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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the best way to help very premature babies breathe right after birth using positive end-expiratory pressure (PEEP), a type of respiratory support. It compares two approaches: providing a steady level of PEEP or starting with a high level and then lowering it. The goal is to determine which method reduces the overall need for breathing support. This trial targets babies born very early, between 23 and 28 weeks, who require breathing assistance immediately after birth. As an unphased trial, it offers a unique opportunity to contribute to important research that could enhance breathing support for very premature babies.

Will I have to stop taking my current medications?

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

What prior data suggests that these PEEP methods are safe for premature babies?

Research has shown that Positive End-Expiratory Pressure (PEEP) is generally safe for newborns, including premature babies. PEEP keeps their lungs open by gently blowing air into them between breaths. Studies have found that PEEP effectively supports breathing in premature infants and is a simple, practical, and affordable treatment.

However, while PEEP is widely used, it can sometimes cause side effects, such as lung injury or affecting heart function. Despite these possible risks, PEEP remains common in newborn care due to its overall benefits.

For the specific PEEP methods under study—dynamic and static PEEP—evidence suggests both are safely used in medical settings. Dynamic PEEP adjusts air pressure based on the baby's needs and has been studied for its potential to reduce lung injury. Static PEEP maintains a steady pressure and is also commonly used.

In summary, while some risks exist, PEEP is generally well-tolerated and is a standard treatment to help premature babies breathe at birth. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about exploring different PEEP levels for premature birth because they aim to optimize respiratory support for these vulnerable infants. Unlike the standard practice of using a fixed PEEP level, this study tests dynamic PEEP adjustments, which adapt to the infant's changing needs. The Dynamic PEEP Group uses variable pressure levels, starting at 8 cmH2O and increasing as needed, which is hoped to improve oxygenation more effectively than static approaches. This method could lead to better outcomes by providing more personalized and responsive care during critical early life stages.

What evidence suggests that this trial's PEEP methods could be effective for premature babies?

This trial will compare two approaches to PEEP in premature babies: a Dynamic PEEP Group and a Static PEEP Group. Studies have shown that a flexible approach to PEEP, like the Dynamic PEEP Group in this trial, where the pressure adjusts based on the baby's needs, may improve breathing in premature babies. Research suggests that this method can lead to better stability during resuscitation and may reduce the need for intubation. Other studies on newborn lambs demonstrated that higher PEEP levels at birth can improve lung function and reduce damage. However, the best PEEP level to use immediately after birth is still under investigation, and more evidence is needed to determine the most effective approach. Dynamic PEEP is considered promising because it adapts to the baby's condition, potentially lowering the risk of long-term lung problems. ^{1 2 3 6 7}

Who Is on the Research Team?

David Tingay, MBBS FRACP

Principal Investigator

Royal Children's Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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]

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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9874145/

Individualized dynamic PEEP (dynPEEP) vs. positive ...

Primary outcomes included the DR intubation rate and the bronchopulmonary dysplasia (BPD) rate. The secondary outcomes included DR stabilization ...

2.

journals.physiology.org

journals.physiology.org/doi/abs/10.1152/ajplung.00047.2022

Dynamic positive end-expiratory pressure strategies using ...

The objective of this study was to determine the effect of maximum PEEP levels at birth on the physiological and injury response in preterm lambs.

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04372953

NCT04372953 | Positive End-Expiratory Pressure (PEEP) ...

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 ...

4.

centerwatch.com

centerwatch.com/clinical-trials/listings/NCT04372953/positive-end-expiratory-pressure-peep-levels-during-resuscitation-of-preterm-infants-at-birth-the-polar-trial

Positive End-Expiratory Pressure (PEEP) Levels During ...

The effective and safe level of PEEP to use after preterm birth remains the most important unanswered question in neonatal respiratory medicine.

5.

karger.com

karger.com/neo/article/121/3/288/896534/Positive-Pressure-Ventilation-in-Preterm-Infants

Positive Pressure Ventilation in Preterm Infants in the ...

A major proportion of preterm neonates require positive pressure ventilation (PPV) immediately after delivery. PPV may be administered through a face mask (FM) ...

6.

atsjournals.org

atsjournals.org/doi/full/10.1164/rccm.202301-0104OC

American Journal of Respiratory and Critical Care Medicine

Dynamic PEEP without any tidal inflations resulted in the least lung injury. Use of any tidal inflating pressures altered metabolic, coagulation ...

7.

withpower.com

withpower.com/trial/phase-lung-injury-4-2021-c2184

PEEP Levels for Premature Birth (POLAR Trial)

PEEP is generally used safely in newborns, infants, and children to help with breathing, but it can have complications like lung damage, decreased heart ...