Trial Outcomes & Findings for Comparison of CPAP Machines With Reusable vs Disposable Circuits (NCT NCT03121612)

Results Overview

Fraction of inspired oxygen (FiO2), measured as a change from baseline as shown on the two machines. Note. Outcome contaminated. An SpO2 target of 90-95% reflects currently recommended practice for neonates; when SpO2 exceeds the target, FiO2 should be reduced. The majority of readings were at SpO2 \> 95%, so FiO2 for these SpO2 readings reflects oxygen provided, not oxygen required to achieve the recommended SpO2 target range (i.e., the FiO2 provided was excessive, by an unknown amount).

Recruitment status

TERMINATED

Study phase

NA

Target enrollment

51 participants

Primary outcome timeframe

6, 12, 24, 48 and 72 hours after treatment commencement

Results posted on

2019-11-20

Participant Flow

There were no wash-out or run-in procedures. No enrolled participant was excluded from the study before randomisation.

Participant milestones

Participant milestones
Measure	Dolphin Continuous Positive Airway Pressure Continuous Positive Airway Pressure (CPAP) machine with oxygen intake and an on-board air compressor, and integrated blender and humidifier, delivering heated humidified blended gases through a Fisher-Paykel nasal mask. \[Also includes built-in Massimo pulse oximeter, though this is not used for this study, to prevent differential measurement error in SpO2 measurement\] CPAP: CPAP therapy	Fisher-Paykel Continuous Positive Airway Pressure Fisher-Paykel (F\&P) Continuous Positive Airway Pressure (CPAP) machine with separate oxygen and medical air intakes, with third-party FP-compliant blender, and F\&P blender, delivering heated humidified blended gases through a Fisher-Paykel nasal mask. CPAP: CPAP therapy
Overall Study STARTED	26	25
Overall Study COMPLETED	26	25
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dolphin Continuous Positive Airway Pressure n=26 Participants Continuous Positive Airway Pressure (CPAP) machine with oxygen intake and an on-board air compressor, and integrated blender and humidifier, delivering heated humidified blended gases through a Fisher-Paykel nasal mask. \[Also includes built-in Massimo pulse oximeter, though this is not used for this study, to prevent differential measurement error in SpO2 measurement\] CPAP: CPAP therapy	Fisher-Paykel Continuous Positive Airway Pressure n=25 Participants Fisher-Paykel (F\&P) Continuous Positive Airway Pressure (CPAP) machine with separate oxygen and medical air intakes, with third-party FP-compliant blender, and F\&P blender, delivering heated humidified blended gases through a Fisher-Paykel nasal mask. CPAP: CPAP therapy	Total n=51 Participants Total of all reporting groups
Age, Customized Gestational age	31.86 Weeks n=26 Participants	31.57 Weeks n=25 Participants	31.71 Weeks n=51 Participants
Sex: Female, Male Female	8 Participants n=26 Participants	9 Participants n=25 Participants	17 Participants n=51 Participants
Sex: Female, Male Male	18 Participants n=26 Participants	16 Participants n=25 Participants	34 Participants n=51 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment India	25 Participants n=26 Participants	26 Participants n=25 Participants	51 Participants n=51 Participants
Birthweight	1409 Grams STANDARD_DEVIATION 311 • n=26 Participants	1434 Grams STANDARD_DEVIATION 417 • n=25 Participants	1421 Grams STANDARD_DEVIATION 363 • n=51 Participants
FiO2 at baseline	40 Percentage of inspired oxygen n=26 Participants	40 Percentage of inspired oxygen n=25 Participants	40 Percentage of inspired oxygen n=51 Participants
SpO2 at baseline	96 Percentage capillary oxygen saturation n=26 Participants	97 Percentage capillary oxygen saturation n=25 Participants	97 Percentage capillary oxygen saturation n=51 Participants
Respiratory rate at baseline	42.5 Breaths/minute n=26 Participants	43 Breaths/minute n=25 Participants	43 Breaths/minute n=51 Participants
pH at baseline	7.29 pH n=19 Participants • Only 31/51 infants had a blood gas at baseline	7.34 pH n=12 Participants • Only 31/51 infants had a blood gas at baseline	7.29 pH n=31 Participants • Only 31/51 infants had a blood gas at baseline
Partial pressure of arterial oxygen at baseline	115 Torr n=19 Participants • Only 31/51 infants had a blood gas at baseline	139 Torr n=12 Participants • Only 31/51 infants had a blood gas at baseline	115 Torr n=31 Participants • Only 31/51 infants had a blood gas at baseline
Partial pressure of arterial carbon dioxide at baseline	38.9 Torr n=19 Participants • Only 31/51 infants had a blood gas at baseline	27.5 Torr n=12 Participants • Only 31/51 infants had a blood gas at baseline	37.2 Torr n=31 Participants • Only 31/51 infants had a blood gas at baseline

PRIMARY outcome

Timeframe: 6, 12, 24, 48 and 72 hours after treatment commencement

Population: Number missing at each time point: 6 hrs: 1 Dolphin (failed), 0 FP 12 hrs: 1 Dolphin (failed), 1 FP (recovered) 24 hrs: 6 Dolphin (2 failed + 4 recovered), 4 FP (all recovered) 48 hrs: 16 Dolphin (3 failed + 13 recovered), 11 FP (1 failed + 10 recovered) 72 hrs: 21 Dolphin (3 failed + 18 recovered), 21 FP (1 failed + 20 recovered)

Fraction of inspired oxygen (FiO2), measured as a change from baseline as shown on the two machines. Note. Outcome contaminated. An SpO2 target of 90-95% reflects currently recommended practice for neonates; when SpO2 exceeds the target, FiO2 should be reduced. The majority of readings were at SpO2 \> 95%, so FiO2 for these SpO2 readings reflects oxygen provided, not oxygen required to achieve the recommended SpO2 target range (i.e., the FiO2 provided was excessive, by an unknown amount).

Outcome measures

Outcome measures
Measure	Dolphin CPAP n=26 Participants CPAP machine with oxygen intake and an on-board air compressor, and integrated blender and humidifier, delivering heated humidified blended gases through a Fisher-Paykel nasal mask. \[Also includes built-in Massimo pulse oximeter, though this is not used for this study, to prevent differential measurement error in SpO2 measurement\] CPAP: CPAP therapy	Fisher-Paykel CPAP n=25 Participants Fisher-Paykel (F\&P) CPAP machine with separate oxygen and medical air intakes, with third-party FP-compliant blender, and F\&P blender, delivering heated humidified blended gases through a Fisher-Paykel nasal mask. CPAP: CPAP therapy
FiO2 Change at 6 hours	0 Percentage of inspired oxygen Interval -7.0 to 0.0	0 Percentage of inspired oxygen Interval 0.0 to 0.0
FiO2 Change at 12 hours	0 Percentage of inspired oxygen Interval -10.0 to 0.0	0 Percentage of inspired oxygen Interval -17.0 to 0.0
FiO2 Change at 24 hours	-10 Percentage of inspired oxygen Interval -17.0 to 0.0	-15 Percentage of inspired oxygen Interval -20.0 to 0.0
FiO2 Change at 48 hours	-14.5 Percentage of inspired oxygen Interval -20.0 to -10.0	-12.5 Percentage of inspired oxygen Interval -20.0 to 0.0
FiO2 Change at 72 hours	-10 Percentage of inspired oxygen Interval -19.0 to -5.0	-7.5 Percentage of inspired oxygen Interval -14.5 to -2.5

SECONDARY outcome

Timeframe: 6, 12, 24, 48 and 72 hours after treatment commencement

Population: Number missing: 6 hrs: 1 Dolphin (failed), 0 FP 12 hrs: 1 Dolphin (failed), 1 FP (recovered) 24 hrs: 6 Dolphin (2 failed + 4 recovered), 4 FP (all recovered) 48 hrs: 16 Dolphin (3 failed + 13 recovered), 11 FP (1 failed + 10 recovered) 72 hrs: 21 Dolphin (3 failed + 18 recovered), 21 FP (1 failed + 20 recovered)

Oxygen saturation by pulse oximetry (SpO2), measured as a change from baseline Note. Outcome contaminated. An SpO2 target of 90-95% reflects currently recommended practice for neonates. The majority of readings were at SpO2 \> 95%, above SpO2 target (90-95%).

Outcome measures

Outcome measures
Measure	Dolphin CPAP n=26 Participants CPAP machine with oxygen intake and an on-board air compressor, and integrated blender and humidifier, delivering heated humidified blended gases through a Fisher-Paykel nasal mask. \[Also includes built-in Massimo pulse oximeter, though this is not used for this study, to prevent differential measurement error in SpO2 measurement\] CPAP: CPAP therapy	Fisher-Paykel CPAP n=25 Participants Fisher-Paykel (F\&P) CPAP machine with separate oxygen and medical air intakes, with third-party FP-compliant blender, and F\&P blender, delivering heated humidified blended gases through a Fisher-Paykel nasal mask. CPAP: CPAP therapy
SpO2 Change at 6 hours	2 Percentage capillary oxygen saturation Interval 0.0 to 3.0	1 Percentage capillary oxygen saturation Interval 0.0 to 3.0
SpO2 Change at 12 hours	2 Percentage capillary oxygen saturation Interval 0.0 to 3.0	1 Percentage capillary oxygen saturation Interval -0.5 to 3.5
SpO2 Change at 24 hours	1 Percentage capillary oxygen saturation Interval -1.0 to 2.5	0 Percentage capillary oxygen saturation Interval -2.0 to 1.0
SpO2 Change at 48 hours	1 Percentage capillary oxygen saturation Interval -4.0 to 1.0	-0.5 Percentage capillary oxygen saturation Interval -2.0 to 1.0
SpO2 Change at 72 hours	-1 Percentage capillary oxygen saturation Interval -5.0 to 4.0	-0.5 Percentage capillary oxygen saturation Interval -1.0 to 0.0

SECONDARY outcome

Timeframe: 6, 12, 24, 48 and 72 hours after treatment commencement

Population: Number missing (and thus imputed): 6 hrs: 1 Dolphin (failed), 0 FP 12 hrs: 1 Dolphin (failed), 1 FP (recovered) 24 hrs: 6 Dolphin (2 failed + 4 recovered), 4 FP (all recovered) 48 hrs: 16 Dolphin (3 failed + 13 recovered), 11 FP (1 failed + 10 recovered) 72 hrs: 21 Dolphin (3 failed + 18 recovered), 21 FP (1 failed + 20 recovered)

Respiratory rate (breaths/minute), measured as a change from baseline

Outcome measures

Outcome measures
Measure	Dolphin CPAP n=26 Participants CPAP machine with oxygen intake and an on-board air compressor, and integrated blender and humidifier, delivering heated humidified blended gases through a Fisher-Paykel nasal mask. \[Also includes built-in Massimo pulse oximeter, though this is not used for this study, to prevent differential measurement error in SpO2 measurement\] CPAP: CPAP therapy	Fisher-Paykel CPAP n=25 Participants Fisher-Paykel (F\&P) CPAP machine with separate oxygen and medical air intakes, with third-party FP-compliant blender, and F\&P blender, delivering heated humidified blended gases through a Fisher-Paykel nasal mask. CPAP: CPAP therapy
Respiratory Rate Change at 6 hours	-2 Breaths per minute Interval -2.0 to 3.0	0 Breaths per minute Interval -2.0 to 2.0
Respiratory Rate Change at 12 hours	0 Breaths per minute Interval -2.0 to 0.0	0 Breaths per minute Interval -2.0 to 2.0
Respiratory Rate Change at 24 hours	-2 Breaths per minute Interval -4.0 to 2.0	0 Breaths per minute Interval -2.0 to 2.0
Respiratory Rate Change at 48 hours	-1 Breaths per minute Interval -4.0 to 2.0	0 Breaths per minute Interval -2.0 to 2.0
Respiratory Rate Change at 72 hours	0 Breaths per minute Interval -2.0 to 4.0	0 Breaths per minute Interval -1.0 to 1.0

SECONDARY outcome

Timeframe: 6, 12, 24, 48 and 72 hours after treatment commencement (where available)

Population: Only 31/51 infants had a baseline blood gas taken, and only 7 of these had a second or subsequent test, with five of them at 6 hours, two each at 12 and 24 hours and one each at 48 and 72 hours. No statistical testing performed.

pH measured as a change from baseline (where measured)

Outcome measures

Outcome measures
Measure	Dolphin CPAP n=3 Participants CPAP machine with oxygen intake and an on-board air compressor, and integrated blender and humidifier, delivering heated humidified blended gases through a Fisher-Paykel nasal mask. \[Also includes built-in Massimo pulse oximeter, though this is not used for this study, to prevent differential measurement error in SpO2 measurement\] CPAP: CPAP therapy	Fisher-Paykel CPAP n=4 Participants Fisher-Paykel (F\&P) CPAP machine with separate oxygen and medical air intakes, with third-party FP-compliant blender, and F\&P blender, delivering heated humidified blended gases through a Fisher-Paykel nasal mask. CPAP: CPAP therapy
Arterial pH Change at 6 hours	0.135 pH Interval 0.08 to 0.19	0.05 pH Interval 0.0 to 0.53
Arterial pH Change at 12 hours	0.19 pH Interval 0.19 to 0.19	0.23 pH Interval 0.23 to 0.23
Arterial pH Change at 24 hours	0.015 pH Interval 0.0 to 0.03	—
Arterial pH Change at 48 hours	—	0.01 pH Interval 0.01 to 0.01
Arterial pH Change at 72 hours	—	-0.01 pH Interval -0.01 to -0.01

SECONDARY outcome

Timeframe: 6, 12, 24, 48 and 72 hours after treatment commencement (where available)

Population: Only 31/51 infants had a baseline blood gas taken, and only 7 of these had a second or subsequent test, with five of them at 6 hours, two each at 12 and 24 hours and one each at 48 and 72 hours. No statistical testing performed.

PaO2 measured as a change from baseline (where measured)

Outcome measures

Outcome measures
Measure	Dolphin CPAP n=3 Participants CPAP machine with oxygen intake and an on-board air compressor, and integrated blender and humidifier, delivering heated humidified blended gases through a Fisher-Paykel nasal mask. \[Also includes built-in Massimo pulse oximeter, though this is not used for this study, to prevent differential measurement error in SpO2 measurement\] CPAP: CPAP therapy	Fisher-Paykel CPAP n=4 Participants Fisher-Paykel (F\&P) CPAP machine with separate oxygen and medical air intakes, with third-party FP-compliant blender, and F\&P blender, delivering heated humidified blended gases through a Fisher-Paykel nasal mask. CPAP: CPAP therapy
Partial Pressure of Arterial Oxygen (PaO2) Change at 6 hours	-138 Torr Interval -179.0 to -97.0	-47 Torr Interval -67.0 to 0.0
Partial Pressure of Arterial Oxygen (PaO2) Change at 12 hours	-60.2 Torr Interval -60.2 to -60.2	12.1 Torr Interval 12.1 to 12.1
Partial Pressure of Arterial Oxygen (PaO2) Change at 24 hours	-42.5 Torr Interval -85.0 to 0.0	—
Partial Pressure of Arterial Oxygen (PaO2) Change at 48 hours	—	-9.3 Torr Interval -9.3 to -9.3
Partial Pressure of Arterial Oxygen (PaO2) Change at 72 hours	—	15.6 Torr Interval 15.6 to 15.6

SECONDARY outcome

Timeframe: 6, 12, 24, 48 and 72 hours after treatment commencement (where available)

Population: Only 31/51 infants had a baseline blood gas taken, and only 7 of these had a second or subsequent test, with five of them at 6 hours, two each at 12 and 24 hours and one each at 48 and 72 hours. No statistical testing performed.

PaCO2 measured as a change from baseline (where measured)

Outcome measures

Outcome measures
Measure	Dolphin CPAP n=3 Participants CPAP machine with oxygen intake and an on-board air compressor, and integrated blender and humidifier, delivering heated humidified blended gases through a Fisher-Paykel nasal mask. \[Also includes built-in Massimo pulse oximeter, though this is not used for this study, to prevent differential measurement error in SpO2 measurement\] CPAP: CPAP therapy	Fisher-Paykel CPAP n=4 Participants Fisher-Paykel (F\&P) CPAP machine with separate oxygen and medical air intakes, with third-party FP-compliant blender, and F\&P blender, delivering heated humidified blended gases through a Fisher-Paykel nasal mask. CPAP: CPAP therapy
Partial Pressure of Arterial Carbon Dioxide (PaCO2) Change at 6 hours	-17 Torr Interval -27.0 to -7.0	-9 Torr Interval -30.0 to 0.0
Partial Pressure of Arterial Carbon Dioxide (PaCO2) Change at 12 hours	-18.6 Torr Interval -18.6 to -18.6	-5.9 Torr Interval -5.9 to -5.9
Partial Pressure of Arterial Carbon Dioxide (PaCO2) Change at 24 hours	-12 Torr Interval -24.0 to 0.0	—
Partial Pressure of Arterial Carbon Dioxide (PaCO2) Change at 48 hours	—	-0.1 Torr Interval -0.1 to -0.1
Partial Pressure of Arterial Carbon Dioxide (PaCO2) Change at 72 hours	—	6.4 Torr Interval 6.4 to 6.4

SECONDARY outcome

Timeframe: From date and time of randomization to date and time of cessation of CPAP treatment, or until date and time of hospital discharge, if infant is on CPAP treatment until discharged (i.e., dies or is transferred), assessed to a maximum of 2 months of age.

Death or need for intubation and mechanical ventilation as demonstrated by an FiO2 requirement ≥ 60% for ≥ 1 hour to maintain SpO2 at 90-95% Note. An SpO2 target of 90-95% reflects currently recommended practice for neonates. FiO2 and SpO2 at time of intubation and ventilation not separately recorded, so we report this endpoint as recorded by clinicians, assuming that they have verified FiO2 \[≥ 60% for ≥ 1 hour\] and SpO2 \[targeting 90-95%\] requirements at the time of intubation and ventilation. If SpO2 was actually \>95% (not 90-95%) at the time of intubation and ventilation, then FiO2 would be higher than required to meet the target range, by an unknown amount (possibly not meeting the FiO2 threshold of ≥ 60% for ≥ 1 hour, required to justify intubation and ventilation). We note this potential source of contamination because the results of Outcome #2 show that the majority of SpO2 readings were \>95%.

Outcome measures

Outcome measures
Measure	Dolphin CPAP n=26 Participants CPAP machine with oxygen intake and an on-board air compressor, and integrated blender and humidifier, delivering heated humidified blended gases through a Fisher-Paykel nasal mask. \[Also includes built-in Massimo pulse oximeter, though this is not used for this study, to prevent differential measurement error in SpO2 measurement\] CPAP: CPAP therapy	Fisher-Paykel CPAP n=25 Participants Fisher-Paykel (F\&P) CPAP machine with separate oxygen and medical air intakes, with third-party FP-compliant blender, and F\&P blender, delivering heated humidified blended gases through a Fisher-Paykel nasal mask. CPAP: CPAP therapy
Number of Participants Who Died or Needed Intubation and/or Mechanical Ventilation, as a Measure of CPAP Failure, Measured to Date and Time of Cessation of CPAP Treatment	3 Participants	2 Participants

SECONDARY outcome

Timeframe: From date and time of randomization to date and time of cessation of CPAP treatment, or until date and time of hospital discharge, if infant is on CPAP treatment until discharged (i.e., dies or is transferred), assessed to a maximum of 2 months of age.

Surfactant provided when FiO2 \> 40% to maintain SpO2 at 90-95% for ≥ 30 minutes, with Respiratory Distress Syndrome confirmed by chest X-Ray Note that endpoint likely corrupted because SpO2 was not routinely targeting 90-95%, and large number of infants received surfactant before achieving \>40% or without having x-ray confirmation of RDS.

Outcome measures

Outcome measures
Measure	Dolphin CPAP n=26 Participants CPAP machine with oxygen intake and an on-board air compressor, and integrated blender and humidifier, delivering heated humidified blended gases through a Fisher-Paykel nasal mask. \[Also includes built-in Massimo pulse oximeter, though this is not used for this study, to prevent differential measurement error in SpO2 measurement\] CPAP: CPAP therapy	Fisher-Paykel CPAP n=25 Participants Fisher-Paykel (F\&P) CPAP machine with separate oxygen and medical air intakes, with third-party FP-compliant blender, and F\&P blender, delivering heated humidified blended gases through a Fisher-Paykel nasal mask. CPAP: CPAP therapy
Surfactant Provided When FiO2 > 40% to Maintain SpO2 at 90-95% for ≥ 30 Minutes, With Respiratory Distress Syndrome Confirmed by Chest X-Ray	3 Participants	1 Participants

SECONDARY outcome

Timeframe: From date and time of randomization to date and time of cessation of CPAP treatment, or until date and time of hospital discharge, if infant is on CPAP treatment until discharged (i.e., dies or is transferred), assessed to a maximum of 2 months of age.

Outcomes 6 or 7 Note that endpoint likely corrupted because SpO2 was not routinely targeting 90-95%, and large number of infants received surfactant before achieving \>40% or without having x-ray confirmation of RDS.

Outcome measures

Outcome measures
Measure	Dolphin CPAP n=26 Participants CPAP machine with oxygen intake and an on-board air compressor, and integrated blender and humidifier, delivering heated humidified blended gases through a Fisher-Paykel nasal mask. \[Also includes built-in Massimo pulse oximeter, though this is not used for this study, to prevent differential measurement error in SpO2 measurement\] CPAP: CPAP therapy	Fisher-Paykel CPAP n=25 Participants Fisher-Paykel (F\&P) CPAP machine with separate oxygen and medical air intakes, with third-party FP-compliant blender, and F\&P blender, delivering heated humidified blended gases through a Fisher-Paykel nasal mask. CPAP: CPAP therapy
CPAP Failure or Surfactant Provision	6 Participants	3 Participants

SECONDARY outcome

Timeframe: From date and time of randomization to date and time of cessation of CPAP treatment, or until date and time of hospital discharge, if infant is on CPAP treatment until discharged (i.e., dies or is transferred), assessed to a maximum of 2 months of age.

Population: Excludes 3 Dolphin and 2 FP randomised infants that failed treatment (escalated to mechanical ventilation)

Duration of CPAP treatment (hours) in infants that do not fail CPAP

Outcome measures

Outcome measures
Measure	Dolphin CPAP n=23 Participants CPAP machine with oxygen intake and an on-board air compressor, and integrated blender and humidifier, delivering heated humidified blended gases through a Fisher-Paykel nasal mask. \[Also includes built-in Massimo pulse oximeter, though this is not used for this study, to prevent differential measurement error in SpO2 measurement\] CPAP: CPAP therapy	Fisher-Paykel CPAP n=23 Participants Fisher-Paykel (F\&P) CPAP machine with separate oxygen and medical air intakes, with third-party FP-compliant blender, and F\&P blender, delivering heated humidified blended gases through a Fisher-Paykel nasal mask. CPAP: CPAP therapy
CPAP Duration	46.9 Hours Interval 42.1 to 70.0	56.5 Hours Interval 38.0 to 65.0

SECONDARY outcome

Timeframe: From date and time of birth to date and time of hospital discharge, assessed to a maximum of 2 months of age.

Population: The infant that died recovered after CPAP but was subsequently treated for apnea and a patent ductus arteriosus. Twelve days after CPAP cessation the infant commenced antibiotics for elevated CRP and was intubated and ventilated and died. The Data Safety Monitoring Committee determined that the death was unrelated to treatment group.

A Serious adverse Event (SAEs) is any untoward medial occurrence that: * Results in death; * Is life-threatening; \[NOTE: the term "life-threatening" in the definition of "serious" refers to an event in which the patient was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe.\] * Requires inpatient hospitalisation or prolongation of existing hospitalisation; * Results in persistent or significant disability/incapacity, or * Is a congenital anomaly/birth defect