Comparing Different Delivery Systems of Continuous Positive Airway Pressure in Neonates

Study Overview
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Brief Summary
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The goal of this clinical trial is to compare late preterm newborn lung physiology when supported with different continuous positive airway pressure (CPAP) devices. The main questions it aims to answer are: Which CPAP modality provides better breathing support in newborns with respiratory distress syndrome who are greater than 32 weeks gestational age? Does the lung physiology data predict the CPAP modality that will result in a shorter CPAP treatment duration? Participants will wear a belt of electrodes on their chest (electrical impedance tomography) and have an esophageal balloon manometry measure lung physiology data for 2.5 hours while switching CPAP devices. Participants will then be randomly assigned to a CPAP device to support their breathing until they recover from respiratory distress syndrome.

Detailed Description
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Across centers, there is a variation in standard of care for the preferred device and interface to deliver continuous positive airway pressure (CPAP) to support neonatal functional residual capacity. CPAP, a type of noninvasive respiratory support, is commonly delivered to neonates by mechanical ventilators or underwater bubble devices (bubble CPAP). Variation also exists with the tubing used to deliver CPAP. One commonly used nasal interface is the RAM cannula (Neotech, Valencia, CA), made of a soft material with thin tubing walls and is designed to provide 60-80% occlusion of the nares. This contrasts with the occlusive interface intended to provide complete seal. To provide evidence for standardization of CPAP delivery, clinical trials are needed to assess which modality of CPAP delivery is optimal for neonates with respiratory distress syndrome who are > 32 weeks and <37 weeks gestational age, an understudied population. The investigators propose to use electrical impedance tomography (EIT) paired with esophageal balloon manometry to assess neonatal lung physiology when supported with different modalities of CPAP. Furthermore, participants will be randomly assigned to A) physiology based CPAP vs B) one size fits all approach. The subjects will remain on the assigned modality of CPAP for the remainder of their respiratory distress syndrome treatment, and researchers will track which modality of CPAP results in a shorter CPAP treatment period and if this is expected based on the lung physiology data collected.

Official Title
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Comparing Regional Ventilation in Neonates With Different Delivery Systems of Continuous Positive Airway Pressure

Conditions
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Prematurity, Respiratory Distress Syndrome

Intervention / Treatment
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* Device: RAM cannula ventilator CPAP
* Device: Occlusive interface bubble CPAP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: medically stable neonates born >32 0/7 weeks and < 37 0/7 weeks gestational age, with birth weights > 1500 grams, are chronologically 12-36 hours old, and are receiving RAM cannula ventilator CPAP with positive end expiratory pressure (PEEP) between 5-6 cm water (H2O) and Fraction of inspired oxygen (FiO2) < 0.3 for the suspected diagnosis of respiratory distress syndrome Exclusion Criteria: neonates with congenital anomalies that potentially will affect respiratory physiology, for example hypoplastic lungs or gastroschisis. neonates with contraindications for wearing an occlusive interface, for example epidermolysis bullosa which may have risk of worsening skin integrity at the pressure points of the occlusive interface, or a known small air leak that may potentially develop into a large pneumothorax. neonates with contraindications for placement of esophageal balloon manometry, for example hypoglycemia managed with extended feeding times greater than 30 minutes. neonates with contraindications for electrical impedance tomography, for example inability to ensure contact of the electrodes on the belt with the skin on the circumference of the chest due to presence of a chest tube dressing.

Ages Eligible for Study
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Minimum Age: 12 Hours
Maximum Age: 36 Hours

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Lung physiology measurements with electrical impedance tomography and esophageal manometry will be collected while the participant is supported with RAM cannula ventilator CPAP followed by occlusive interface ventilator CPAP followed by occlusive interface bubble CPAP. A 1:1 block randomization of either A) physiology-based CPAP or B) one size fits all CPAP of either RAM cannula ventilator CPAP or occlusive interface bubble CPAP will be assigned to the participant. Arm B is further randomized 1:1 to either RAM cannula ventilator CPAP or occlusive interface bubble CPAP. The duration of CPAP treatment will be compared between the two arms (precision medicine approach vs standard of care) as well as compare each device and whether the physiology data would have predicted the CPAP device would have resulted in a shorter treatment period.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Randomization to CPAP with higher change of impedance as measured by EIT. Arm A-1<br>After comparing change of impedance as measured by electrical impedance tomography while supported on RAM cannula ventilator CPAP versus occlusive interface bubble CPAP, the participants in this arm are placed on the CPAP that had a greater change of impedance (or less pressure rate product as measured by the esophageal balloon manometry if the change of impedance between the two CPAP modalities are clinically similar). In this Arm A-1, these subjects had higher change in impedance while supported on RAM cannula ventilator CPAP | Device: RAM cannula ventilator CPAP<br>* RAM cannula ventilator CPAP<br>|
| Experimental: Randomization to CPAP with higher change of impedance as measured by EIT. Arm A-2<br>After comparing change of impedance as measured by electrical impedance tomography while supported on RAM cannula ventilator CPAP versus occlusive interface bubble CPAP, the participants in this arm are placed on the CPAP that had a greater change of impedance (or less pressure rate product as measured by the esophageal balloon manometry if the change of impedance between the two CPAP modalities are clinically similar). In this Arm A-2, these subjects had higher change in impedance while supported on occlusive mask bubble CPAP | Device: Occlusive interface bubble CPAP<br>* Occlusive interface bubble CPAP<br>|
| Active Comparator: Randomization to standard of care - a 'one size fits all' approach. Arm B-1<br>Currently, the approach to which CPAP modality is chosen for these newborns is defaulted to the preferred CPAP of the Neonatal Intensive Care Unit (NICU) where the newborn is hospitalized. In this Arm B-1, these subjects are randomized 1:1 to RAM cannula ventilator CPAP | Device: RAM cannula ventilator CPAP<br>* RAM cannula ventilator CPAP<br>|
| Active Comparator: Randomization to standard of care - a 'one size fits all' approach. Arm B-2<br>Currently, the approach to which CPAP modality is chosen for these newborns is defaulted to the preferred CPAP of the NICU where the newborn is hospitalized. In this Arm B-2, these subjects are randomized 1:1 to occlusive mask bubble CPAP | Device: Occlusive interface bubble CPAP<br>* Occlusive interface bubble CPAP<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in electrical impedance | change in average electrical impedance with each CPAP delivery modality | 2.5 hours during the lung physiology assessment | 
| duration of CPAP treatment | compare groups Arm A-1, A-2 vs Arm B-1, B2; Compare groups Arm A-1, B-1 vs Arm A-2, B-2 | through study completion, an average of 2 weeks after the lung physiology assessment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| lung physiology measurements (exploratory measures during this pilot study, in preparation for a powered larger trial) change in end expiratory lung impedance | change in end expiratory lung impedance (arbitrary units) | 2.5 hours during the lung physiology assessment | 
| lung physiology measurements (exploratory measures during this pilot study, in preparation for a powered larger trial) vascular pulsatility | vascular pulsatility (arbitrary units) | 2.5 hours during the lung physiology assessment | 
| lung physiology measurements (exploratory measures during this pilot study, in preparation for a powered larger trial) tidal volume | tidal volume (in milliliters) per weight (in kilograms) | 2.5 hours during the lung physiology assessment | 
| lung physiology measurements (exploratory measures during this pilot study, in preparation for a powered larger trial) change in minute ventilation | change in minute ventilation (mL/minute) | 2.5 hours during the lung physiology assessment | 
| lung physiology measurements (exploratory measures during this pilot study, in preparation for a powered larger trial) change in dynamic compliance | change in dynamic compliance (mL/cmH2O) | 2.5 hours during the lung physiology assessment | 
| lung physiology measurements (exploratory measures during this pilot study, in preparation for a powered larger trial) Respiratory rate | Respiratory rate (breaths per minute) | 2.5 hours during the lung physiology assessment | 
| lung physiology measurements (exploratory measures during this pilot study, in preparation for a powered larger trial) Oxygen saturation | Oxygen saturation (percentage) | 2.5 hours during the lung physiology assessment | 
| lung physiology measurements (exploratory measures during this pilot study, in preparation for a powered larger trial) Abdominal circumference | Abdominal circumference (cm) | 2.5 hours during the lung physiology assessment | 
| lung physiology measurements (exploratory measures during this pilot study, in preparation for a powered larger trial) esophageal pressure change | esophageal pressure change (mm Hg) | 2.5 hours during the lung physiology assessment | 
| lung physiology measurements (exploratory measures during this pilot study, in preparation for a powered larger trial) end expiratory pressure | end expiratory pressure via esophageal balloon manometry (mm Hg) | 2.5 hours during the lung physiology assessment | 
| lung physiology measurements (exploratory measures during this pilot study, in preparation for a powered larger trial) pressure rate product | pressure rate product (cm H2O / min) | 2.5 hours during the lung physiology assessment | 
| clinical outcomes of different CPAP modalities (exploratory measures during this pilot study, in preparation for a powered larger trial) Frequency of deviation | frequency of deviation from assigned CPAP treatment (percentage) | through study completion, an average of 2 weeks after the lung physiology assessment | 
| clinical outcomes of different CPAP modalities (exploratory measures during this pilot study, in preparation for a powered larger trial) frequency of exogenous surfactant administration | frequency of exogenous surfactant administration (percentage) | through study completion, an average of 2 weeks after the lung physiology assessment | 
| clinical outcomes of different CPAP modalities (exploratory measures during this pilot study, in preparation for a powered larger trial) | respiratory support settings if deviated from assigned CPAP treatment (percentage) | through study completion, an average of 2 weeks after the lung physiology assessment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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continuous positive airway pressure