PEEP Levels for Premature Birth

(POLAR Trial)

Recruiting at 31 trial locations

Overseen By Laura Galletta, BSc

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Murdoch Childrens Research Institute

Disqualifiers: Severe pulmonary hypoplasia, Major congenital anomaly, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

906 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether participants must stop taking their current medications.

What data supports the effectiveness of the treatment Positive End-Expiratory Pressure (PEEP) for premature birth?

Research shows that PEEP, when used in nasal continuous positive airway pressure (CPAP), can reduce the need for more invasive breathing support in very low birth weight infants with breathing problems. However, finding the right PEEP level is crucial, as too little or too much can lead to complications. ^{1 2 3 4 5}

Is Positive End-Expiratory Pressure (PEEP) generally safe for use in humans?

PEEP is generally used safely in newborns, infants, and children to help with breathing, but it can have complications like lung damage, decreased heart function, and increased pressure in the brain if not set correctly. It is important to tailor PEEP settings individually to minimize risks. ^{1 2 5 6 7}

How is the treatment PEEP different from other treatments for premature birth?

PEEP (Positive End-Expiratory Pressure) is unique because it helps keep the airways open in premature infants by maintaining a small amount of pressure in the lungs at the end of exhalation, which can improve breathing and gas exchange. Unlike other treatments, PEEP is specifically adjusted to prevent airway collapse and is used immediately after birth to support infants with underdeveloped lungs. ^{1 2 5 8 9}

What is the purpose of this trial?

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.

Research Team

David Tingay, MBBS FRACP

Principal Investigator

Royal Children's Hospital

Eligibility Criteria

The POLAR trial is for very premature infants born between 23 and 28 weeks who need help breathing at birth. It's not for babies with severe lung problems, major birth defects, or those whose families decide against aggressive care.

Inclusion Criteria

My newborn needed breathing support right after birth due to being premature.

I have a guardian who can consent to my participation in the study.

My baby was born between 23 and 28 weeks of pregnancy.

Exclusion Criteria

My baby is expected to have severe lung issues due to early water break or fluid buildup.

My legal representative has not agreed to the clinical trial.

Does not have a guardian who can provide informed consent

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Intervention

Dynamic or static PEEP levels are applied to support lung function during resuscitation at birth

20 minutes or until transfer to NICU

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness, including respiratory outcomes and neurodevelopmental assessments

36 weeks PMA

Long-term Follow-up

Assessment of long-term neurodevelopmental and respiratory outcomes

24 months corrected GA

Treatment Details

Interventions

• Positive End-Expiratory Pressure (PEEP)

Trial Overview This study tests two ways of using PEEP in resuscitation: a constant level versus starting high then lowering it. The goal is to see which method better prevents lung collapse without increasing the risk of chronic lung disease.

Participant Groups

Group I: Dynamic PEEP Group Experimental Treatment 1 Intervention

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 II: Static PEEP Group Active Control 1 Intervention

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.

Who Is Running the Clinical Trial?

Murdoch Childrens Research Institute

Lead Sponsor

Trials

90

Recruited

1,303,000+

University of Pennsylvania

Collaborator

Trials

2,118

Recruited

45,270,000+

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

Collaborator

Trials

722

Recruited

2,726,000+

University of Oxford

Collaborator

Trials

1,113

Recruited

21,220,000+

Findings from Research

Dynamic airway CT can help determine the optimal PEEP settings for infants with bronchopulmonary dysplasia (BPD) on long-term ventilator support, ensuring at least 50% airway patency.

In a study of 16 infants undergoing 17 CT exams, adjustments to PEEP were made based on CT findings, indicating that this imaging technique may improve management of ventilation in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel approach using volumetric dynamic airway computed tomography to determine positive end-expiratory pressure (PEEP) settings to maintain airway patency in ventilated infants with bronchopulmonary dysplasia. May, LA., Jadhav, SP., Guillerman, RP., et al.[2020]

A systematic review of 11 randomized control trials found no significant difference in hospital, 28-day, or ICU mortality rates between patients with acute respiratory distress syndrome (ARDS) treated with higher versus lower levels of positive end-expiratory pressure (PEEP).

The results indicate that using higher PEEP does not lead to better clinical outcomes in ARDS patients, suggesting that both higher and lower PEEP strategies can be considered safe and effective without a clear advantage for one over the other.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential Prognostic Analysis of Higher and Lower PEEP in ARDS Patients: Systematic Review and Meta-Analysis. Liang, M., Chen, X.[2023]

In a study of 18 neurosurgical intensive care patients, applying PEEP at 5 cm H2O did not affect intracranial pressure in those with normal levels, while higher PEEP levels (10 and 15 cm H2O) led to a slight increase in intracranial pressure, but this was not clinically significant as cerebral perfusion pressure remained stable.

For patients with increased intracranial pressure, varying PEEP levels did not significantly alter either intracranial pressure or cerebral perfusion pressure, suggesting that PEEP may be safely used without adverse effects on cerebral hemodynamics in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of varying levels of positive end-expiratory pressure on intracranial pressure and cerebral perfusion pressure. McGuire, G., Crossley, D., Richards, J., et al.[2022]

This study will compare the effects of higher (6-8 cmH2O) versus lower (3-5 cmH2O) levels of PEEP during nasal CPAP treatment in 216 preterm infants to determine which level is more effective in preventing the need for intubation and mechanical ventilation.

The research aims to establish the optimal PEEP level to improve treatment outcomes for respiratory distress syndrome in very low birth weight infants, potentially reducing the risk of ventilator-induced lung injury and chronic lung disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of two different nasal CPAP levels for the treatment of respiratory distress syndrome in preterm infants-"The OPTTIMMAL-Trial"-Optimizing PEEP To The IMMAture Lungs: study protocol of a randomized controlled trial. Waitz, M., Engel, C., Schloesser, R., et al.[2021]

A study of 278 extremely low birth weight infants across 17 neonatal centers found significant variation in the maximum end-expiratory pressure (PEEP) levels used during mechanical ventilation, ranging from 3 to 9 cm H2O, with a mean of 5.7 cm H2O.

Even after adjusting for infant characteristics that influence PEEP selection, the center of care accounted for more variation in PEEP levels than any individual infant factors, highlighting the need for standardized guidelines in respiratory care for vulnerable preterm infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Variation in Positive End-Expiratory Pressure Levels for Mechanically Ventilated Extremely Low Birth Weight Infants. Bamat, NA., Guevara, JP., Bryan, M., et al.[2019]

Positive end-expiratory pressure (PEEP) enhances gas exchange in newborns and children by increasing functional residual capacity and reducing respiratory effort, making it a crucial component in both non-invasive and invasive ventilation.

PEEP can be tailored to individual patients based on blood gas analysis and other parameters, which helps minimize lung injury and prevent circulatory failure, particularly in cases of severe respiratory failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positive end-expiratory pressure during mechanical ventilation and noninvasive respiratory support in newborns and children. Dąbrowska-Wójciak, I., Piotrowski, A.[2019]

PEEP and CPAP are effective methods for improving oxygenation in patients by increasing functional residual capacity and potentially enhancing lung compliance, which can make breathing easier.

While beneficial, the use of PEEP and CPAP can lead to complications such as pulmonary barotrauma and decreased cardiac output, highlighting the need for careful monitoring of pressure levels during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PEEP and CPAP. Duncan, AW., Oh, TE., Hillman, DR.[2022]

In a pilot study involving 51 premature neonates, the use of positive end-expiratory pressure (PEEP) during resuscitation did not show significant differences in short-term respiratory outcomes compared to no PEEP, despite some evidence suggesting potential benefits.

The study highlighted the need for larger trials to better assess the safety and efficacy of PEEP in improving respiratory outcomes for preterm infants immediately after birth, as the small sample size limited definitive conclusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positive end-expiratory pressure during resuscitation at birth in very-low birth weight infants: A randomized-controlled pilot trial. Kitsommart, R., Nakornchai, K., Yangthara, B., et al.[2019]

In a study involving 46 nursing students in Tanzania, two novel PEEP valves were successfully used to generate positive end expiratory pressure (PEEP) during simulated neonatal ventilation, achieving mean PEEP levels of 4.4 cm H2O and 4.9 cm H2O.

The use of these PEEP valves resulted in a significant increase in mean airway pressure (16.3 cm H2O) compared to ventilation without PEEP (14.2 cm H2O), suggesting that these devices could enhance neonatal resuscitation efforts in settings with limited resources.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neonatal ventilation with a manikin model and two novel PEEP valves without an external gas source. Thallinger, M., Ersdal, HL., Morley, C., et al.[2017]

References

1. Germany pubmed.ncbi.nlm.nih.gov

A novel approach using volumetric dynamic airway computed tomography to determine positive end-expiratory pressure (PEEP) settings to maintain airway patency in ventilated infants with bronchopulmonary dysplasia. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Differential Prognostic Analysis of Higher and Lower PEEP in ARDS Patients: Systematic Review and Meta-Analysis. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Effects of varying levels of positive end-expiratory pressure on intracranial pressure and cerebral perfusion pressure. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Application of two different nasal CPAP levels for the treatment of respiratory distress syndrome in preterm infants-"The OPTTIMMAL-Trial"-Optimizing PEEP To The IMMAture Lungs: study protocol of a randomized controlled trial. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Variation in Positive End-Expiratory Pressure Levels for Mechanically Ventilated Extremely Low Birth Weight Infants. [2019]

6. Poland pubmed.ncbi.nlm.nih.gov

Positive end-expiratory pressure during mechanical ventilation and noninvasive respiratory support in newborns and children. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

PEEP and CPAP. [2022]

8. Singapore pubmed.ncbi.nlm.nih.gov

Positive end-expiratory pressure during resuscitation at birth in very-low birth weight infants: A randomized-controlled pilot trial. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Neonatal ventilation with a manikin model and two novel PEEP valves without an external gas source. [2017]