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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04372953




Registration number
NCT04372953
Ethics application status
Date submitted
27/04/2020
Date registered
4/05/2020
Date last updated
24/09/2020

Titles & IDs
Public title
Positive End-Expiratory Pressure (PEEP) Levels During Resuscitation of Preterm Infants at Birth (The POLAR Trial).
Scientific title
Positive End-Expiratory Pressure (PEEP) Levels During Resuscitation of Preterm Infants at Birth (The POLAR Trial).
Secondary ID [1] 0 0
POLAR #60303
Universal Trial Number (UTN)
Trial acronym
POLAR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lung Injury 0 0
Preterm Birth 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Injuries and Accidents 0 0 0 0
Other injuries and accidents
Reproductive Health and Childbirth 0 0 0 0
Complications of newborn
Reproductive Health and Childbirth 0 0 0 0
Childbirth and postnatal care
Reproductive Health and Childbirth 0 0 0 0
Fetal medicine and complications of pregnancy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Surgery - Positive End-Expiratory Pressure (PEEP)

Active Comparator: 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.

Experimental: 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.


Treatment: Surgery: 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:
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).

Intervention code [1] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
At 36 weeks post menstrual age.
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
From the time of birth until 72 hours post birth.
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
From the time of birth until 10 days post birth.
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
From the time of birth until 10 days of age.
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
From the time of birth until 72 hours post birth.
Secondary outcome [5] 0 0
The rate/incidence of grade 3 and 4 intraventricular haemorrhage within the first 72 hours of life, as assessed on ultrasound. - 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.
Timepoint [5] 0 0
From the time of birth until 72 hours post birth.
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
From the time of birth through transfer to NICU (within two hours from birth)
Secondary outcome [7] 0 0
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).
Timepoint [7] 0 0
At 36 weeks post menstrual age.
Secondary outcome [8] 0 0
Incidence of Death at 36 week PMA - This is defined as death at 36 weeks PMA (individual component of primary outcome)
Timepoint [8] 0 0
At 36 weeks post menstrual age.
Secondary outcome [9] 0 0
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)
Timepoint [9] 0 0
At 36 weeks post menstrual age.
Secondary outcome [10] 0 0
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)
Timepoint [10] 0 0
During hospital stay, on average until 36 weeks PMA.
Secondary outcome [11] 0 0
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
Timepoint [11] 0 0
36-week corrected PMA.
Secondary outcome [12] 0 0
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.
Timepoint [12] 0 0
36-week corrected PMA.
Secondary outcome [13] 0 0
Need for 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
Timepoint [13] 0 0
First 10 days after birth.
Secondary outcome [14] 0 0
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.
Timepoint [14] 0 0
Birth to 10 days of age.
Secondary outcome [15] 0 0
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)
Timepoint [15] 0 0
36 week PMA.
Secondary outcome [16] 0 0
Postnatal steroid use - Defined as the incidence of one or more course of postnatal steroids for the treatment of BPD
Timepoint [16] 0 0
36 week PMA.
Secondary outcome [17] 0 0
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.
Timepoint [17] 0 0
36 week PMA.
Secondary outcome [18] 0 0
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.
Timepoint [18] 0 0
Up to 44 weeks PMA
Secondary outcome [19] 0 0
Oxygen requirement at discharge to home - Defined as the incidence of infants being discharged home on any form of oxygen therapy
Timepoint [19] 0 0
Up to 44 weeks PMA
Secondary outcome [20] 0 0
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
Timepoint [20] 0 0
72 hours of age.

Eligibility
Key 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).
Minimum age
23 Weeks
Maximum age
28 Weeks
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
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,WA
Recruitment hospital [1] 0 0
The Royal Women's Hospital, Melbourne Australia - Parkville
Recruitment hospital [2] 0 0
King Edward Memorial Hospital - Subiaco
Recruitment postcode(s) [1] 0 0
- Parkville
Recruitment postcode(s) [2] 0 0
6008 - Subiaco

Funding & Sponsors
Primary sponsor type
Other
Name
Murdoch Childrens Research Institute
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Children's Hospital of Philadelphia
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief 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.
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.
Trial website
https://clinicaltrials.gov/show/NCT04372953
Trial related presentations / 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.
Public notes

Contacts
Principal investigator
Name 0 0
David Tingay, MBBS FRACP
Address 0 0
Royal Children's Hospital, Melbourne Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
David Tingay, MBBS FRACP
Address 0 0
Country 0 0
Phone 0 0
+61 3 9345 4023
Fax 0 0
Email 0 0
david.tingay@rch.org.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04372953