Respiratory Distress Syndrome, NewbornPrePAPNCT07251790
Optimising Breathing Support at Extubation in Very Preterm Infants: A Clinical Study
A study testing Pre-extubation continuous positive airway pressure in people with Respiratory Distress Syndrome, Newborn and Respiratory Distress Syndrome in Premature Infant, run by Murdoch Childrens Research Institute at 3 sites in Australia.
Trial summary
Many babies born very preterm (<32 weeks of pregnancy) require support to breathe from a breathing machine (mechanical ventilator) via a breathing tube. Although this keeps babies alive, it can damage their lungs. Read more about this study
- Who is it for?
- Ages 0 hours and older
- Conditions the study is for
- Respiratory Distress Syndrome, Newborn, Respiratory Distress Syndrome in Premature Infant
- What is being tested?
- Pre-extubation continuous positive airway pressure
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 134 participants
- Where
- 3 sitesAustralia
- Study dates
- 4 May 2026to 31 Mar 2028
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 hours and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- The infant is admitted to participating NICU
- The infant is born between 22+0 to 29+6 weeks gestational age
- The infant has been on a form of invasive mechanical ventilation for at least 4 hours
- The infant is being electively extubated for the first time from invasive mechanical ventilation to nCPAP
- The infant is clinically stable (as per clinical and research team consensus)
- The parent(s) or legal guardian(s) provides prospective informed consent.
Who cannot join
- The infant is born <22 weeks or >30 weeks gestational age
- The infant has a major congenital anomaly involving the cardiac, respiratory or gastrointestinal systems, or a known genetic syndrome or diagnosis that might affect respiratory course and outcomes
- The infant has severe pulmonary hypoplasia due to anhydramnios or oligohydramnios before 22 weeks in which the neonatal clinician anticipates that pulmonary hypoplasia related respiratory failure will be the major respiratory problem in early postnatal life
- The infant is receiving invasive mechanical ventilation via nasotracheal intubation
- The infant is planned for extubation to any other mode of non-invasive respiratory support than nCPAP, or no respiratory support
- Refusal of informed consent from the parent(s), or the infant does not have a guardian who can provide informed consent.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Australia3 sites, 3 recruiting
- Recruiting
The Royal Women's Hospital
Melbourne, Victoria, 3050
Risha Bhatia, MBBCh MA FRACP PhD, +61383452762 ext. 61, risha.bhatia@thewomens.org.au
Georgia S Stephen, BBmedSc BBiomedSc(Hons), +61(0)424701924, georgia.stephen@mcri.edu.au
- Recruiting
The Royal Children's Hospital
Parkville, Victoria, 3052
Georgia S Stephen, BBmedSc BBiomedSc(Hons), +61(0)424701924, georgia.stephen@mcri.edu.au
David Tingay, MBBS FRACP, +61 3 9345 4023, david.tingay@rch.org.au
- Recruiting
Joan Kirner Women's and Children's Hospital
Saint Albans, Victoria, 3021
Arun Sett, MBBS(Hons) FRACP PhD, +61383451333, arun.sett@wh.org.au
Georgia S Stephen, BBmedSc BBiomedSc(Hons), +61(0)424701924, georgia.stephen@mcri.edu.au
About this study
Official title: PrePAP: Pre-Extubation Continuous Positive Airway Pressure in Very Preterm Infants: A Randomised Controlled Trial
Many babies born very preterm (<32 weeks of pregnancy) require support to breathe from a breathing machine (mechanical ventilator) via a breathing tube. Although this keeps babies alive, it can damage their lungs. To reduce this damage, doctors and nurses try to change babies to gentler breathing support that does not require a breathing tube. This is usually done using a method called nasal continuous positive airway pressure (nCPAP) that uses a nosepiece to deliver breaths. This process of removing the breathing tube is called "extubation". Many babies will need the breathing tube put back in after extubation (for various reasons) and this is independently associated with poorer outcomes.
This research study aims to compare two ways of performing extubation - both of which are already used regularly by doctors and nurses. The "standard extubation" approach involves taking a baby's breathing tube out first, then applying the nosepiece and starting nCPAP. The more recent approach, called "prePAP", involves applying the nosepiece and starting nCPAP before taking the breathing tube out. Previous research suggests that a prePAP approach may provide better support for babies during extubation. However, larger studies are required before this approach is more commonly used.
Read more
This study is investigating whether extubating the baby with prePAP is better than extubating the baby without prePAP.
The main question it aims to answer is: Does initiating nCPAP before extubation in very preterm babies reduce the fall in their oxygen levels post-extubation?
Read the detailed description
The PrePAP trial will investigate if extubation with prePAP (nCPAP commenced prior to extubation) compared to standard extubation practice (nCPAP commenced after extubation) reduces oxygen desaturation in the four hours immediately post-extubation, in very preterm infants being extubated for the first time within the first 30 days of life.
Many infants born very preterm (<32 weeks' gestation) are intubated at birth to receive respiratory support via invasive ventilation. While essential for survival, invasive ventilation can injure their underdeveloped lungs, disrupt lung development and increase the risk of bronchopulmonary dysplasia, a major cause of long-term respiratory morbidity.
Transitioning infants to non-invasive ventilation as soon as feasible is prioritised by clinicians. However, in very preterm infants, almost 40% of extubation attempts fail due to oxygen desaturation or lung collapse. Re-intubation due to extubation failure can induce further airway injury, cardiovascular instability, and oxygen desaturation, resulting in clinical deterioration and prolonged hospitalisation.
PrePAP has been recently suggested as a method of improving respiratory stability during extubation in preterm infants. PrePAP involves commencing nCPAP prior to extubation, with the intent to maintain lung volumes during extubation; preserving oxygenation from pre- to post-extubation. To date, there isn't any clinical evidence explaining the impact to the lungs when both mechanical ventilation and nCPAP are being applied, nor is there evidence that signals a benefit of using prePAP during extubation. Despite this, prePAP is already used in clinical practice and is described in certain neonatal intensive care unit (NICU) extubation guidelines in Australia.
The PrePAP trial is a prospective, multicentre, unblinded, randomised, controlled trial comparing extubation from mechanical ventilation to nCPAP with and without the application of prePAP in very preterm infants born <30 weeks gestational age at first extubation.
Very preterm infants who meet all inclusion (and no exclusion) criteria will be randomised to receive one of two extubation procedures, placing them in either the "Extubation with prePAP" arm or the "Extubation without prePAP" arm:
- Arm 1: Extubation with prePAP (intervention): nCPAP commenced prior to endotracheal tube removal
- Arm 2: Extubation without prePAP (control): nCPAP commenced following endotracheal tube removal
For both arms, the intervention period will begin with a 2-to-5-minute pre-extubation period (whilst the infant is still ventilated), followed by a post-extubation period of up to 4 hours, and a follow-up period of up to 7 days (168 hours). The primary outcome (lowest S/F ratio) is assessed only during the (up to) 4-hour post-extubation period.
The results of this trial will determine the appropriate clinical outcomes and end point for a definitive, larger randomised trial to inform clinical practice.
- Being tested
- Pre-extubation continuous positive airway pressure
- Medical subject headings
- Respiratory Distress Syndrome, Newborn
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pre-extubation continuous positive airway pressureProcedure or surgery
Also called PrePAP
Prior to extubation (2-to-5 minutes) a CPAP hat will be placed on the infant and the circuit set up. A nasal mask will be applied and nCPAP pressure will be commenced at 10 centimetres of water. Only after nCPAP has been in situ for 2 minutes (maximum 5 minutes) will the endotracheal tube be removed.
| Study group | Role | What they receive |
|---|---|---|
| Extubation with prePAP | Experimental | nCPAP commenced prior to endotracheal tube removal Receives: Procedure: Pre-extubation continuous positive airway pressure |
| Extubation without prePAP | No intervention | nCPAP commenced following endotracheal tube removal |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in peripheral oxygen saturation to fraction of inspired oxygen ratio (SF ratio) measured within 4 hours post-extubation, or until escalation to nasal intermittent positive pressure ventilation or re-intubation.
Measured: 0 minutes then each minute up to 15 minutes, then every 15 minutes up to 4 hours post-extubation.
Secondary outcomes (11)
CPAP level set at extubation (0 minutes).
Measured: Measured during the extubation procedure.
Minimum CPAP level set post-extubation (0 minutes to 4 hours).
Measured: Measured from extubation up to 4 hours post-extubation.
Maximum CPAP level set post-extubation (0 minutes to 4 hours).
Measured: Measured from extubation up to 4 hours post-extubation.
Incidence of increase in CPAP level post-extubation (0 minutes to 4 hours).
Measured: Completed for each participant at 4 hours post-extubation.
Change in peripheral oxygen saturation to fraction of inspired oxygen ratio (SF ratio) measured pre-extubation and within 4 hours post-extubation (-5 minutes to 4 hours).
Measured: Measured from 5 minutes pre-extubation up to 4 hours post-extubation.
Change in peripheral oxygen saturation (SpO2) measured pre-extubation and within 4 hours post-extubation (-5 minutes to 4 hours).
Measured: Measured from 5 minutes pre-extubation up to 4 hours post-extubation.
Change in fraction of inspired oxygen (FiO2) measured pre-extubation and within 4 hours post-extubation (-5 minutes to 4 hours).
Measured: Measured from 5 minutes pre-extubation up to 4 hours post-extubation.
Maximum fraction of inspired oxygen (FiO2) measured pre-extubation and within 4 hours post-extubation (-5 minutes to 4 hours).
Measured: Measured from 5 minutes pre-extubation up to 4 hours post-extubation.
Change in incidence of significant oxygen desaturation measured post-extubation (0 minutes to 4 hours).
Significant oxygen desaturation is defined as SpO2 <80% for >30 seconds
Measured: Measured from extubation up to 4 hours post-extubation.
Incidence of escalation to nasal intermittent positive pressure ventilation within 7 days post-extubation.
Measured: Completed for each participant at the end of their study period: 7 days post-extubation.
Incidence of re-intubation within 7 days post-extubation.
Measured: Completed for each participant at the end of their study period: 7 days post-extubation.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2025
- Study start4 May 2026
- Primary completion31 Mar 2028 (estimated)
- Study completion31 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Respiratory Distress Syndrome, NewbornStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Infants enrolled in the trial will be randomised to receive one of two extubation procedures, placing them in either the "Extubation with prePAP" arm or the "Extubation without prePAP" arm: 1. Arm 1: Extubation with prePAP (intervention): nCPAP commenced prior to endotracheal tube removal 2. Arm 2: Extubation without prePAP (control): nCPAP commenced following endotracheal tube removal For both arms, the intervention period will begin with a 2-to-5-minute pre-extubation period (whilst the infant is still ventilated), followed by a post-extubation period of up to 4 hours, and a follow-up period of up to 7 days (168 hours).
- Masking
- None (open label)
- Enrolment
- 134 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Murdoch Childrens Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Western Health, Australia, Royal Women's Hospital, Melbourne, Australia
- Responsible party
- Sponsor
- Investigators
- Georgia S Stephen, BBmedSc BBiomedSc(Hons), Principal investigator, Murdoch Childrens Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07251790
- Sponsor's protocol ID
- 120475
- Acronym
- PrePAP
- Status last verified
- Aug 2026
- First submitted
- 29 Sep 2025
- Last updated
- 26 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The de-identified data set collected for this analysis of the PrePAP trial will be available six months after publication of the primary outcome, if the below access criteria are met. The study protocol, statistical analysis plan and consent forms will also be available. The data may be obtained from the Murdoch Children's Research Institute (MCRI) by emailing georgia.stephen@mcri.edu.au, david.tingay@rch.org.au and mctc@mcri.edu.au.
Publications
Gaertner VD, Ruegger CM. Optimising success of neonatal extubation: Respiratory support. Semin Fetal Neonatal Med. 2023 Oct;28(5):101491. doi: 10.1016/j.siny.2023.101491. Epub 2023 Nov 18.
PubMed 37993322Bhatia R, Carlisle HR, Armstrong RK, Kamlin COF, Davis PG, Tingay DG. Extubation generates lung volume inhomogeneity in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2022 Jan;107(1):82-86. doi: 10.1136/archdischild-2021-321788. Epub 2021 Jun 23.
PubMed 34162692Plastina L, Gaertner VD, Waldmann AD, Thomann J, Bassler D, Ruegger CM. The DELUX study: development of lung volumes during extubation of preterm infants. Pediatr Res. 2022 Jul;92(1):242-248. doi: 10.1038/s41390-021-01699-w. Epub 2021 Aug 31.
PubMed 34465873