Trial Outcomes & Findings for HFNC Flow Titration and Effort of Breathing in the PICU (NCT NCT02793674)

Results Overview

PRP is a validated objective metric of effort of breathing which is derived from the product of the peak-to-trough change in esophageal pressure (in cmH20) and the respiratory rate (breaths per minute). The percent change in PRP is derived from the quotient of the absolute PRP at increased HFNC flow rates (1.0, 1.5, and 2.0 L/kg/min) divided by the absolute PRP at a baseline HFNC flow rate (0.5 L/kg/min). Percent change in PRP was used because a) there was a large degree of heterogeneity in baseline absolute PRP values in our study population based upon patient size, disease severity, and time point of illness, and b) we allowed for repeated measures on the same patient which would bias absolute PRP values in favor of those who were measured more frequently. It was not pre-specified to compare the two different HFNC delivery systems.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

21 participants

Primary outcome timeframe

median percent change in PRP over 5 minute measurement period

Results posted on

2024-10-30

Participant Flow

This study screened patients admitted to the PICU during the study period (September 2014 to June 2016) who were \<3 years of age and started on high flow nasal cannula by the clinical team.

Of the 54 patients who met eligibility criteria on screening, 39% (N=21) underwent high flow nasal cannula flow titrations and had effort of breathing measurements taken.

Participant milestones

Participant milestones
Measure	Fisher & Paykel (FP) HFNC A subgroup of participants were placed exclusively on Fisher \& Paykel (FP) high flow nasal cannula (HFNC) (N=9). The flow rate of the HFNC was adjusted to determine if there existed a change in their effort of breathing (EOB) at different conditions. Measurements of effort of breathing was obtained at flow rates of 0.5, 1.0, 1.5, and 2.0 L/kg/min. Adequate time was allowed at each flow rate for stabilization of EOB and flow levels were trialed in a random order, each for approximately 5 minutes.	Vapotherm (VT) HFNC A subgroup of patients (N=12) had flow titrations performed on both Fisher \& Paykel (FP) and Vapotherm (VT) high flow nasal cannula (HFNC) delivery systems. The flow rate of the HFNC was adjusted to determine if there existed a change in their effort of breathing (EOB) at different conditions. These patients had flow titrations on both HFNC delivery systems performed to compare EOB on these two different HFNC delivery systems. With one exception, titrations were performed on FP first, then crossed over to VT. Measurements of effort of breathing was obtained at flow rates of 0.5, 1.0, 1.5, and 2.0 L/kg/min. Adequate time was allowed at each flow rate for stabilization of EOB and flow levels were trialed in a random order, each for approximately 5 minutes.
Overall Study STARTED	9	12
Overall Study COMPLETED	9	12
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

HFNC Flow Titration and Effort of Breathing in the PICU

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Fisher & Paykel (FP) HFNC n=9 Participants A subgroup was studied on Fisher \& Paykel (FP) high flow nasal cannula (HFNC) exclusively (N=9). The flow rate of the HFNC was adjusted to determine if there existed a change in their effort of breathing (EOB) at different conditions. Measurements of effort of breathing was obtained at flow rates of 0.5, 1.0, 1.5, and 2.0 L/kg/min. Adequate time was allowed at each flow rate for stabilization of EOB and flow levels were trialed in a random order, each for approximately 5 minutes.	Vapotherm (VT) HFNC n=12 Participants A subgroup was studied on Vapotherm (VT) high flow nasal cannula (HFNC) (N=12). These patients then crossed over to the other arm and had back-to-back titrations on both types of HFNC (FP and VT). The flow rate of the HFNC was adjusted to determine if there existed a change in their effort of breathing (EOB) at different conditions. Measurements of effort of breathing was obtained at flow rates of 0.5, 1.0, 1.5, and 2.0 L/kg/min. Adequate time was allowed at each flow rate for stabilization of EOB and flow levels were trialed in a random order, each for approximately 5 minutes.	Total n=21 Participants Total of all reporting groups
Age, Continuous	15 months n=5 Participants	4 months n=7 Participants	6 months n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity / Race · African-American	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity / Race · Hispanic	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity / Race · Not specified	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Weight	9 kilograms n=5 Participants	6.5 kilograms n=7 Participants	6.5 kilograms n=5 Participants
Respiratory Illness Bronchiolitis	6 participants n=5 Participants	7 participants n=7 Participants	13 participants n=5 Participants
Respiratory Illness Pneumonia	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Respiratory Illness Other	1 participants n=5 Participants	5 participants n=7 Participants	6 participants n=5 Participants

PRIMARY outcome

Timeframe: median percent change in PRP over 5 minute measurement period

Population: For this outcome measure, the arms/groups were combined to include all patients enrolled in the study. This included the patients studied on FP only (n=9) and those studied on VT and FP both (n=12) for a total n=21.

PRP is a validated objective metric of effort of breathing which is derived from the product of the peak-to-trough change in esophageal pressure (in cmH20) and the respiratory rate (breaths per minute). The percent change in PRP is derived from the quotient of the absolute PRP at increased HFNC flow rates (1.0, 1.5, and 2.0 L/kg/min) divided by the absolute PRP at a baseline HFNC flow rate (0.5 L/kg/min). Percent change in PRP was used because a) there was a large degree of heterogeneity in baseline absolute PRP values in our study population based upon patient size, disease severity, and time point of illness, and b) we allowed for repeated measures on the same patient which would bias absolute PRP values in favor of those who were measured more frequently. It was not pre-specified to compare the two different HFNC delivery systems.

Outcome measures

Outcome measures
Measure	Percent Change in Pressure-Rate Product n=21 Participants All participants in the study were placed on high flow nasal cannula (HFNC). For this outcome, the median percent change in PRP was obtained for all titrations on both types of HFNC delivery system (FP and VT). The flow rate of the HFNC was adjusted to determine if there existed a change in their effort of breathing (EOB) at different conditions. Measurements of effort of breathing was obtained at flow rates of 0.5, 1.0, 1.5, and 2.0 L/kg/min. Adequate time was allowed at each flow rate for stabilization of EOB and flow levels were trialed in a random order, each for approximately 5 minutes.	Vapotherm HFNC Delivery System This arm shows the outcome (the median of the percent change in PRP from baseline as a function of flow rate) for these patients when they were studied on the VT HFNC delivery system.
Percent Change in Pressure-rate Product (PRP) as a Function of Increasing HFNC Flow Rate on Both Types of HFNC Delivery System (FP and VT) Percent Change in PRP at 1.0 L/kg/min	-10 percent change in PRP Interval -22.0 to 0.0	—
Percent Change in Pressure-rate Product (PRP) as a Function of Increasing HFNC Flow Rate on Both Types of HFNC Delivery System (FP and VT) Percent Change in PRP at 1.5 L/kg/min	-20 percent change in PRP Interval -35.0 to -3.5	—
Percent Change in Pressure-rate Product (PRP) as a Function of Increasing HFNC Flow Rate on Both Types of HFNC Delivery System (FP and VT) Percent Change in PRP at 2.0 L/kg/min	-23 percent change in PRP Interval -33.0 to -9.0	—

SECONDARY outcome

Timeframe: median PRP over a 5 minute period

Population: For this outcome measure, the arms/groups were combined to include all patients enrolled in the study. This included the patients studied on FP only (n=9) and those studied on VT and FP both (n=12) for a total n=21.

PRP is a validated objective metric of effort of breathing which is derived from the product of the peak-to-trough change in esophageal pressure (in cmH20) and the respiratory rate (breaths per minute). These values were obtained from 5 minute flow titration periods. For this outcome, the PRP was obtained for all titrations on both types of HFNC delivery system (FP and VT). It was not pre-specified to compare the two different HFNC delivery systems.

Outcome measures

Outcome measures
Measure	Percent Change in Pressure-Rate Product n=21 Participants All participants in the study were placed on high flow nasal cannula (HFNC). For this outcome, the median percent change in PRP was obtained for all titrations on both types of HFNC delivery system (FP and VT). The flow rate of the HFNC was adjusted to determine if there existed a change in their effort of breathing (EOB) at different conditions. Measurements of effort of breathing was obtained at flow rates of 0.5, 1.0, 1.5, and 2.0 L/kg/min. Adequate time was allowed at each flow rate for stabilization of EOB and flow levels were trialed in a random order, each for approximately 5 minutes.	Vapotherm HFNC Delivery System This arm shows the outcome (the median of the percent change in PRP from baseline as a function of flow rate) for these patients when they were studied on the VT HFNC delivery system.
Pressure-rate Product (PRP) as a Function of Increasing HFNC Flow Rate on Both Types of HFNC Delivery System (FP and VT) PRP at 0.5 L/kg/min	824 cmH20 * breaths/minute Interval 592.0 to 1252.0	—
Pressure-rate Product (PRP) as a Function of Increasing HFNC Flow Rate on Both Types of HFNC Delivery System (FP and VT) PRP at 1.0 L/kg/min	699 cmH20 * breaths/minute Interval 461.0 to 1080.0	—
Pressure-rate Product (PRP) as a Function of Increasing HFNC Flow Rate on Both Types of HFNC Delivery System (FP and VT) PRP at 1.5 L/kg/min	596 cmH20 * breaths/minute Interval 406.0 to 923.0	—
Pressure-rate Product (PRP) as a Function of Increasing HFNC Flow Rate on Both Types of HFNC Delivery System (FP and VT) PRP at 2.0 L/kg/min	594 cmH20 * breaths/minute Interval 365.0 to 893.0	—

SECONDARY outcome

Timeframe: median phase angle over a 5 minute period

Population: For this outcome measure, the arms/groups were combined to include all patients enrolled in the study. This included the patients studied on FP only (n=9) and those studied on VT and FP both (n=12) for a total n=21.

Phase angle is a measure of asynchrony between thoracic and abdominal breathing compartments that has correlated with increased effort of breathing. It is derived by measuring the relative expansion of these two breathing compartments and describing the synchrony between them as an angle (theta). For this outcome, the phase angle was obtained for all titrations on both types of HFNC delivery system (FP and VT). It was not pre-specified to compare the two different HFNC delivery systems.

Outcome measures

Outcome measures
Measure	Percent Change in Pressure-Rate Product n=21 Participants All participants in the study were placed on high flow nasal cannula (HFNC). For this outcome, the median percent change in PRP was obtained for all titrations on both types of HFNC delivery system (FP and VT). The flow rate of the HFNC was adjusted to determine if there existed a change in their effort of breathing (EOB) at different conditions. Measurements of effort of breathing was obtained at flow rates of 0.5, 1.0, 1.5, and 2.0 L/kg/min. Adequate time was allowed at each flow rate for stabilization of EOB and flow levels were trialed in a random order, each for approximately 5 minutes.	Vapotherm HFNC Delivery System This arm shows the outcome (the median of the percent change in PRP from baseline as a function of flow rate) for these patients when they were studied on the VT HFNC delivery system.
Phase Angle as a Function of Increasing HFNC Flow Rate on Both Types of HFNC Delivery System (FP and VT) 0.5 L/kg/min	61 degrees Interval 40.0 to 115.0	—
Phase Angle as a Function of Increasing HFNC Flow Rate on Both Types of HFNC Delivery System (FP and VT) 1.0 L/kg/min	61 degrees Interval 38.0 to 120.0	—
Phase Angle as a Function of Increasing HFNC Flow Rate on Both Types of HFNC Delivery System (FP and VT) 1.5 L/kg/min	68 degrees Interval 38.0 to 122.0	—
Phase Angle as a Function of Increasing HFNC Flow Rate on Both Types of HFNC Delivery System (FP and VT) 2.0 L/kg/min	59 degrees Interval 34.0 to 138.0	—

SECONDARY outcome

Timeframe: median PRP over a 5 minute period

Population: Percent change in PRP from baseline (of 0.5 L/kg/min) was measured at different flow rates (1.0, 1.5, and 2.0 L/kg/min) for patients who had flow titrations done on the two different HFNC delivery systems (Fisher \& Paykel (FP) and Vapotherm (VT)).

For this outcome, a subgroup of patients (N=12) were examined who had PRP measurements obtained on two different HFNC delivery systems (Fisher \& Paykel (FP) and Vapotherm (VT)) in back-to-back flow titration periods. With one exception, patients were first studied on the FP and then transitioned to the VT HFNC delivery system.

Outcome measures

Outcome measures
Measure	Percent Change in Pressure-Rate Product n=12 Participants All participants in the study were placed on high flow nasal cannula (HFNC). For this outcome, the median percent change in PRP was obtained for all titrations on both types of HFNC delivery system (FP and VT). The flow rate of the HFNC was adjusted to determine if there existed a change in their effort of breathing (EOB) at different conditions. Measurements of effort of breathing was obtained at flow rates of 0.5, 1.0, 1.5, and 2.0 L/kg/min. Adequate time was allowed at each flow rate for stabilization of EOB and flow levels were trialed in a random order, each for approximately 5 minutes.	Vapotherm HFNC Delivery System n=12 Participants This arm shows the outcome (the median of the percent change in PRP from baseline as a function of flow rate) for these patients when they were studied on the VT HFNC delivery system.
Percent Change in Pressure-rate Product (PRP) From Baseline as a Function of Increasing HFNC Flow Rate, Comparing Different HFNC Delivery Systems 1.0 L/kg/min	-15 percent change in PRP Interval -22.0 to -5.0	-9 percent change in PRP Interval -18.0 to 4.0
Percent Change in Pressure-rate Product (PRP) From Baseline as a Function of Increasing HFNC Flow Rate, Comparing Different HFNC Delivery Systems 1.5 L/kg/min	-19 percent change in PRP Interval -42.0 to -7.0	-22 percent change in PRP Interval -30.0 to 2.0
Percent Change in Pressure-rate Product (PRP) From Baseline as a Function of Increasing HFNC Flow Rate, Comparing Different HFNC Delivery Systems 2.0 L/kg/min	-23 percent change in PRP Interval -36.0 to -17.0	-11 percent change in PRP Interval -32.0 to 8.0

SECONDARY outcome

Timeframe: medain percent change in PRP over a 5 minute period

Population: For this outcome measure, the arms/groups were combined to include all patients enrolled in the study. This included the patients studied on FP only (n=9) and those studied on VT and FP both (n=12) for a total n=21.

To assess the relationship between patient size and dose-response of HFNC flow rate, we compared subgroups stratified by weight (patients \<8 kg and \>8 kg). For this outcome, the median percent change in PRP was obtained for all titrations on both types of HFNC delivery system (FP and VT). It was not pre-specified to compare the two different HFNC delivery systems.

Outcome measures

Outcome measures
Measure	Percent Change in Pressure-Rate Product n=12 Participants All participants in the study were placed on high flow nasal cannula (HFNC). For this outcome, the median percent change in PRP was obtained for all titrations on both types of HFNC delivery system (FP and VT). The flow rate of the HFNC was adjusted to determine if there existed a change in their effort of breathing (EOB) at different conditions. Measurements of effort of breathing was obtained at flow rates of 0.5, 1.0, 1.5, and 2.0 L/kg/min. Adequate time was allowed at each flow rate for stabilization of EOB and flow levels were trialed in a random order, each for approximately 5 minutes.	Vapotherm HFNC Delivery System n=9 Participants This arm shows the outcome (the median of the percent change in PRP from baseline as a function of flow rate) for these patients when they were studied on the VT HFNC delivery system.
Percent Change in Pressure-rate Product (PRP) From Baseline as a Function of Increasing HFNC Flow Rate, Comparing Weight-Stratified Subgroups on Both Types of HFNC Delivery System (FP and VT) 1.0 L/kg/min	-14 percent change in PRP from baseline Interval -23.0 to 0.0	-5 percent change in PRP from baseline Interval -10.0 to 3.0
Percent Change in Pressure-rate Product (PRP) From Baseline as a Function of Increasing HFNC Flow Rate, Comparing Weight-Stratified Subgroups on Both Types of HFNC Delivery System (FP and VT) 1.5 L/kg/min	-27 percent change in PRP from baseline Interval -44.0 to -5.0	-2 percent change in PRP from baseline Interval -22.0 to 5.0
Percent Change in Pressure-rate Product (PRP) From Baseline as a Function of Increasing HFNC Flow Rate, Comparing Weight-Stratified Subgroups on Both Types of HFNC Delivery System (FP and VT) 2.0 L/kg/min	-25 percent change in PRP from baseline Interval -45.0 to -16.0	-15 percent change in PRP from baseline Interval -29.0 to -8.0

SECONDARY outcome

Timeframe: median of the maximum percent change in PRP over a 5 minute period

Population: For this outcome measure, the arms/groups were combined to include all patients enrolled in the study. This included the patients studied on FP only (n=9) and those studied on VT and FP both (n=12) for a total n=21.

Exploratory analysis of patients by further stratified weight groupings (\<5 kg, 5-8 kg, and \>8 kg) was performed to determine the greatest observed benefit of HFNC flow titration in patients of different sizes. For this outcome, the maximum percent change in PRP was obtained for all titrations on both types of HFNC delivery system (FP and VT). It was not pre-specified to compare the two different HFNC delivery systems.

Outcome measures

Outcome measures
Measure	Percent Change in Pressure-Rate Product n=21 Participants All participants in the study were placed on high flow nasal cannula (HFNC). For this outcome, the median percent change in PRP was obtained for all titrations on both types of HFNC delivery system (FP and VT). The flow rate of the HFNC was adjusted to determine if there existed a change in their effort of breathing (EOB) at different conditions. Measurements of effort of breathing was obtained at flow rates of 0.5, 1.0, 1.5, and 2.0 L/kg/min. Adequate time was allowed at each flow rate for stabilization of EOB and flow levels were trialed in a random order, each for approximately 5 minutes.	Vapotherm HFNC Delivery System This arm shows the outcome (the median of the percent change in PRP from baseline as a function of flow rate) for these patients when they were studied on the VT HFNC delivery system.
Maximum Percent Change in Pressure-rate Product (PRP) From Baseline as a Function of Increasing HFNC Flow Rate, Comparing Weight-Stratified Subgroups on Both Types of HFNC Delivery System (FP and VT) <5 kg	-46 percent Interval -52.0 to -29.0	—
Maximum Percent Change in Pressure-rate Product (PRP) From Baseline as a Function of Increasing HFNC Flow Rate, Comparing Weight-Stratified Subgroups on Both Types of HFNC Delivery System (FP and VT) 5-8 kg	-30 percent Interval -48.0 to -6.0	—
Maximum Percent Change in Pressure-rate Product (PRP) From Baseline as a Function of Increasing HFNC Flow Rate, Comparing Weight-Stratified Subgroups on Both Types of HFNC Delivery System (FP and VT) >8 kg	-17 percent Interval -33.0 to 6.0	—

Adverse Events

Fisher & Paykel (FP) High Flow Nasal Cannula

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Vapotherm (VT) High Flow Nasal Cannula

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Fisher & Paykel (FP) High Flow Nasal Cannula n=21 participants at risk A subgroup was studied on Fisher \& Paykel (FP) high flow nasal cannula (HFNC) exclusively (N=9). The flow rate of the HFNC was adjusted to determine if there existed a change in their effort of breathing (EOB) at different conditions.	Vapotherm (VT) High Flow Nasal Cannula n=12 participants at risk A subgroup was studied on Vapotherm (VT) high flow nasal cannula (HFNC) (N=12). These patients then crossed over to the other arm and had back-to-back titrations on both types of HFNC (FP and VT). The flow rate of the HFNC was adjusted to determine if there existed a change in their effort of breathing (EOB) at different conditions.
Product Issues any adverse event	0.00% 0/21 • 22 months	0.00% 0/12 • 22 months

Additional Information

Thomas Weiler, MD

Presbyterian Hospital

Phone: 505-724-7044

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place