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

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ClinicalTrials.gov Identifier: NCT04372953
Recruitment Status : Not yet recruiting
First Posted : May 4, 2020
Last Update Posted : September 24, 2020
Sponsor:
Collaborators:
Children's Hospital of Philadelphia
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Information provided by (Responsible Party):
Murdoch Childrens Research Institute

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.


Condition or disease Intervention/treatment Phase
Lung Injury Preterm Birth Procedure: Positive End-Expiratory Pressure (PEEP) Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 906 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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 (Outcomes Assessor)
Masking Description:

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

The Research Coordinator/Study team at site 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.

Primary Purpose: Prevention
Official Title: Positive End-Expiratory Pressure (PEEP) Levels During Resuscitation of Preterm Infants at Birth (The POLAR Trial).
Estimated Study Start Date : December 1, 2020
Estimated Primary Completion Date : August 1, 2026
Estimated Study Completion Date : December 30, 2027

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
Procedure: 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).

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.

Procedure: 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).




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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. ]
    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.

  2. 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. ]
    This is defined as the proportion of participants in the analysis set having dies within the first 10 days post birth.

  3. Supplementary oxygen use [ Time Frame: From the time of birth until 10 days of age. ]
    This is defined as highest FiO2 in the delivery room, and then at 24 hours, 72 hours, 7 days and 10 days of age.

  4. 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. ]
    This is defined as the proportion of participants in the analysis set requiring surfactant therapy within the first 72 hours post birth.

  5. The rate/incidence of grade 3 and 4 intraventricular haemorrhage within the first 72 hours of life, as assessed on ultrasound. [ Time Frame: From the time of birth until 72 hours post birth. ]
    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.

  6. 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) ]
    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.

  7. The grade of bronchopulmonary dysplasia (BPD), based on the results of an oxygen reduction test. [ Time Frame: At 36 weeks post menstrual age. ]
    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).

  8. Incidence of Death at 36 week PMA [ Time Frame: At 36 weeks post menstrual age. ]
    This is defined as death at 36 weeks PMA (individual component of primary outcome)

  9. Incidence of Bronchopulmonary dysplasia (BPD) at 36 week PMA [ Time Frame: At 36 weeks post menstrual age. ]
    This is defined as the incidence of BPD at 36 weeks PMA (individual component of primary outcome)

  10. Airleak [ Time Frame: During hospital stay, on average until 36 weeks PMA. ]
    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)

  11. Retinopathy of prematurity (stage 3 or higher or requiring treatment) [ Time Frame: 36-week corrected PMA. ]
    Defined as retinopathy of prematurity (stage 3 or higher or requiring treatment) diagnosed by ophthalmological examination at or before 36-week corrected PMA

  12. Significant brain injury (IVH grade 3 or 4, periventricular leukomalacia) [ Time Frame: 36-week corrected PMA. ]
    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.

  13. Need for invasive ventilation at day 10 of age [ Time Frame: First 10 days after birth. ]
    The rates of invasive ventilation (placement of an endotracheal tube for >4 hours) by day 7 and 10 of age

  14. Highest PEEP used during non-invasive ventilation [ Time Frame: Birth to 10 days of age. ]
    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.

  15. Duration of respiratory support [ Time Frame: 36 week PMA. ]
    Defined as the total number of days of all forms of respiratory support (supplementary oxygen therapy, non-invasive and invasive ventilation)

  16. Postnatal steroid use [ Time Frame: 36 week PMA. ]
    Defined as the incidence of one or more course of postnatal steroids for the treatment of BPD

  17. Inotrope use [ Time Frame: 36 week PMA. ]
    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.

  18. Length of stay in hospital [ Time Frame: Up to 44 weeks PMA ]
    Defined as the total number of completed days in hospital related to the initial admission for management of preterm birth.

  19. Oxygen requirement at discharge to home [ Time Frame: Up to 44 weeks PMA ]
    Defined as the incidence of infants being discharged home on any form of oxygen therapy

  20. Patent ductus arteriosus requiring medical or surgical therapy in first 72 hours [ Time Frame: 72 hours of age. ]
    Defined as the incidence of patent ductus arteriosus requiring medical or surgical therapy in first 72 hours



Information from the National Library of Medicine

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Ages Eligible for Study:   23 Weeks to 28 Weeks   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04372953


Contacts
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Contact: David Tingay, MBBS FRACP +61 3 9345 4023 david.tingay@rch.org.au
Contact: Laura Galletta, BSc +61 3 9936 6448 laura.galletta@mcri.edu.au

Locations
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Australia, Victoria
The Royal Women's Hospital, Melbourne Australia
Parkville, Victoria, Australia
Contact: Louise Owen       Louise.Owen@thewomens.org.au   
Contact: Omar Kamlin       Omar.Kamlin@thewomens.org.au   
Australia, Western Australia
King Edward Memorial Hospital
Subiaco, Western Australia, Australia, 6008
Contact: Andrew Gill       andy.gill@health.wa.gov.au   
Contact: Yen Kok       Chooi.Kok@health.wa.gov.au   
Sponsors and Collaborators
Murdoch Childrens Research Institute
Children's Hospital of Philadelphia
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Investigators
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Study Chair: David Tingay, MBBS FRACP Royal Children's Hospital, Melbourne Australia
Principal Investigator: Louise Owen The Royal Women's Hospital, Melbourne Australia
Principal Investigator: Omar Kamlin The Royal Women's Hospital, Melbourne Australia
Publications:
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Responsible Party: Murdoch Childrens Research Institute
ClinicalTrials.gov Identifier: NCT04372953    
Other Study ID Numbers: POLAR #60303
First Posted: May 4, 2020    Key Record Dates
Last Update Posted: September 24, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

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.

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: 6 months after publication of primary outcome.
Access Criteria:

Prior to releasing any data the following are required:

  1. A Data Transfer Agreement must be signed between relevant parties.
  2. The MCRI Sponsorship Committee must review and approve your protocol and statistical analysis plan which must include and describe how the data will be used and analysed.
  3. An Authorship Agreement to be agreed to and signed between relevant parties. The Agreement must include details regarding appropriate recognition. Authorship may not be justifiable but some form of acknowledgement is requested.
  4. Agreement to cover any additional costs relating to the provision of the data.
  5. Evidence of ethics approval or waiver of approval, to be compliant with the data transfer agreement and ethics requirements at our end.

Data will only be shared with a recognised research institution where the MCRI Sponsorship Committee has approved the proposed analysis plan.


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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Murdoch Childrens Research Institute:
Resuscitation
Positive End-Expiratory Pressure (PEEP)
Bronchopulmonary Dysplasia
Additional relevant MeSH terms:
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Lung Injury
Premature Birth
Obstetric Labor, Premature
Obstetric Labor Complications
Pregnancy Complications
Lung Diseases
Respiratory Tract Diseases
Thoracic Injuries
Wounds and Injuries