Lung InjuryPOLARNCT04372953
Positive End-Expiratory Pressure (PEEP) Levels During Resuscitation of Preterm Infants at Birth (The POLAR Trial).
A study testing Positive End-Expiratory Pressure (PEEP) in people with Lung Injury and Preterm Birth, run by Murdoch Childrens Research Institute at 27 sites in 7 countries.
Trial summary
Premature babies often need help immediately after birth to open their lungs to air, start breathing and keep their hearts beating. Opening their lungs can be difficult, and once open the under-developed lungs of premature babies will often collapse again between each breath. Read more about this study
- Who is it for?
- Ages 23 to 28 weeks
- Conditions the study is for
- Lung Injury, Preterm Birth
- What is being tested?
- Positive End-Expiratory Pressure (PEEP)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 906 participants
- Where
- 27 sitesin 7 countries
- Study dates
- 4 May 2021to 30 May 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 23 to 28 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Infants born between 23 weeks 0 days and 28 weeks 6 days PMA (by best obstetric estimate).
- Receives respiratory intervention (resuscitation) at birth with CPAP and/or positive pressure ventilation in the Delivery Room, to support transition and/or respiratory failure related to prematurity.
- Has a parent or other legally acceptable representative capable of understanding the informed consent document and providing consent on the participant's behalf either prospectively or after birth and randomisation if prenatal consent was not possible (at sites where the Ethics Committee permits waiver of prospective consent).
Who cannot join
- Not for active care based on assessment of the attending clinician or family decision
- Anticipated severe pulmonary hypoplasia due to rupture of membranes <22 weeks with anhydramnios or fetal hydrops
- Major congenital anomaly or anticipated alternative cause for respiratory failure
- Refusal of informed consent by their legally acceptable representative
- Does not have a guardian who can provide informed consent.
Trial locations and contacts
27 sites in 7 countries.
27 sites in 7 countries
United Kingdom7 sites
Birmingham Heartlands Hospital
Birmingham, England, B9 5SS
Southmead Hospital
Bristol, England
Royal Infirmary Edinburgh
Edinburgh, Scotland, EH16 4SA
Royal Hospital for Children
Glasgow, Scotland
University Hospitals Leicester
Leicester
James Cook University Hospital
Middlesbrough, England
University Hospital Wishaw
Wishaw, Scotland
Italy6 sites
Careggi Hospital
Florence
Ospedale Maggiore Policlinico
Milan
Vittore Buzzi Children's Hospital / Ospedale dei Bambini
Milan
San Gerardo Hospital
Monza, Milan, 20090
Gemelli University Hospital
Rome
Filippo del Ponte Hospital
Varese, Milan, 21100
Australia5 sites
Women & Childrens Hospital Adelaide
Adelaide, South Australia
Joan Kirner Women & Children's Hospital - VIC
Melbourne, Victoria, 3021
The Royal Women's Hospital, Melbourne Australia
Parkville, Victoria, 3052
Mater Misericordiae
South Brisbane, Queensland, 4101
King Edward Memorial Hospital
Subiaco, Western Australia, 6008
United States4 sites
Indiana University / Riley Children Health at Indiana University Health
Indianapolis, Indiana, 46202
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Sharp Mary Birch Hospital for Women & Newborns
San Diego, California, 92123
Netherlands3 sites
Amsterdam University Medical Centre
Amsterdam, 1105
Amalia Children's Hospital Radboudumc
Nijmegen, 6500
Maxima Medical Centre
Veldhoven, 5504
France1 site
Antoine Beclere Medical Center / South Paris University Hospitals
Paris
About this study
Premature babies often need help immediately after birth to open their lungs to air, start breathing and keep their hearts beating. Opening their lungs can be difficult, and once open the under-developed lungs of premature babies will often collapse again between each breath. To prevent this nearly all premature babies receive some form of mechanical respiratory support to aid breathing. Common to all types of respiratory support is the delivery of a treatment called positive end-expiratory pressure, or PEEP. PEEP gives air, or a mixture of air and oxygen, to the lung between each breath to keep the lungs open and stop them collapsing.
Currently, clinicians do not have enough evidence on the right amount, or level, of PEEP to give at birth. As a result, doctors around the world give different amounts (or levels) of PEEP to premature babies at birth.
Read more
In this study, the Investigators will look at 2 different approaches to PEEP to help premature babies during their first breaths at birth. At the moment, the Investigators do not know if one is better than the other. One is to give the same PEEP level to the lungs. The others is to give a high PEEP level at birth when the lungs are hardest to open and then decrease the PEEP later once the lungs are opened and the baby is breathing.
Very premature babies have a risk of long-term lung disease (chronic lung disease). The more breathing support a premature baby needs, the more likely the risk of developing chronic lung disease. The Investigators want to find out whether one method of opening the baby's lungs at birth results in them needing less breathing support.
This research has been initiated by a group of doctors from Australia, the Netherlands and the USA, all who look after premature babies.
Read the detailed description
All infants born <29 weeks' postmenstrual age (PMA) require positive end-expiratory pressure (PEEP) at birth. PEEP is a simple, feasible and cost-effective therapy to support extremely preterm infants that is used globally. The effective and safe level of PEEP to use after preterm birth remains the most important unanswered question in neonatal respiratory medicine.
The Investigators will undertake an international multi-centre randomised controlled trial to address in extremely preterm infants, whether the use of a high, dynamic PEEP level strategy to support the lung during stabilisation ('resuscitation') at birth, compared to the current practice of a static PEEP level, will reduce the rate of death or bronchopulmonary dysplasia (BPD).
This trial will address the following four key knowledge gaps:
- Assessing whether individualising (dynamic) PEEP is superior to static PEEP
- The uncertainty regarding applied pressure strategies to support the lung during stabilisation at birth arising from the lack of a properly powered, well-designed randomised trial specifically addressing important outcomes for respiratory support in the Delivery Room
- The optimal PEEP strategy to use
- Determining the differential effects of PEEP at different gestational ages.
For this study, the term PEEP refers to the delivery of positive pressure (via a bias flow of gas) to the lungs during expiration by any method of assisted respiratory support, this includes:
- Continuous Positive Applied Pressure (CPAP; a method of non-invasive respiratory support). During CPAP no other type of positive pressure is delivered as the infant supports tidal ventilation using her/his own spontaneous breathing effort. PEEP during CPAP has also been called 'continuous distending pressure.
- Positive Pressure Ventilation (PPV). During PPV PEEP is delivered between periods of an applied inflating pressure (PIP) delivered at a clinician-determined rate. PPV can be delivered via a mask or other non-invasive interface (also termed non-invasive positive pressure ventilation; NIPPV), or via an endotracheal tube (often termed continuous mechanical ventilation; CMV).
- High-frequency oscillatory ventilation (HFOV) or high-frequency jet ventilation. These are modes of invasive PPV in which PIP is delivered at very fast rates (>120 inflations per minute) and at very small tidal volumes. During HFOV a mean airway pressure is determined by the clinician which is equivalent to the PEEP during other modes. During high-frequency jet ventilation the clinician sets a PEEP similar to CMV.
As all of these modes of ventilation have a similar goal of applying a pressure to the lung during expiration (usually to prevent lung collapse) the term PEEP has the same physiological result despite different methods of application.
The specific aim of the trial is to establish whether the use of a high, dynamic 8-12 cmH2O PEEP level ('dynamic') strategy to support the lung during stabilisation at birth, compared with a static 5-6 cmH2O PEEP level ('static') strategy, increases the rate of survival without bronchopulmonary dysplasia (BPD) in extremely preterm infants born <29 weeks' PMA, and reduces rates of common neonatal morbidities.
The Investigators hypothesise that in preterm infants born <29 weeks PMA who receive respiratory support during stabilisation at birth, a high, dynamic PEEP strategy (i.e. PEEP 8-12 cmH2O individualised to clinical need) as compared to a standard, static PEEP of 5-6 cmH2O, will:
- Increase survival without BPD (primary outcome); and
- Reduce rates of common neonatal morbidities such as failure of non-invasive respiratory support in the first 72 hours of life (secondary outcome).
This trial is a phase III/IV, two parallel group, non-blinded, 1:1 randomised controlled, multi-national, multi-centre study comparing dynamic PEEP (dynamic group) with standard PEEP strategy (static group).
The intervention will take place in the Delivery Room. The intervention period will be from the time of birth until 20 minutes of life or transfer from Delivery Room to NICU (whatever comes first). The follow-up period will extend to 36 weeks PMA (primary endpoint), and 24 months corrected GA to determine important long-term neurodevelopmental and respiratory outcomes.
The clinical team within the Delivery Room managing enrolled and randomised infants will not be masked/blinded to the intervention. Clinicians need to be able to see the PEEP delivery device to assess efficacy of pressure delivery. The Research Coordinator/Study team at site will also not be masked/blinded to the intervention, as they will be entering trial data into the data management system.
Research staff based at the central Trial Coordinating Centre (TCC), the Data Coordinating Centre (DCCe) and the trial statistician will be blinded to assigned treatment.
There will be a total of 906 infants recruited (453 in the Dynamic group, 453 in the Static group), over 25 recruitment centres across Australia, Europe, the United Kingdom, the Middle East, Canada and North America.
The study will have Regional Coordinating Centres (RCCs) established in the following jurisdictions:
- Australia - The Murdoch Children's Research Institute/Royal Women's Hospital, Melbourne, AUS
- The Netherlands - Amsterdam University Medical Centre, Netherlands, EU
- The United Kingdom - The University of Oxford / National Perinatal Epidemiology Unit (NPEU), Oxford, UK, and
- North America - the Hospital of the University of Pennsylvania, Pennsylvania, USA.
- Conditions
- Lung Injury, Preterm Birth
- Being tested
- Positive End-Expiratory Pressure (PEEP)
- Keywords
- Resuscitation, Positive End-Expiratory Pressure (PEEP), Bronchopulmonary Dysplasia
- Medical subject headings
- Lung Injury, Premature Birth, Bronchopulmonary Dysplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Positive End-Expiratory Pressure (PEEP)Procedure or surgery
PEEP is the delivery of any level of positive pressure to the lungs during expiration, by any method of assisted respiratory support. As the intervention in the Delivery Room PEEP will be administered via any of:
- Continuous Positive Applied Pressure (CPAP; non-invasive respiratory support) During CPAP, no other type of positive pressure is delivered as the infant supports tidal ventilation using her/his own spontaneous breathing effort.
- Positive Pressure Ventilation (PPV) During PPV, PEEP is delivered between periods of an applied inflating pressure (PIP) delivered at a clinician-determined rate. PPV can be delivered via a mask or other non-invasive interface (also termed non-invasive positive pressure ventilation; NIPPV), or via an endotracheal tube (often termed continuous mechanical ventilation; CMV).
| Study group | Role | What they receive |
|---|---|---|
| Static PEEP Group | Active comparator | Delivery of PEEP at 5-6 cmH2O via a T-piece resuscitator using an initial fraction of inspired oxygen (FiO2) of 0.30 via local standard interface (facemask, nasopharyngeal tube or nasal prong). FiO2 and other aspects of respiratory care are then titrated using a standardised resuscitation algorithm. Receives: Procedure: Positive End-Expiratory Pressure (PEEP) |
| Dynamic PEEP Group | Experimental | Dynamic delivery of PEEP at 8 cmH2O via a T-piece resuscitator using an initial fraction of inspired oxygen (FiO2) of 0.30 via local standard interface (facemask, nasopharyngeal tube or nasal prong). PEEP levels increased step-wise to 10 and/or 12 cmH2O if FiO2/respiratory care needs to be escalated as per a standardised resuscitation algorithm.
If an infant shows evidence of respiratory improvement during resuscitative care, PEEP will be reduced in a stepwise method by 2 cmH2O each reduction, but to no lower than 8 cmH2O. Receives: Procedure: Positive End-Expiratory Pressure (PEEP) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The prevalence of the composite outcome of either death or bronchopulmonary dysplasia (BPD), as assessed by standard oxygen reduction test.
This is defined as the proportion of participants in the analysis set with a confirmed death date or a diagnosis of bronchopulmonary dysplasia (BPD), at 36 weeks post menstrual age.
Measured: At 36 weeks post menstrual age.
Secondary outcomes (23)
The rate/incidence of failure of non-invasive ventilation in first 72 hours, as assessed by intubation status.
This is defined as the proportion of participants in the analysis set requiring invasive ventilation (i.e. insertion of a Endotracheal Tube (ETT) within the first 72 hours after birth.
Measured: From the time of birth until 72 hours post birth.
The rate/incidence of death within the first 10 days of life, as assessed by date of death.
This is defined as the proportion of participants in the analysis set having dies within the first 10 days post birth.
Measured: From the time of birth until 10 days post birth.
Oxygen requirement ≥50% for 3 or more consecutive hours in first 72 hours
This is defined as highest FiO2 applied for 3 or more consecutive hours in the first 72 hours of age.
Measured: From the time of birth until 72 hours post birth.
Supplementary oxygen use
This is defined as highest FiO2 in the delivery room, and then at 24 hours, 72 hours, 7 days and 10 days of age.
Measured: From the time of birth until 10 days of age.
The rate/incidence of surfactant therapy requirement within the first 72 hours of life, as assessed by surfactant therapy status.
This is defined as the proportion of participants in the analysis set requiring surfactant therapy within the first 72 hours post birth.
Measured: From the time of birth until 72 hours post birth.
The rate/incidence of grade 3 and 4 intraventricular haemorrhage within the first 72 hours of life, as defined via imaging.
This is defined as the proportion of participants in the analysis set requiring experiencing a grade 3 or 4 intraventricular haemorrhage, within the first 72 hours post birth.
Measured: From the time of birth until 72 hours post birth.
The rate/incidence of treatment failure within the delivery room, as assessed by intubation status.
This is defined as the proportion of participants in the analysis set requiring intubation (i.e. insertion of a Endotracheal Tube (ETT) within the delivery room, but prior to transfer to NICU.
Measured: From the time of birth through transfer to NICU (within two hours from birth)
The grade of bronchopulmonary dysplasia (BPD), based on the results of an oxygen reduction test.
This is defined as the grade bronchopulmonary dysplasia (BPD) assigned according to the results of an oxygen reduction test and mode or respiratory support at 36 weeks PMA (see Jensen et al Am J Resp Crit Care Med 2019;200:751-759).
Measured: At 36 weeks post menstrual age.
Incidence of Death at 36 week PMA
This is defined as death at 36 weeks PMA (individual component of primary outcome)
Measured: At 36 weeks post menstrual age.
Incidence of Bronchopulmonary dysplasia (BPD) at 36 week PMA
This is defined as the incidence of BPD at 36 weeks PMA (individual component of primary outcome)
Measured: At 36 weeks post menstrual age.
Incidence of air leak and/or pulmonary interstitial emphysema (defined on chest radiograph; CXR) in the first 10 days after birth
Any airleak, defined as Pneumothorax, pulmonary interstitial emphysema and/or pneumomediastimum, diagnosed by chest radiology within the first 10 days after birth.
Measured: Birth to 10 days of age.
Airleak
Any airleak, defined as Pneumothorax, pulmonary interstitial emphysema and/or pneumomediastimum, diagnosed by chest radiology. Airleak will be coded as occurring in the delivery room, in first 10 days of life, during hospital stay and if requiring drainage (e.g. via a chest tube)
Measured: During hospital stay, on average until 36 weeks PMA.
Retinopathy of prematurity (stage 3 or higher or requiring treatment)
Defined as retinopathy of prematurity (stage 3 or higher or requiring treatment) diagnosed by ophthalmological examination at or before 36-week corrected PMA
Measured: 36-week corrected PMA.
Significant brain injury (IVH grade 3 or 4, periventricular leukomalacia)
Significant brain injury (IVH grade 3 or 4, periventricular leukomalacia) at or before 36-week corrected PMA as assessed by ultrasound or MRI cranial imaging.
Measured: 36-week corrected PMA.
Invasive ventilation at day 10 of age
The rates of invasive ventilation (placement of an endotracheal tube for >4 hours) by day 7 and 10 of age
Measured: First 10 days after birth.
Highest PEEP used during non-invasive ventilation
Defined as the highest PEEP used during non-invasive ventilation in the NICU (after delivery room management) at 24 hours, 72 hours, 7 and 10 days of age.
Measured: Birth to 10 days of age.
Duration of respiratory support
Defined as the total number of days of all forms of respiratory support (supplementary oxygen therapy, non-invasive and invasive ventilation)
Measured: 36 week PMA.
Postnatal steroid use
Defined as the incidence of one or more course of postnatal steroids for the treatment of BPD
Measured: 36 week PMA.
Inotrope use
Defined as the incidence of the administration of one or more inotropic agent by continuous infusion (not as a resuscitative agent) for more than 1 hour.
Measured: 36 week PMA.
Length of stay in hospital
Defined as the total number of completed days in hospital related to the initial admission for management of preterm birth.
Measured: Up to 44 weeks PMA
Oxygen requirement at discharge to home
Defined as the incidence of infants being discharged home on any form of oxygen therapy
Measured: Up to 44 weeks PMA
Patent ductus arteriosus requiring medical or surgical therapy in first 72 hours
Defined as the incidence of patent ductus arteriosus requiring medical or surgical therapy in first 72 hours
Measured: 72 hours of age.
Meeting the protocol criteria for failure of non-invasive ventilation during the intervention period
This is defined as the proportion of participants in the analysis set who met the criteria for requiring invasive ventilation (i.e. insertion of a Endotracheal Tube (ETT) within the first 72 hours after birth.
Measured: Up to the first 20 minutes after commencing respiratory support following birth.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2020
- Study start4 May 2021
- Primary completion30 Nov 2026 (estimated)
- Study completion30 May 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Lung InjuryStudies of the same condition, open and under way.
- More trials run by Murdoch Childrens Research InstituteThe sponsor's other registered studies.
- 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Two parallel group, non-blinded, 1:1 randomised controlled, multi-national, multi-centre, trial comparing dynamic PEEP ( dynamic group) with standard PEEP strategy (static group).
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 906 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Murdoch Childrens Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- University of Pennsylvania, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), University of Oxford
- Responsible party
- Sponsor
- Investigators
- David Tingay, MBBS FRACP, Principal investigator, Royal Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04372953
- Sponsor's protocol ID
- POLAR #60303
- Acronym
- POLAR
- Status last verified
- Feb 2026
- First submitted
- 27 Apr 2020
- Last updated
- 19 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The de-identified data set collected for this analysis of the POLAR trial will be available six months after publication of the primary outcome. 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 by emailing david.tingay@rch.org.au and mctc@mcri.edu.au.
Publications
Jensen EA, Dysart K, Gantz MG, McDonald S, Bamat NA, Keszler M, Kirpalani H, Laughon MM, Poindexter BB, Duncan AF, Yoder BA, Eichenwald EC, DeMauro SB. The Diagnosis of Bronchopulmonary Dysplasia in Very Preterm Infants. An Evidence-based Approach. Am J Respir Crit Care Med. 2019 Sep 15;200(6):751-759. doi: 10.1164/rccm.201812-2348OC.
PubMed 30995069Tingay DG, Galletta L, Owen LS, Kamlin O, Orsini F, Stewart D, Foglia E, Perkins E, Miedema M, Courtney SE, Simma B, Stelzl W, Katheria A, Lavizzari A, Roehr CC, Lista G, Bezette J, van Kaam AH, Kirpalani H, Davis PG; POLAR Trial Investigators. Positive end-expiratory pressure levels during resuscitation of preterm infants at birth (POLAR): study protocol for a randomised controlled trial. Pediatr Res. 2026 May 12. doi: 10.1038/s41390-026-04942-4. Online ahead of print.
PubMed 42129370
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Positive End-Expiratory Pressure (PEEP) Levels During Resuscitation of Preterm Infants at Birth (The POLAR Trial).
- ClinicalTrials.gov ID
- NCT04372953
- Acronym / sponsor ID
- POLAR / POLAR #60303
- Conditions
- Lung Injury, Preterm Birth
- Keywords
- Resuscitation, Positive End-Expiratory Pressure (PEEP), Bronchopulmonary Dysplasia
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 906 participants (estimated)
- Lead sponsor
- Murdoch Childrens Research InstituteUniversity, hospital or other
- Collaborators
- University of Pennsylvania, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), University of Oxford
- Study start
- 4 May 2021 (actual)
- Primary completion
- 30 Nov 2026 (estimated)
- Study completion
- 30 May 2028 (estimated)
- First posted
- 4 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Premature babies often need help immediately after birth to open their lungs to air, start breathing and keep their hearts beating. Opening their lungs can be difficult, and once open the under-developed lungs of premature babies will often collapse again between each breath. To prevent this nearly all premature babies receive some form of mechanical respiratory support to aid breathing. Common to all types of respiratory support is the delivery of a treatment called positive end-expiratory pressure, or PEEP. PEEP gives air, or a mixture of air and oxygen, to the lung between each breath to keep the lungs open and stop them collapsing.
Currently, clinicians do not have enough evidence on the right amount, or level, of PEEP to give at birth. As a result, doctors around the world give different amounts (or levels) of PEEP to premature babies at birth.
In this study, the Investigators will look at 2 different approaches to PEEP to help premature babies during their first breaths at birth. At the moment, the Investigators do not know if one is better than the other. One is to give the same PEEP level to the lungs. The others is to give a high PEEP level at birth when the lungs are hardest to open and then decrease the PEEP later once the lungs are opened and the baby is breathing.
Very premature babies have a risk of long-term lung disease (chronic lung disease). The more breathing support a premature baby needs, the more likely the risk of developing chronic lung disease. The Investigators want to find out whether one method of opening the baby's lungs at birth results in them needing less breathing support.
This research has been initiated by a group of doctors from Australia, the Netherlands and the USA, all who look after premature babies.
Detailed description
All infants born <29 weeks' postmenstrual age (PMA) require positive end-expiratory pressure (PEEP) at birth. PEEP is a simple, feasible and cost-effective therapy to support extremely preterm infants that is used globally. The effective and safe level of PEEP to use after preterm birth remains the most important unanswered question in neonatal respiratory medicine.
The Investigators will undertake an international multi-centre randomised controlled trial to address in extremely preterm infants, whether the use of a high, dynamic PEEP level strategy to support the lung during stabilisation ('resuscitation') at birth, compared to the current practice of a static PEEP level, will reduce the rate of death or bronchopulmonary dysplasia (BPD).
This trial will address the following four key knowledge gaps:
- Assessing whether individualising (dynamic) PEEP is superior to static PEEP
- The uncertainty regarding applied pressure strategies to support the lung during stabilisation at birth arising from the lack of a properly powered, well-designed randomised trial specifically addressing important outcomes for respiratory support in the Delivery Room
- The optimal PEEP strategy to use
- Determining the differential effects of PEEP at different gestational ages.
For this study, the term PEEP refers to the delivery of positive pressure (via a bias flow of gas) to the lungs during expiration by any method of assisted respiratory support, this includes:
- Continuous Positive Applied Pressure (CPAP; a method of non-invasive respiratory support). During CPAP no other type of positive pressure is delivered as the infant supports tidal ventilation using her/his own spontaneous breathing effort. PEEP during CPAP has also been called 'continuous distending pressure.
- Positive Pressure Ventilation (PPV). During PPV PEEP is delivered between periods of an applied inflating pressure (PIP) delivered at a clinician-determined rate. PPV can be delivered via a mask or other non-invasive interface (also termed non-invasive positive pressure ventilation; NIPPV), or via an endotracheal tube (often termed continuous mechanical ventilation; CMV).
- High-frequency oscillatory ventilation (HFOV) or high-frequency jet ventilation. These are modes of invasive PPV in which PIP is delivered at very fast rates (>120 inflations per minute) and at very small tidal volumes. During HFOV a mean airway pressure is determined by the clinician which is equivalent to the PEEP during other modes. During high-frequency jet ventilation the clinician sets a PEEP similar to CMV.
As all of these modes of ventilation have a similar goal of applying a pressure to the lung during expiration (usually to prevent lung collapse) the term PEEP has the same physiological result despite different methods of application.
The specific aim of the trial is to establish whether the use of a high, dynamic 8-12 cmH2O PEEP level ('dynamic') strategy to support the lung during stabilisation at birth, compared with a static 5-6 cmH2O PEEP level ('static') strategy, increases the rate of survival without bronchopulmonary dysplasia (BPD) in extremely preterm infants born <29 weeks' PMA, and reduces rates of common neonatal morbidities.
The Investigators hypothesise that in preterm infants born <29 weeks PMA who receive respiratory support during stabilisation at birth, a high, dynamic PEEP strategy (i.e. PEEP 8-12 cmH2O individualised to clinical need) as compared to a standard, static PEEP of 5-6 cmH2O, will:
- Increase survival without BPD (primary outcome); and
- Reduce rates of common neonatal morbidities such as failure of non-invasive respiratory support in the first 72 hours of life (secondary outcome).
This trial is a phase III/IV, two parallel group, non-blinded, 1:1 randomised controlled, multi-national, multi-centre study comparing dynamic PEEP (dynamic group) with standard PEEP strategy (static group).
The intervention will take place in the Delivery Room. The intervention period will be from the time of birth until 20 minutes of life or transfer from Delivery Room to NICU (whatever comes first). The follow-up period will extend to 36 weeks PMA (primary endpoint), and 24 months corrected GA to determine important long-term neurodevelopmental and respiratory outcomes.
The clinical team within the Delivery Room managing enrolled and randomised infants will not be masked/blinded to the intervention. Clinicians need to be able to see the PEEP delivery device to assess efficacy of pressure delivery. The Research Coordinator/Study team at site will also not be masked/blinded to the intervention, as they will be entering trial data into the data management system.
Research staff based at the central Trial Coordinating Centre (TCC), the Data Coordinating Centre (DCCe) and the trial statistician will be blinded to assigned treatment.
There will be a total of 906 infants recruited (453 in the Dynamic group, 453 in the Static group), over 25 recruitment centres across Australia, Europe, the United Kingdom, the Middle East, Canada and North America.
The study will have Regional Coordinating Centres (RCCs) established in the following jurisdictions:
- Australia - The Murdoch Children's Research Institute/Royal Women's Hospital, Melbourne, AUS
- The Netherlands - Amsterdam University Medical Centre, Netherlands, EU
- The United Kingdom - The University of Oxford / National Perinatal Epidemiology Unit (NPEU), Oxford, UK, and
- North America - the Hospital of the University of Pennsylvania, Pennsylvania, USA.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Two parallel group, non-blinded, 1:1 randomised controlled, multi-national, multi-centre, trial comparing dynamic PEEP ( dynamic group) with standard PEEP strategy (static group).
| Arm | Type | Receives |
|---|---|---|
| Static PEEP Group | Active comparator | Procedure: Positive End-Expiratory Pressure (PEEP)Delivery of PEEP at 5-6 cmH2O via a T-piece resuscitator using an initial fraction of inspired oxygen (FiO2) of 0.30 via local standard interface (facemask, nasopharyngeal tube or nasal prong). FiO2 and other aspects of respiratory care are then titrated using a standardised resuscitation algorithm. |
| Dynamic PEEP Group | Experimental | Procedure: Positive End-Expiratory Pressure (PEEP)Dynamic delivery of PEEP at 8 cmH2O via a T-piece resuscitator using an initial fraction of inspired oxygen (FiO2) of 0.30 via local standard interface (facemask, nasopharyngeal tube or nasal prong). PEEP levels increased step-wise to 10 and/or 12 cmH2O if FiO2/respiratory care needs to be escalated as per a standardised resuscitation algorithm. If an infant shows evidence of respiratory improvement during resuscitative care, PEEP will be reduced in a stepwise method by 2 cmH2O each reduction, but to no lower than 8 cmH2O. |
Who may qualify
- Ages
- 23 to 28 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Infants born between 23 weeks 0 days and 28 weeks 6 days PMA (by best obstetric estimate).
- Receives respiratory intervention (resuscitation) at birth with CPAP and/or positive pressure ventilation in the Delivery Room, to support transition and/or respiratory failure related to prematurity.
- Has a parent or other legally acceptable representative capable of understanding the informed consent document and providing consent on the participant's behalf either prospectively or after birth and randomisation if prenatal consent was not possible (at sites where the Ethics Committee permits waiver of prospective consent).
Key exclusion criteria (5 listed)
- Not for active care based on assessment of the attending clinician or family decision
- Anticipated severe pulmonary hypoplasia due to rupture of membranes <22 weeks with anhydramnios or fetal hydrops
- Major congenital anomaly or anticipated alternative cause for respiratory failure
- Refusal of informed consent by their legally acceptable representative
- Does not have a guardian who can provide informed consent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Positive End-Expiratory Pressure (PEEP)PEEP is the delivery of any level of positive pressure to the lungs during expiration, by any method of assisted respiratory support. As the intervention in the Delivery Room PEEP will be administered via any of: 1. Continuous Positive Applied Pressure (CPAP; non-invasive respiratory support) During CPAP, no other type of positive pressure is delivered as the infant supports tidal ventilation using her/his own spontaneous breathing effort. 2. Positive Pressure Ventilation (PPV) During PPV, PEEP is delivered between periods of an applied inflating pressure (PIP) delivered at a clinician-determined rate. PPV can be delivered via a mask or other non-invasive interface (also termed non-invasive positive pressure ventilation; NIPPV), or via an endotracheal tube (often termed continuous mechanical ventilation; CMV). | Procedure or surgery | Dynamic PEEP Group, Static PEEP Group |
Primary outcome
The prevalence of the composite outcome of either death or bronchopulmonary dysplasia (BPD), as assessed by standard oxygen reduction test.
Time frame: At 36 weeks post menstrual age.
This is defined as the proportion of participants in the analysis set with a confirmed death date or a diagnosis of bronchopulmonary dysplasia (BPD), at 36 weeks post menstrual age.
23 secondary outcomes
The rate/incidence of failure of non-invasive ventilation in first 72 hours, as assessed by intubation status.
Time frame: From the time of birth until 72 hours post birth.
The rate/incidence of death within the first 10 days of life, as assessed by date of death.
Time frame: From the time of birth until 10 days post birth.
Oxygen requirement ≥50% for 3 or more consecutive hours in first 72 hours
Time frame: From the time of birth until 72 hours post birth.
Supplementary oxygen use
Time frame: From the time of birth until 10 days of age.
The rate/incidence of surfactant therapy requirement within the first 72 hours of life, as assessed by surfactant therapy status.
Time frame: From the time of birth until 72 hours post birth.
The rate/incidence of grade 3 and 4 intraventricular haemorrhage within the first 72 hours of life, as defined via imaging.
Time frame: From the time of birth until 72 hours post birth.
The rate/incidence of treatment failure within the delivery room, as assessed by intubation status.
Time frame: From the time of birth through transfer to NICU (within two hours from birth)
The grade of bronchopulmonary dysplasia (BPD), based on the results of an oxygen reduction test.
Time frame: At 36 weeks post menstrual age.
Incidence of Death at 36 week PMA
Time frame: At 36 weeks post menstrual age.
Incidence of Bronchopulmonary dysplasia (BPD) at 36 week PMA
Time frame: At 36 weeks post menstrual age.
Incidence of air leak and/or pulmonary interstitial emphysema (defined on chest radiograph; CXR) in the first 10 days after birth
Time frame: Birth to 10 days of age.
Airleak
Time frame: During hospital stay, on average until 36 weeks PMA.
Retinopathy of prematurity (stage 3 or higher or requiring treatment)
Time frame: 36-week corrected PMA.
Significant brain injury (IVH grade 3 or 4, periventricular leukomalacia)
Time frame: 36-week corrected PMA.
Invasive ventilation at day 10 of age
Time frame: First 10 days after birth.
Highest PEEP used during non-invasive ventilation
Time frame: Birth to 10 days of age.
Duration of respiratory support
Time frame: 36 week PMA.
Postnatal steroid use
Time frame: 36 week PMA.
Inotrope use
Time frame: 36 week PMA.
Length of stay in hospital
Time frame: Up to 44 weeks PMA
Oxygen requirement at discharge to home
Time frame: Up to 44 weeks PMA
Patent ductus arteriosus requiring medical or surgical therapy in first 72 hours
Time frame: 72 hours of age.
Meeting the protocol criteria for failure of non-invasive ventilation during the intervention period
Time frame: Up to the first 20 minutes after commencing respiratory support following birth.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2026.
- Background: PubMed 30995069Jensen EA, Dysart K, Gantz MG, McDonald S, Bamat NA, Keszler M, Kirpalani H, Laughon MM, Poindexter BB, Duncan AF, Yoder BA, Eichenwald EC, DeMauro SB. The Diagnosis of Bronchopulmonary Dysplasia in Very Preterm Infants. An Evidence-based Approach. Am J Respir Crit Care Med. 2019 Sep 15;200(6):751-759. doi: 10.1164/rccm.201812-2348OC.
- Derived from this study: PubMed 42129370Tingay DG, Galletta L, Owen LS, Kamlin O, Orsini F, Stewart D, Foglia E, Perkins E, Miedema M, Courtney SE, Simma B, Stelzl W, Katheria A, Lavizzari A, Roehr CC, Lista G, Bezette J, van Kaam AH, Kirpalani H, Davis PG; POLAR Trial Investigators. Positive end-expiratory pressure levels during resuscitation of preterm infants at birth (POLAR): study protocol for a randomised controlled trial. Pediatr Res. 2026 May 12. doi: 10.1038/s41390-026-04942-4. Online ahead of print.
- Individual participant dataSharing planned: Yes. The de-identified data set collected for this analysis of the POLAR trial will be available six months after publication of the primary outcome. 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 by emailing david.tingay@rch.org.au and mctc@mcri.edu.au.
Related trials for Lung Injury
Enrolling by invitation
Personalized Ventilator Settings for Patients on ECMO
Acute Respiratory Distress Syndrome (ARDS), Extracorporeal Membrane Oxygenation
Active, not recruiting
CT for Personalized Mechanical Ventilation
Ventilator-Induced Lung Injury, Sepsis Syndrome
RecruitingObservational study
Assessment of Blood Viscosity in ARDS (Acute Respiratory Distress Syndrome)
ARDS
Recruiting
Optimization of Saturation Targets And Resuscitation Trial (OptiSTART)
Premature Infants, Bronchopulmonary Dysplasia
RecruitingObservational study
Single-Cell Sequencing Analysis of Radiation Pneumonitis Signals In Patients Treated For Cancer With Radiotherapy
Radiation Pneumonitis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Tingay, MBBS FRACP principal investigator
Royal Children's Hospital
27 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Positive End-Expiratory Pressure (PEEP) in people with Lung Injury and Preterm Birth, run by Murdoch Childrens Research Institute at 27 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 19 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in United Kingdom, Italy, Australia, United States, Netherlands and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The prevalence of the composite outcome of either death or bronchopulmonary dysplasia (BPD), as assessed by standard oxygen reduction test. (time frame: At 36 weeks post menstrual age.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04372953, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2026.