [16] 322273 0
From randomisation, for a period of at least two weeks, and until the infant is >30 weeks post- menstrual age (PMA) and >1250 g weight, unless CPAP/NIPPV therapy is ceased earlier.

Eligibility
Key inclusion criteria
1. Preterm infants <30 weeks' GA at birth or birth weight <1250 g, and
2. Commencing CPAP/NIPPV at <30 weeks' corrected GA or at <1250 g current weight, whether previously mechanically ventilated or not, and
3. Are expected to require at least 4 hours of CPAP support and
4. Have received <48 hours of continuous CPAP/NIPPV support prior to consent being obtained.
Minimum age
No limit
Maximum age
3 Months
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Gestation at birth 30 weeks' or above, and birth weight 1250 g or above.
2. Received 48 hours or more of continuous CPAP/NIPPV support prior to consent and randomisation.
3. Received 48 hours or more of CPAP/NIPPV support prior to consent and randomisation
4. Expected to receive <4 hours of CPAP support.
5. Infants with any documented nasal trauma prior to enrolment.
6. Facial features potentially precluding the use of binasal CPAP/NIPPV e.g. clept lip or palate, Pierre Robin Sequence, choanal atresia.

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)
All babies will be randomised individually. The trial statistician will provide sets of consecutively numbered, sealed opaque envelopes containing the assigned group, using varying block sizes. The envelope will be opened within a time frame of either at least 4 hours of CPAP support or less than 48 hours of CPAP/NIPPV to the infant when consent has been obtained.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated with variable block sizes
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
Statistical analysis will be performed by the investigators. Analysis will be by intention to treat. Pre-randomisation stratification is by GA: <28 weeks’ GA and 28 weeks’ GA or above. Data will be exported from an electronic database to an electronic statistical package for analysis.

Dichotomous outcomes (e.g. incidence of nasal trauma) will be compared using a Chi squared test. Continuous outcomes (e.g. time on CPAP) will be compared using the appropriate parametric (t-test) or non-parametric (Mann-Whitney U) test.

No interim analyses are planned.

This study requires recruitment of 206 infants to address the primary outcome. In 2014, 205 infants <30 weeks’ GA or <1250 g, who required respiratory support were born at the RWH (~18 infants per month). We anticipate a relatively high recruitment rate due to the timeframe available for recruitment, and the low intervention nature of the study. Based on recent recruitment rates for similar studies at the Women’s we anticipate 70% recruitment, meaning that we will aim to enrol 206 infants over a period of 18 months (~12 per month).

We aim to demonstrate a 40% reduction in nasal trauma rates in this study. Therefore, to detect an absolute reduction in the primary outcome from 50 to 30% (a relative reduction of 40%), with 80% power. Results will be considered statistically significant if the p value for the primary outcome is less than 0.05. This requires a total sample size of 206 infants.

Recruitment
Recruitment status
Stopped early
Data analysis
Data analysis is complete
Reason for early stopping/withdrawal
Participant recruitment difficulties
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] 5399 0
The Royal Women's Hospital - Parkville
Recruitment postcode(s) [1] 12912 0
3052 - Parkville

Funding & Sponsors
Funding source category [1] 293063 0
Hospital
Name [1] 293063 0
Neonatal Services, The Royal Women's Hospital
Address [1] 293063 0
20 Flemington Rd, Parkville
Melbourne VIC 3052
Country [1] 293063 0
Australia
Primary sponsor type
Hospital
Name
Neonatal Services, The Royal Women's Hospital
Address
20 Flemington Rd, Parkville
Melbourne VIC 3052
Country
Australia
Secondary sponsor category [1] 291842 0
None
Name [1] 291842 0
None
Address [1] 291842 0
None
Country [1] 291842 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294572 0
Royal Women's Hospital Human Research Ethics Committee
Ethics committee address [1] 294572 0
20 Flemington Road
Parkville VIC 3052
Ethics committee country [1] 294572 0
Australia
Date submitted for ethics approval [1] 294572 0
27/10/2015
Approval date [1] 294572 0
15/12/2015
Ethics approval number [1] 294572 0
15/31

Summary
Brief summary
Small and premature babies often need help to breathe after birth, sometimes for many weeks. Established methods of providing breathing support are Continuous Positive Airway Pressure (CPAP) and Nasal Intermittent Positive Pressure Ventilation (NIPPV). CPAP and NIPPV use warmed air and oxygen given into the baby’s nose using small soft plastic prongs. This is very effective, but sometimes the plastic prongs can cause the skin in and around the nose to become sore or damaged. Skin damage is particularly common during CPAP /NIPPV treatment in very preterm and tiny babies.
The aim of the ProNose study is to see whether using a barrier dressing over the nose can reduce damage to the nose in very small babies receiving CPAP/NIPPV. To work out whether the barrier makes a difference, we organise babies receiving CPAP/NIPPV into two groups one group will have the barrier dressing and the other will not. The group results are then compared to see if there is any difference in the number of babies who get a sore nose.
Babies can join this study if they are born before 30 weeks' gestation or weigh less than 1250 grams at birth, and need CPAP/NIPPV treatment. Some babies will need this from soon after birth; other babies will need support from a ventilator (breathing machine) to begin with, and become ready for CPAP/NIPPV later on.
When a baby is ready to start CPAP/NIPPV, or soon after they have started this, babies will be randomly placed in one of the two study groups: (1) using the barrier dressing (BARRIER group) or (2) normal care – without the barrier dressing (NO BARRIER group).
Babies in the BARRIER group will have the barrier dressing applied within the hour, and will continue to have the barrier dressing whenever they are receiving CPAP/NIPPV for at least 2 weeks, or until they are 30 weeks from the start of pregnancy and weigh more than 1250 grams, unless they stop CPAP/NIPPV before then. The barrier dressing material will be replaced when required, as assessed by the clinical teams.
Babies in both groups will be followed for the study throughout their time at the Women’s. We will also take regular photographs of babies' noses whilst they are in this study and on breathing support. This is so that we can objectively assess whether there is any injury to the nose.
The ProNose study will enroll 206 babies at the Women’s and will take about 18 months to complete.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 63986 0
Dr Brett Manley
Address 63986 0
The Royal Women's Hospital
Level 7, 20 Flemington Road
Parkville, VIC 3052
Australia
Country 63986 0
Australia
Phone 63986 0
+61383453766
Fax 63986 0
Email 63986 0
brett.manley@thewomens.org.au
Contact person for public queries
Name 63987 0
Miss Dilini Imbulana
Address 63987 0
The Royal Women's Hospital
Level 7, 20 Flemington Road
Parkville, VIC 3052
Australia
Country 63987 0
Australia
Phone 63987 0
+61433888735
Fax 63987 0
Email 63987 0
dilini.imbulana@thewomens.org.au
Contact person for scientific queries
Name 63988 0
Miss Dilini Imbulana
Address 63988 0
The Royal Women's Hospital
Level 7, 20 Flemington Road
Parkville, VIC 3052
Australia
Country 63988 0
Australia
Phone 63988 0
+61433888735
Fax 63988 0
Email 63988 0
dilini.imbulana@thewomens.org.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary