Trial Outcomes & Findings for Physiological Changes With High-Flow Nasal Cannula (NCT NCT03700606)

Last Updated: 2026-04-17

Results Overview

Atelectasis will be calculated using the percentage of the lung fields that are not engaged in tidal volume.(VT) In Period 1 (nCPAP Baseline), infants on nCPAP at 5-7 cmH₂O in the supine position underwent up to 15 minutes of quiet-breathing EIT recording. In Period 2 (30 min on HFNC), infants were transitioned to HFNC at 8 L/min, and if tolerated, up to 15 minutes of EIT were collected at \~30 minutes. In Period 3 (6 hr on HFNC or earlier if failure), infants who tolerated HFNC underwent EIT at 6 hours; those meeting failure criteria returned immediately to nCPAP and were analyzed as Period 3 without a 6-hour EIT. In Period 4 (60 min after return to nCPAP), infants resumed nCPAP and up to 15 minutes of EIT were obtained about 60 minutes later. In period 4 one participant had missing primary outcome data and were analyzed as Period 4 without a 60 min return to nCPAP EIT measurement.

Recruitment status

COMPLETED

Study phase

Target enrollment

80 participants

Primary outcome timeframe

Primary outcome was measured during each study period: baseline on nCPAP, 30 minutes after starting HFNC, at 6 hours on HFNC or earlier if failure, and 60 minutes after returning to nCPAP.

Results posted on

2026-04-17

Participant Flow

Preterm infants born between 23 and 28+6 weeks' gestation were recruited from the Neonatal Intensive Care Unit. Infants were screened for eligibility based on respiratory stability on nCPAP, postmenstrual age ≤30 weeks, tolerance of routine handling, appropriate HFNC interface sizing, and recent stable blood gas. A total of eighty infants were enrolled in the study between March 2019 and December 2021, and written informed consent was obtained from parents or legal guardians before participation

Two participants experienced unexpected data loss prior to analysis and were excluded from all study periods. During Period 3, 20 participants were unable to complete the planned 6-hour EIT assessment following transition to HFNC. Per protocol, these participants required immediate transition back to CPAP, precluding collection of the 6-hour time-point data. EIT data were obtained for all participants after re-establishing CPAP support for 60-minutes and included in the results.

Participant milestones

Participant milestones
Measure	Participants in HFNC Trial Participants were preterm infants born at \<29 weeks' gestation who were clinically stable on nasal continuous positive airway pressure (nCPAP) at 5-7 cmH₂O. Each infant underwent a crossover sequence of respiratory support modes. Baseline measurements were obtained on nCPAP (Period 1). Infants were then transitioned to high-flow nasal cannula (HFNC) at 8 L/min, with measurements collected at 30 minutes (Period 2). Infants who tolerated HFNC remained on HFNC for 6 hours for the next assessment, while those meeting predefined failure criteria were returned immediately to nCPAP and analyzed as Period 3 without a 6-hour HFNC measurement (Period 3). All infants were then returned to nCPAP, and measurements were collected approximately 60 minutes after resumption of support (Period 4).
Baseline Measurement (CPAP) STARTED	80
Baseline Measurement (CPAP) COMPLETED	78
Baseline Measurement (CPAP) NOT COMPLETED	2
30 min post HFNC start STARTED	78
30 min post HFNC start COMPLETED	78
30 min post HFNC start NOT COMPLETED	0
6 hours after initial transition to HFNC STARTED	78
6 hours after initial transition to HFNC COMPLETED	78
6 hours after initial transition to HFNC NOT COMPLETED	0
Period 4: Stabilization on CPAP STARTED	78
Period 4: Stabilization on CPAP COMPLETED	78
Period 4: Stabilization on CPAP NOT COMPLETED	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Participants in HFNC Trial Participants were preterm infants born at \<29 weeks' gestation who were clinically stable on nasal continuous positive airway pressure (nCPAP) at 5-7 cmH₂O. Each infant underwent a crossover sequence of respiratory support modes. Baseline measurements were obtained on nCPAP (Period 1). Infants were then transitioned to high-flow nasal cannula (HFNC) at 8 L/min, with measurements collected at 30 minutes (Period 2). Infants who tolerated HFNC remained on HFNC for 6 hours for the next assessment, while those meeting predefined failure criteria were returned immediately to nCPAP and analyzed as Period 3 without a 6-hour HFNC measurement (Period 3). All infants were then returned to nCPAP, and measurements were collected approximately 60 minutes after resumption of support (Period 4).
Baseline Measurement (CPAP) data loss	2

Baseline Characteristics

Physiological Changes With High-Flow Nasal Cannula

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Participants in HFNC Trial n=78 Participants Participants were preterm infants born at \<29 weeks' gestation who were clinically stable on nasal continuous positive airway pressure (nCPAP) at 5-7 cmH₂O. Each infant underwent a crossover sequence of respiratory support modes. Baseline measurements were obtained on nCPAP (Period 1). Infants were then transitioned to high-flow nasal cannula (HFNC) at 8 L/min, with measurements collected at 30 minutes (Period 2). Infants who tolerated HFNC remained on HFNC for 6 hours for the next assessment, while those meeting predefined failure criteria were returned immediately to nCPAP and analyzed as Period 3 without a 6-hour HFNC measurement (Period 3). All infants were then returned to nCPAP, and measurements were collected approximately 60 minutes after resumption of support (Period 4).
Age, Continuous	27 weeks n=130 Participants
Sex: Female, Male Female	40 Participants n=130 Participants
Sex: Female, Male Male	38 Participants n=130 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=130 Participants
Race (NIH/OMB) Asian	6 Participants n=130 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=130 Participants
Race (NIH/OMB) Black or African American	7 Participants n=130 Participants
Race (NIH/OMB) White	24 Participants n=130 Participants
Race (NIH/OMB) More than one race	6 Participants n=130 Participants
Race (NIH/OMB) Unknown or Not Reported	35 Participants n=130 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	45 Participants n=130 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	33 Participants n=130 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=130 Participants
Region of Enrollment United States	78 Participants n=130 Participants
Postmenstrual age at the time of study enrollment	29 weeks n=130 Participants
Infant's weight at time of study enrollment	1015 grams n=130 Participants
Infant intubated any time prior to study enrollment	55 participant n=130 Participants
FiO2 settings prior to study enrollment	21 percent (%) of inspired oxygen n=130 Participants

PRIMARY outcome

Timeframe: Primary outcome was measured during each study period: baseline on nCPAP, 30 minutes after starting HFNC, at 6 hours on HFNC or earlier if failure, and 60 minutes after returning to nCPAP.

Population: In Period 3, twenty infants who met predefined HFNC failure criteria were returned immediately to nCPAP and therefore did not complete the scheduled 6-hour HFNC EIT assessment. All remaining participants contributed Period 3 data as available. In Period 4, EIT was collected for nearly all infants, although one participant had missing primary outcome data for percent of unventilated lung.

Outcome measures

Outcome measures
Measure	Participants in HFNC Trial n=78 Participants Lung function was assessed using electrical impedance tomography at four stages: baseline before any respiratory support changes, 30 minutes after transitioning from continuous positive airway pressure to high-flow nasal cannula, 6 hours after the transition (or at intolerance if high-flow nasal cannula was not tolerated), and 30 minutes after returning to continuous positive airway pressure.
Percent of Unventilated Lung as Assessed by Electrical Impedance Tomography Period 1	2.18 Percent of unventilated lung regions Standard Deviation 0.33
Percent of Unventilated Lung as Assessed by Electrical Impedance Tomography Period 2	2.32 Percent of unventilated lung regions Standard Deviation 0.33
Percent of Unventilated Lung as Assessed by Electrical Impedance Tomography Period 3	1.72 Percent of unventilated lung regions Standard Deviation 0.35
Percent of Unventilated Lung as Assessed by Electrical Impedance Tomography Period 4	2.17 Percent of unventilated lung regions Standard Deviation 0.33

SECONDARY outcome

Timeframe: This secondary outcome was measured during each study period: baseline on nCPAP, 30 minutes after starting HFNC, at 6 hours on HFNC or earlier if failure, and 60 minutes after returning to nCPAP.

Population: In Period 3, twenty infants who met predefined HFNC failure criteria were returned immediately to nCPAP and therefore did not complete the scheduled 6-hour HFNC EIT assessment. All remaining participants contributed Period 3 data as available. In Period 4, EIT measurement of Spatial center of tidal volume distribution in the thorax during ventilation was successfully collected for all participants.

Spatial center of tidal volume distribution in the thorax during ventilation

Outcome measures

Outcome measures
Measure	Participants in HFNC Trial n=78 Participants Lung function was assessed using electrical impedance tomography at four stages: baseline before any respiratory support changes, 30 minutes after transitioning from continuous positive airway pressure to high-flow nasal cannula, 6 hours after the transition (or at intolerance if high-flow nasal cannula was not tolerated), and 30 minutes after returning to continuous positive airway pressure.
Geometric Center of Ventilation (CoV) - Ventral Dorsal Period 4	60.01 Percent of ventilation distribution Standard Deviation 0.32
Geometric Center of Ventilation (CoV) - Ventral Dorsal Period 1	60.76 Percent of ventilation distribution Standard Deviation 0.31
Geometric Center of Ventilation (CoV) - Ventral Dorsal Period 2	59.98 Percent of ventilation distribution Standard Deviation 0.31
Geometric Center of Ventilation (CoV) - Ventral Dorsal Period 3	60.19 Percent of ventilation distribution Standard Deviation 0.34

SECONDARY outcome

Population: In Period 3, twenty infants who met predefined HFNC failure criteria were returned immediately to nCPAP and therefore did not complete the scheduled 6-hour HFNC EIT assessment. All remaining participants contributed Period 3 data as available. In Period 1,2, 4, EIT measurement of end-expiratory lung impedance were collected for all infants.

End-expiratory lung impedance was measured using electrical impedance tomography (EIT) to assess changes in end-expiratory lung volume. EELI reflects the sum of impedance values across all ventilated lung pixels at the end of expiration and provides an estimate of lung aeration. Values were derived from artifact-free tidal breaths captured during quiet breathing using the neonatal EIT belt and LuMon EIT system.

Outcome measures

Outcome measures
Measure	Participants in HFNC Trial n=78 Participants Lung function was assessed using electrical impedance tomography at four stages: baseline before any respiratory support changes, 30 minutes after transitioning from continuous positive airway pressure to high-flow nasal cannula, 6 hours after the transition (or at intolerance if high-flow nasal cannula was not tolerated), and 30 minutes after returning to continuous positive airway pressure.
End-expiratory Lung Impedance Period 1	9.68 Lung aeration (arbitrary units) Standard Deviation 0.39
End-expiratory Lung Impedance Period 2	9.45 Lung aeration (arbitrary units) Standard Deviation 0.39
End-expiratory Lung Impedance Period 3	10.12 Lung aeration (arbitrary units) Standard Deviation 0.42
End-expiratory Lung Impedance Period 4	9.7 Lung aeration (arbitrary units) Standard Deviation 0.39

SECONDARY outcome

Population: In Period 3, twenty infants who met predefined HFNC failure criteria were returned immediately to nCPAP and therefore did not complete the scheduled 6-hour HFNC EIT assessment. All remaining participants contributed Period 3 data as available. In Period 1,2, and 4, EIT measurement of relative tidal stretch were collected for all infants.

Measurement of how much stretch the lung tissue undergoes during inspiration relative to baseline impedance

Outcome measures

Outcome measures
Measure	Participants in HFNC Trial n=78 Participants Lung function was assessed using electrical impedance tomography at four stages: baseline before any respiratory support changes, 30 minutes after transitioning from continuous positive airway pressure to high-flow nasal cannula, 6 hours after the transition (or at intolerance if high-flow nasal cannula was not tolerated), and 30 minutes after returning to continuous positive airway pressure.
Relative Tidal Stetch Period 1	0.61 Percent of maximum impedance change Standard Deviation 0.005
Relative Tidal Stetch Period 2	0.62 Percent of maximum impedance change Standard Deviation 0.006
Relative Tidal Stetch Period 3	0.61 Percent of maximum impedance change Standard Deviation 0.006
Relative Tidal Stetch Period 4	0.60 Percent of maximum impedance change Standard Deviation 0.005

SECONDARY outcome

Timeframe: Study Period 1 through 4

Population: In Period 3, twenty infants who met predefined HFNC failure criteria were returned immediately to nCPAP and therefore did not complete the scheduled 6-hour HFNC EIT assessment. All remaining participants contributed Period 3 data as available. In Period 1,2, and 4, EIT measurement of oxygen ratio were collected for all infants.

Values \<+3 → poor oxygenation relative to ventilation (inefficient V/Q matching) Values 4-6 → moderate efficiency Values \>6 → good oxygenation efficiency relative to ventilation

Outcome measures

Outcome measures
Measure	Participants in HFNC Trial n=78 Participants Lung function was assessed using electrical impedance tomography at four stages: baseline before any respiratory support changes, 30 minutes after transitioning from continuous positive airway pressure to high-flow nasal cannula, 6 hours after the transition (or at intolerance if high-flow nasal cannula was not tolerated), and 30 minutes after returning to continuous positive airway pressure.
Oxygenation Ratio Period 1	4.12 Ratio of SpO₂ to FiO₂ (unitless) Standard Deviation 0.08
Oxygenation Ratio Period 2	3.96 Ratio of SpO₂ to FiO₂ (unitless) Standard Deviation 0.08
Oxygenation Ratio Period 3	3.99 Ratio of SpO₂ to FiO₂ (unitless) Standard Deviation 0.09
Oxygenation Ratio Period 4	4.07 Ratio of SpO₂ to FiO₂ (unitless) Standard Deviation 0.08

Adverse Events

Participants in HFNC Trial

Serious events: 0 serious events

Other events: 48 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Participants in HFNC Trial n=80 participants at risk Participants were preterm infants born at \<29 weeks' gestation who were clinically stable on nasal continuous positive airway pressure (nCPAP) at 5-7 cmH₂O. Each infant underwent a crossover sequence of respiratory support modes. Baseline measurements were obtained on nCPAP (Period 1). Infants were then transitioned to high-flow nasal cannula (HFNC) at 8 L/min, with measurements collected at 30 minutes (Period 2). Infants who tolerated HFNC remained on HFNC for 6 hours for the next assessment, while those meeting predefined failure criteria were returned immediately to nCPAP and analyzed as Period 3 without a 6-hour HFNC measurement (Period 3). All infants were then returned to nCPAP, and measurements were collected approximately 60 minutes after resumption of support (Period 4).
General disorders Intraventricular Hemorrhage	3.8% 3/80 • Adverse events were collected from enrollment through the end of the infant's hospital admission, up to 6 months of corrected gestational age. Adverse events are reported for the overall study population only, as all participants underwent the same study procedures in a crossover design and there were no differences in exposure between arms.
General disorders Periventricular Leukomalacia	0.00% 0/80 • Adverse events were collected from enrollment through the end of the infant's hospital admission, up to 6 months of corrected gestational age. Adverse events are reported for the overall study population only, as all participants underwent the same study procedures in a crossover design and there were no differences in exposure between arms.
General disorders Sepsis	7.5% 6/80 • Adverse events were collected from enrollment through the end of the infant's hospital admission, up to 6 months of corrected gestational age. Adverse events are reported for the overall study population only, as all participants underwent the same study procedures in a crossover design and there were no differences in exposure between arms.
Respiratory, thoracic and mediastinal disorders Diagnosed Chronic Lung Disease	32.5% 26/80 • Adverse events were collected from enrollment through the end of the infant's hospital admission, up to 6 months of corrected gestational age. Adverse events are reported for the overall study population only, as all participants underwent the same study procedures in a crossover design and there were no differences in exposure between arms.
Gastrointestinal disorders Diagnosed Necrotizing Enterocolitis	6.2% 5/80 • Adverse events were collected from enrollment through the end of the infant's hospital admission, up to 6 months of corrected gestational age. Adverse events are reported for the overall study population only, as all participants underwent the same study procedures in a crossover design and there were no differences in exposure between arms.
Cardiac disorders Diagnosed Patent Ductus Arteriosus and required treatment	42.5% 34/80 • Adverse events were collected from enrollment through the end of the infant's hospital admission, up to 6 months of corrected gestational age. Adverse events are reported for the overall study population only, as all participants underwent the same study procedures in a crossover design and there were no differences in exposure between arms.
Gastrointestinal disorders Diagnosed Spontaneous Intestinal Perforation	2.5% 2/80 • Adverse events were collected from enrollment through the end of the infant's hospital admission, up to 6 months of corrected gestational age. Adverse events are reported for the overall study population only, as all participants underwent the same study procedures in a crossover design and there were no differences in exposure between arms.

Additional Information

Dr. Anup Katheria

Sharp Health Care: Neonatal Research Institute

Phone: 8589394170

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place