Positive End-Expiratory Pressure (PEEP) Levels During Resuscitation of Preterm Infants at Birth (The POLAR Trial).

NCT ID: NCT04372953

Last Updated: 2025-09-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

906 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-05-04

Study Completion Date

2028-05-30

Brief Summary

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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

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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:

1. Assessing whether individualising (dynamic) PEEP is superior to static PEEP
2. 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
3. The optimal PEEP strategy to use
4. 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:

1. 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.
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).
3. 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:

1. Increase survival without BPD (primary outcome); and
2. 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:

1. Australia - The Murdoch Children's Research Institute/Royal Women's Hospital, Melbourne, AUS
2. The Netherlands - Amsterdam University Medical Centre, Netherlands, EU
3. The United Kingdom - The University of Oxford / National Perinatal Epidemiology Unit (NPEU), Oxford, UK, and
4. North America - the Hospital of the University of Pennsylvania, Pennsylvania, USA.

Conditions

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Lung Injury Preterm Birth

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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).
Primary Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Outcome Assessors
The clinical team within the Delivery Room managing enrolled and randomised infants will not be masked/blinded to the intervention.

Members of the Research Team at participating sites will also not be masked/blinded to the intervention.

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.

Study Groups

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Static PEEP Group

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.

Group Type ACTIVE_COMPARATOR

Positive End-Expiratory Pressure (PEEP)

Intervention Type PROCEDURE

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).

Dynamic PEEP Group

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.

Group Type EXPERIMENTAL

Positive End-Expiratory Pressure (PEEP)

Intervention Type PROCEDURE

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).

Interventions

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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).

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* 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).

Exclusion Criteria

* 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.
Minimum Eligible Age

23 Weeks

Maximum Eligible Age

28 Weeks

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Pennsylvania

OTHER

Sponsor Role collaborator

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

OTHER

Sponsor Role collaborator

University of Oxford

OTHER

Sponsor Role collaborator

Murdoch Childrens Research Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David Tingay, MBBS FRACP

Role: PRINCIPAL_INVESTIGATOR

Royal Children's Hospital

Locations

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University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status RECRUITING

Sharp Mary Birch Hospital for Women & Newborns

San Diego, California, United States

Site Status RECRUITING

Indiana University / Riley Children Health at Indiana University Health

Indianapolis, Indiana, United States

Site Status RECRUITING

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Mater Misericordiae

South Brisbane, Queensland, Australia

Site Status RECRUITING

Women & Childrens Hospital Adelaide

Adelaide, South Australia, Australia

Site Status RECRUITING

Joan Kirner Women & Children's Hospital - VIC

Melbourne, Victoria, Australia

Site Status RECRUITING

The Royal Women's Hospital, Melbourne Australia

Parkville, Victoria, Australia

Site Status RECRUITING

King Edward Memorial Hospital

Subiaco, Western Australia, Australia

Site Status RECRUITING

Academic Teaching Hospital

Feldkirch, Feldkirch, Austria

Site Status RECRUITING

Antoine Beclere Medical Center / South Paris University Hospitals

Paris, Paris, France

Site Status RECRUITING

Careggi Hospital

Florence, Florence, Italy

Site Status RECRUITING

Ospedale Maggiore Policlinico

Milan, Milan, Italy

Site Status RECRUITING

Vittore Buzzi Children's Hospital / Ospedale dei Bambini

Milan, Milan, Italy

Site Status RECRUITING

San Gerardo Hospital

Monza, Milan, Italy

Site Status RECRUITING

Filippo del Ponte Hospital

Varese, Milan, Italy

Site Status RECRUITING

Gemelli University Hospital

Rome, Rome, Italy

Site Status RECRUITING

Amsterdam University Medical Centre

Amsterdam, Amsterdam, Netherlands

Site Status ACTIVE_NOT_RECRUITING

Amalia Children's Hospital Radboudumc

Nijmegen, Nijmegen, Netherlands

Site Status RECRUITING

Maxima Medical Centre

Veldhoven, Veldhoven, Netherlands

Site Status RECRUITING

Poznan University of Medical Sciences

Poznan, Poznan, Poland

Site Status WITHDRAWN

Birmingham Heartlands Hospital

Birmingham, England, United Kingdom

Site Status RECRUITING

Southmead Hospital

Bristol, England, United Kingdom

Site Status RECRUITING

James Cook University Hospital

Middlesbrough, England, United Kingdom

Site Status RECRUITING

Royal Infirmary Edinburgh

Edinburgh, Scotland, United Kingdom

Site Status NOT_YET_RECRUITING

Royal Hospital for Children

Glasgow, Scotland, United Kingdom

Site Status RECRUITING

University Hospital Wishaw

Wishaw, Scotland, United Kingdom

Site Status RECRUITING

University Hospitals Leicester

Leicester, , United Kingdom

Site Status RECRUITING

Countries

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United States Australia Austria France Italy Netherlands Poland United Kingdom

Central Contacts

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David Tingay, MBBS FRACP

Role: CONTACT

+61 3 9345 4023

Laura Galletta, BSc

Role: CONTACT

+61 3 9936 6448

Facility Contacts

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Sherry Courtney

Role: primary

Jenna Chancellor

Role: backup

Anup Katharia

Role: primary

Felix Innes

Role: backup

Bobbi Byrne

Role: primary

Hannah Rakow

Role: backup

Elizabeth Foglia

Role: primary

Sura Lee

Role: backup

Helen Liley

Role: primary

Suzanne Bates

Role: backup

Michael Stark, MD

Role: primary

Tara Crawford

Role: backup

Àrun Sett

Role: primary

Niranjan Abraham

Role: backup

Louise Owen

Role: primary

Lisa Kalos

Role: backup

Andrew Gill

Role: primary

Yen Kok

Role: backup

Burkhard Simma

Role: primary

Wolfgang Stelzl

Role: backup

Daniele De Luca, MD

Role: primary

Adele Demain

Role: backup

Carlo Dani, MD

Role: primary

Simone Pratesi

Role: backup

Anna Lavizzari, MD

Role: primary

Alessandra Mayer, MD

Role: backup

Francesco Cavigioli, MD

Role: primary

Gianluca Lista

Role: backup

Camilla Rigotti, MD

Role: primary

Emanuela Zannin, MD

Role: backup

Ilia Bresesti, MD

Role: primary

Massimo Agosti, MD

Role: backup

Giovanni Vento, MD

Role: primary

Claudia Fe

Role: backup

Willem de Boode

Role: primary

Hendrik Niemarkt, MD

Role: primary

Marieke Vervoorn

Role: backup

Harsha Gowda

Role: primary

Birmingham Heartlands Paed Research Team

Role: backup

Charles C Roehr, MD

Role: primary

Paula Brock

Role: backup

Prakash Kannan Loganathan, MD

Role: primary

Amanda Forster

Role: backup

David Quine

Role: primary

Joyce O'Shea, MD

Role: primary

Siobbhan Moore

Role: backup

Karen McCall, MD

Role: primary

Denise Vigni

Role: backup

Joe Fawke, MD

Role: primary

Jennifer Smith

Role: backup

References

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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.

Reference Type BACKGROUND
PMID: 30995069 (View on PubMed)

Other Identifiers

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POLAR #60303

Identifier Type: -

Identifier Source: org_study_id

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