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Trial registered on ANZCTR


Registration number
ACTRN12617001204336p
Ethics application status
Submitted, not yet approved
Date submitted
31/05/2017
Date registered
17/08/2017
Date last updated
17/08/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Extreme preterm infant non-invasive surfactant trial (EPINIST)
Scientific title
Can prophylactic surfactant administration via a thin catheter to spontaneously breathing extreme preterm infants on nCPAP reduce need for mechanical ventilation compared to prophylactic surfactant with brief mechanical ventilation.
Secondary ID [1] 292095 0
'Nil known'
Universal Trial Number (UTN)
Trial acronym
EPINIST
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Respiratory distress syndrome 303516 0
Condition category
Condition code
Respiratory 302928 302928 0 0
Other respiratory disorders / diseases
Reproductive Health and Childbirth 303498 303498 0 0
Complications of newborn

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Thin catheter arm: If baby is born before 28 weeks gestation, the baby at birth, after initial resuscitation, will be allocated to receive in the delivery room surfactant (200mg/kg) endotracheally via a thin catheter (16G Angiocath) whilst your baby is breathing spontaneously on continuous positive airway pressure (CPAP – a form of non-invasive ventilation). The surfactant administration will be by the most experienced medical personnel at delivery (neonatologist/trainee neonatologist).
Intervention code [1] 298236 0
Treatment: Drugs
Intervention code [2] 298712 0
Treatment: Devices
Comparator / control treatment
Standard arm: Surfactant (200mg/kg) via an endotracheal tube and mechanical ventilation with an aim to extubate as early as possible. The surfactant administration will be by the most experienced medical personnel at delivery (neonatologist/trainee neonatologist).
Control group
Active

Outcomes
Primary outcome [1] 302320 0
Intubation and mechanical ventilation in the first week of life - yes/no.
Timepoint [1] 302320 0
First week after birth.
Primary outcome [2] 302877 0
Incidence of events requiring resuscitation during surfactant administration (events requiring IPPV and/or intubation). yes/no. Resuscitation record.
Timepoint [2] 302877 0
Delivery room resuscitation period.
Secondary outcome [1] 335467 0
Death or chronic lung disease (CLD) at 36 weeks post menstrual age [composite].
Timepoint [1] 335467 0
At 36 weeks post menstrual age.
Secondary outcome [2] 337286 0
Death at 36 weeks post menstrual age.
Timepoint [2] 337286 0
36 weeks corrected age.
Secondary outcome [3] 337287 0
Chronic lung disease at 36 weeks post menstrual age based on ANZNN definition using SHIFT test.
Timepoint [3] 337287 0
36 weeks corrected age.
Secondary outcome [4] 337288 0
Air leak (pneumothorax or pneumomediastinum) on Chest x-ray.
Timepoint [4] 337288 0
Any point during nursery admission.
Secondary outcome [5] 337289 0
Pulmonary haemorrhage [clinical recorded in medical record].
Timepoint [5] 337289 0
Any point during nursery admission.
Secondary outcome [6] 337290 0
Use of postnatal corticosteroid [medical record - prescription].
Timepoint [6] 337290 0
Any point during nursery admission.
Secondary outcome [7] 337291 0
Duration of mechanical ventilation in days {medical record].
Timepoint [7] 337291 0
Duration of nursery stay.
Secondary outcome [8] 337292 0
Duration of respiratory support (HFOV, IPPV, nCPAP or HFNC) in days {medical record].
Timepoint [8] 337292 0
Duration of nursery stay.
Secondary outcome [9] 337293 0
Days to last on oxygen {medical record].
Timepoint [9] 337293 0
Duration of nursery stay
Secondary outcome [10] 337294 0
Need for home oxygen {medical record].
Timepoint [10] 337294 0
At time of discharge from hospital
Secondary outcome [11] 337295 0
Duration of hospital stay in days {medical record].
Timepoint [11] 337295 0
Admission to discharge.
Secondary outcome [12] 337310 0
Intraventricular haemorrhage (any, severe including grade 3 and above) on head ultrasound.
Timepoint [12] 337310 0
Day 7.
Secondary outcome [13] 337311 0
Patent ductus arteriosus needing medical treatment or surgical ligation [confirmed on ultrasound, treatment documented in medical record].
Timepoint [13] 337311 0
Duration of nursery stay.
Secondary outcome [14] 337312 0
Cystic Periventricular leukomalacia on head ultrasound.
Timepoint [14] 337312 0
Day 28.
Secondary outcome [15] 337313 0
Brain injury defined as severe intraventricular haemorrhage or echodense intraparenchymal lesions or periventricular leukomalacia or porencephalic cysts or ventriculomegaly (97th percentile + 4mm), [head ultrasound]
Timepoint [15] 337313 0
Day 28.
Secondary outcome [16] 337314 0
Necrotising enterocolitis (Bell stage 2 or above) [clinical, x-ray or surgical diagnosis recorded in medical record].
Timepoint [16] 337314 0
Duration of nursery stay
Secondary outcome [17] 337315 0
Retinopathy of prematurity (any, severe including stage 3 and above) [ophthalmologist examination recorded in medical record].
Timepoint [17] 337315 0
Duration of nursery stay.
Secondary outcome [18] 337316 0
Neurodevelopmental disability assessed at 24 to 36 months postnatal corrected age defined as neurological abnormality including cerebral palsy on clinical examination, developmental delay more than two standard deviations below population mean on a standardized test of development, or blindness (visual acuity less than 6/60), or deafness (any hearing impairment requiring amplification) at any time after term corrected.
Timepoint [18] 337316 0
24 to 36 months postnatal corrected age.

Eligibility
Key inclusion criteria
1. Preterm infants born between 24 weeks and 0 days and 27 weeks and 6 days gestational age and less than 30 minutes age.
2. Informed consent has been received from a parent.
Minimum age
0 Hours
Maximum age
1 Hours
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Infants considered unlikely to survive.
2. Infants with congenital abnormality with potential to affect breathing or survival.
3. Infants considered unlikely to benefit from surfactant due to alternative diagnosis [eg midtrimester prolonged rupture membranes].
4. Infants whose mothers had severe clinical chorioamnionitis (fever greater than 38 degree celsius).

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)
Yes. Antenatal informed consent. Enrolled immediately before birth after eligibility confirmed. Randomised at delivery using sequentially numbered opaque sealed envelopes.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Random number generator by independent person.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
62 infants (31 each group) will be required to detect a 30% absolute reduction in the rate of intubation and ventilation in the first week after birth from 90% in the prophylactic / rescue surfactant group to 60% in the nCPAP with thin catheter surfactant group with a power of 80% at the p=0.05 level. For a 20% absolute risk reduction with 80% power at the p=0.05 level, 124 infants (62 each group) are required.

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)
NSW
Recruitment hospital [1] 8223 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 16282 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 296625 0
Self funded/Unfunded
Name [1] 296625 0
Address [1] 296625 0
Country [1] 296625 0
Primary sponsor type
Hospital
Name
Royal Prince Alfred Hospital
Address
Royal Prince Alfred Hospital
Missenden Road
Camperdown NSW 2050
Country
Australia
Secondary sponsor category [1] 295586 0
None
Name [1] 295586 0
Address [1] 295586 0
Country [1] 295586 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 297858 0
Sydney Local health district HREC
Ethics committee address [1] 297858 0
Research Development Office, Royal Prince Alfred Hospital, Missenden Road, CAMPERDOWN NSW 2050
Ethics committee country [1] 297858 0
Australia
Date submitted for ethics approval [1] 297858 0
31/05/2017
Approval date [1] 297858 0
Ethics approval number [1] 297858 0

Summary
Brief summary
Background: The majority of extremely premature infants receive mechanical ventilation despite current strategies for prevention. They remain at high risk of mortality, bronchopulmonary dysplasia (BPD) and other morbidities, and developmental disabilities. In an era of high use of antenatal corticosteroids for lung maturation and postnatal nCPAP, the optimal respiratory support strategy for extremely premature infants is currently unclear. Substantial practice variation exists including prophylactic intubation and surfactant either with immediate extubation or brief mechanical ventilation (goal <1 hour) and extubation to nCPAP, or nCPAP and rescue surfactant using various techniques.

Primary clinical hypothesis: To determine if early surfactant administration via a thin catheter to spontaneously breathing preterm infants on nCPAP will reduce need for mechanical ventilation without an increase in neonatal morbidity or mortality compared to prophylactic surfactant with brief mechanical ventilation.

Study objectives
In extremely premature infants, the pilot study aims to determine the following to inform a larger definitive trial:
1. The feasibility and tolerance of delivery room thin catheter instillation of surfactant.
2. Effectiveness of prophylactic thin catheter surfactant in preventing intubation and mechanical ventilation.
3. Optimal enrolment and randomisation procedures.

Study design
This is a pilot parallel open label randomised controlled pilot study trial to one of 2 strategies of respiratory support and surfactant delivery.

Study population
All infants born at 24 weeks and 0 days to 27 weeks and 6 days completed gestation.

Study interventions
Infants born at <28 weeks: all infants with parental consent will be enrolled at birth and randomised to either:
1. Intubation, surfactant and brief mechanical ventilation
2. Nasal continuous positive airway pressure (nCPAP) with thin catheter surfactant

Primary outcome [pilot study]
1. Intubation and mechanical ventilation
2. Incidence of events requiring resuscitation during surfactant administration (events requiring IPPV and/or intubation)

Secondary outcomes
Secondary outcomes include all major neonatal morbidities during hospital admission and neurodevelopmental outcomes at 3 years of age.

Power and Sample Size
62 infants (31 each group) will be required to detect a 30% absolute reduction in the rate of intubation and ventilation in the first week after birth from 90% in the prophylactic / rescue surfactant group to 60% in the nCPAP with thin catheter surfactant group with a power of 80% at the p=0.05 level. For a 20% absolute risk reduction with 80% power at the p=0.05 level, 124 infants (62 each group) are required.
Trial website
None
Trial related presentations / publications
None
Public notes
None

Contacts
Principal investigator
Name 75286 0
A/Prof David Osborn
Address 75286 0
RPA Newborn Care
Royal Prince Alfred Hospital
Missenden Road
Camperdown NSW 2050
Country 75286 0
Australia
Phone 75286 0
+61295158363
Fax 75286 0
+61295504375
Email 75286 0
david.osborn@sydney.edu.au
Contact person for public queries
Name 75287 0
A/Prof David Osborn
Address 75287 0
RPA Newborn Care
Royal Prince Alfred Hospital
Missenden Road
Camperdown NSW 2050
Country 75287 0
Australia
Phone 75287 0
+61295158363
Fax 75287 0
+61295504375
Email 75287 0
david.osborn@sydney.edu.au
Contact person for scientific queries
Name 75288 0
A/Prof David Osborn
Address 75288 0
RPA Newborn Care
Royal Prince Alfred Hospital
Missenden Road
Camperdown NSW 2050
Country 75288 0
Australia
Phone 75288 0
+61295158363
Fax 75288 0
+61295504375
Email 75288 0
david.osborn@sydney.edu.au

No data has been provided for results reporting
Summary results
Not applicable