Trial Outcomes & Findings for Nasal HFOV Versus Nasal SIPPV in Neonate Following Extubation: RCT Crossover Study (NCT NCT04323397)
NCT ID: NCT04323397
Last Updated: 2025-03-03
Results Overview
Data from the Crossover Phase of the study: After randomization only in neonate with arterial line, the initial non-invasive ventilation (NIV) was started then blood gas was obtained after 2 hours. The participant was switched to another NIV and blood gas was obtained after 2 hours.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
133 participants
Primary outcome timeframe
2 hours after each intervention
Results posted on
2025-03-03
Participant Flow
Overall, 203 neonates were assessed for eligibility
The 133 participants were included in the study.
Participant milestones
| Measure |
"nHFO First, Then nSIPPV, Then nHFO"
nHFO: flow 8-10 L/minute, frequency 10 Hz, MAP = "MAP (before extubation) + 2" or "8 (preterm), 10 (term)" cmH2O, dP = "2-3 times of MAP with visible chest oscillations" or 25-35 cmH2O, I:E = 1:1, FiO2 = "FiO2 (before extubation) + 0.1-0.2" keep targeted SpO2 90-94%
Non-invasive ventilation: Intervention nasal high frequency oscillatory ventilation (nHFOV) and nasal synchronized intermittent positive pressure ventilation (nSIPPV) were generated by neonatal ventilators (SLE6000 infant ventilators, United Kingdom) using bi-nasal prongs (RAM cannula, NEOTECH®, USA) or the nasal mask of the same type for both ventilation modes. The size of the prongs was determined by the infant's weight. The largest possible prongs were used, with a snug fit to avoid leakage. Pacifier for preterm and term neonate (Jollypop™, USA) was taken to avoid leakage from the mouth. The disposable ventilator circuit (Fisher \& Paykel RT268™, Evaqua Dual Limb Infant Breathing Circuit Kit with Evaqua 2 Technology and Pressure Line, Flow \> 4L/min, New Zealand) was used. The initial NIV setting was (7) described in arm description. (above)
|
"nSIPPV First, Then nHFOV, Then nSIPPV"
nSIPPV: flow 8-10 L/minute, rate 60/minute, PIP = "PIP (before extubation) + 2-5" or "20 (preterm), 25 (term)" cmH2O, PEEP = 5 cmH2O, IT = 0.5 s, FiO2 = "FiO2 (before extubation) + 0.1-0.2" keep targeted SpO2 90-94%. The highest trigger sensitivity avoiding auto triggering was selected.
Non-invasive ventilation: Intervention nasal high frequency oscillatory ventilation (nHFOV) and nasal synchronized intermittent positive pressure ventilation (nSIPPV) were generated by neonatal ventilators (SLE6000 infant ventilators, United Kingdom) using bi-nasal prongs (RAM cannula, NEOTECH®, USA) or the nasal mask of the same type for both ventilation modes. The size of the prongs was determined by the infant's weight. The largest possible prongs were used, with a snug fit to avoid leakage. Pacifier for preterm and term neonate (Jollypop™, USA) was taken to avoid leakage from the mouth. The disposable ventilator circuit (Fisher \& Paykel RT268™, Evaqua Dual Limb Infant Breathing Circuit Kit with Evaqua 2 Technology and Pressure Line, Flow \> 4L/min, New Zealand) was used. The initial NIV setting was (7) described in arm description. (above)
|
|---|---|---|
|
First Intervention
STARTED
|
51
|
51
|
|
First Intervention
COMPLETED
|
51
|
51
|
|
First Intervention
NOT COMPLETED
|
0
|
0
|
|
Second Intervention
STARTED
|
51
|
51
|
|
Second Intervention
COMPLETED
|
51
|
51
|
|
Second Intervention
NOT COMPLETED
|
0
|
0
|
|
Third Intervention
STARTED
|
67
|
66
|
|
Third Intervention
COMPLETED
|
67
|
66
|
|
Third Intervention
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
| Measure |
nHFOV, Then nSIPPV, Then nHFOV
n=67 Participants
nHFO: flow 8-10 L/minute, frequency 10 Hz, MAP = "MAP (before extubation) + 2" or "8 (preterm), 10 (term)" cmH2O, dP = "2-3 times of MAP with visible chest oscillations" or 25-35 cmH2O, I:E = 1:1, FiO2 = "FiO2 (before extubation) + 0.1-0.2" keep targeted SpO2 90-94%
Non-invasive ventilation: Intervention nasal high frequency oscillatory ventilation (nHFOV) and nasal synchronized intermittent positive pressure ventilation (nSIPPV) were generated by neonatal ventilators (SLE6000 infant ventilators, United Kingdom) using bi-nasal prongs (RAM cannula, NEOTECH®, USA) or the nasal mask of the same type for both ventilation modes. The size of the prongs was determined by the infant's weight. The largest possible prongs were used, with a snug fit to avoid leakage. Pacifier for preterm and term neonate (Jollypop™, USA) was taken to avoid leakage from the mouth. The disposable ventilator circuit (Fisher \& Paykel RT268™, Evaqua Dual Limb Infant Breathing Circuit Kit with Evaqua 2 Technology and Pressure Line, Flow \> 4L/min, New Zealand) was used. The initial NIV setting was (7) described in arm description. (above)
|
nSIPPV, Then nHFOV, Then nSIPPV
n=66 Participants
nSIPPV: flow 8-10 L/minute, rate 60/minute, PIP = "PIP (before extubation) + 2-5" or "20 (preterm), 25 (term)" cmH2O, PEEP = 5 cmH2O, IT = 0.5 s, FiO2 = "FiO2 (before extubation) + 0.1-0.2" keep targeted SpO2 90-94%. The highest trigger sensitivity avoiding auto triggering was selected.
Non-invasive ventilation: Intervention nasal high frequency oscillatory ventilation (nHFOV) and nasal synchronized intermittent positive pressure ventilation (nSIPPV) were generated by neonatal ventilators (SLE6000 infant ventilators, United Kingdom) using bi-nasal prongs (RAM cannula, NEOTECH®, USA) or the nasal mask of the same type for both ventilation modes. The size of the prongs was determined by the infant's weight. The largest possible prongs were used, with a snug fit to avoid leakage. Pacifier for preterm and term neonate (Jollypop™, USA) was taken to avoid leakage from the mouth. The disposable ventilator circuit (Fisher \& Paykel RT268™, Evaqua Dual Limb Infant Breathing Circuit Kit with Evaqua 2 Technology and Pressure Line, Flow \> 4L/min, New Zealand) was used. The initial NIV setting was (7) described in arm description. (above)
|
Total
n=133 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
33 weeks
n=67 Participants
|
33 weeks
n=66 Participants
|
33 weeks
n=133 Participants
|
|
Sex: Female, Male
Female
|
20 Participants
n=67 Participants
|
32 Participants
n=66 Participants
|
52 Participants
n=133 Participants
|
|
Sex: Female, Male
Male
|
47 Participants
n=67 Participants
|
34 Participants
n=66 Participants
|
81 Participants
n=133 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Duration of invasive ventilation
|
63.4 hours
n=67 Participants
|
42.9 hours
n=66 Participants
|
48.4 hours
n=133 Participants
|
PRIMARY outcome
Timeframe: 2 hours after each interventionData from the Crossover Phase of the study: After randomization only in neonate with arterial line, the initial non-invasive ventilation (NIV) was started then blood gas was obtained after 2 hours. The participant was switched to another NIV and blood gas was obtained after 2 hours.
Outcome measures
| Measure |
nHFO
n=102 Participants
nHFO: flow 8-10 L/minute, frequency 10 Hz, MAP = "MAP (before extubation) + 2" or "8 (preterm), 10 (term)" cmH2O, dP = "2-3 times of MAP with visible chest oscillations" or 25-35 cmH2O, I:E = 1:1, FiO2 = "FiO2 (before extubation) + 0.1-0.2" keep targeted SpO2 90-94%
Non-invasive ventilation: Intervention nasal high frequency oscillatory ventilation (nHFOV) and nasal synchronized intermittent positive pressure ventilation (nSIPPV) were generated by neonatal ventilators (SLE6000 infant ventilators, United Kingdom) using bi-nasal prongs (RAM cannula, NEOTECH®, USA) or the nasal mask of the same type for both ventilation modes. The size of the prongs was determined by the infant's weight. The largest possible prongs were used, with a snug fit to avoid leakage. Pacifier for preterm and term neonate (Jollypop™, USA) was taken to avoid leakage from the mouth. The disposable ventilator circuit (Fisher \& Paykel RT268™, Evaqua Dual Limb Infant Breathing Circuit Kit with Evaqua 2 Technology and Pressure Line, Flow \> 4L/min, New Zealand) was used. The initial NIV setting was (7) described in arm description. (above)
|
nSIPPV
n=102 Participants
nSIPPV: flow 8-10 L/minute, rate 60/minute, PIP = "PIP (before extubation) + 2-5" or "20 (preterm), 25 (term)" cmH2O, PEEP = 5 cmH2O, IT = 0.5 s, FiO2 = "FiO2 (before extubation) + 0.1-0.2" keep targeted SpO2 90-94%. The highest trigger sensitivity avoiding auto triggering was selected.
Non-invasive ventilation: Intervention nasal high frequency oscillatory ventilation (nHFOV) and nasal synchronized intermittent positive pressure ventilation (nSIPPV) were generated by neonatal ventilators (SLE6000 infant ventilators, United Kingdom) using bi-nasal prongs (RAM cannula, NEOTECH®, USA) or the nasal mask of the same type for both ventilation modes. The size of the prongs was determined by the infant's weight. The largest possible prongs were used, with a snug fit to avoid leakage. Pacifier for preterm and term neonate (Jollypop™, USA) was taken to avoid leakage from the mouth. The disposable ventilator circuit (Fisher \& Paykel RT268™, Evaqua Dual Limb Infant Breathing Circuit Kit with Evaqua 2 Technology and Pressure Line, Flow \> 4L/min, New Zealand) was used. The initial NIV setting was (7) described in arm description. (above)
|
|---|---|---|
|
Partial Pressure CO2 (pCO2) : Data From the Crossover Phase of the Study
|
38.7 mm Hg
Standard Deviation 8.8
|
36.8 mm Hg
Standard Deviation 10.2
|
SECONDARY outcome
Timeframe: up to 7 days after each interventionData from the Parallel Phase of the study: The participant with and without arterial line was randomized. If The participant with arterial line was randomized to cross-over trial (randomized to NIV, then switched to another NIV for 2 hours, then switched to the first NIV \[parallel trial\]). If The participant without arterial line was randomized to parallel trial. Extubation failure will be defined by reintubation after NIV mode.
Outcome measures
| Measure |
nHFO
n=67 Participants
nHFO: flow 8-10 L/minute, frequency 10 Hz, MAP = "MAP (before extubation) + 2" or "8 (preterm), 10 (term)" cmH2O, dP = "2-3 times of MAP with visible chest oscillations" or 25-35 cmH2O, I:E = 1:1, FiO2 = "FiO2 (before extubation) + 0.1-0.2" keep targeted SpO2 90-94%
Non-invasive ventilation: Intervention nasal high frequency oscillatory ventilation (nHFOV) and nasal synchronized intermittent positive pressure ventilation (nSIPPV) were generated by neonatal ventilators (SLE6000 infant ventilators, United Kingdom) using bi-nasal prongs (RAM cannula, NEOTECH®, USA) or the nasal mask of the same type for both ventilation modes. The size of the prongs was determined by the infant's weight. The largest possible prongs were used, with a snug fit to avoid leakage. Pacifier for preterm and term neonate (Jollypop™, USA) was taken to avoid leakage from the mouth. The disposable ventilator circuit (Fisher \& Paykel RT268™, Evaqua Dual Limb Infant Breathing Circuit Kit with Evaqua 2 Technology and Pressure Line, Flow \> 4L/min, New Zealand) was used. The initial NIV setting was (7) described in arm description. (above)
|
nSIPPV
n=66 Participants
nSIPPV: flow 8-10 L/minute, rate 60/minute, PIP = "PIP (before extubation) + 2-5" or "20 (preterm), 25 (term)" cmH2O, PEEP = 5 cmH2O, IT = 0.5 s, FiO2 = "FiO2 (before extubation) + 0.1-0.2" keep targeted SpO2 90-94%. The highest trigger sensitivity avoiding auto triggering was selected.
Non-invasive ventilation: Intervention nasal high frequency oscillatory ventilation (nHFOV) and nasal synchronized intermittent positive pressure ventilation (nSIPPV) were generated by neonatal ventilators (SLE6000 infant ventilators, United Kingdom) using bi-nasal prongs (RAM cannula, NEOTECH®, USA) or the nasal mask of the same type for both ventilation modes. The size of the prongs was determined by the infant's weight. The largest possible prongs were used, with a snug fit to avoid leakage. Pacifier for preterm and term neonate (Jollypop™, USA) was taken to avoid leakage from the mouth. The disposable ventilator circuit (Fisher \& Paykel RT268™, Evaqua Dual Limb Infant Breathing Circuit Kit with Evaqua 2 Technology and Pressure Line, Flow \> 4L/min, New Zealand) was used. The initial NIV setting was (7) described in arm description. (above)
|
|---|---|---|
|
Number of Participants With Extubation Failure: Data From the Parallel Phase of the Study.
|
5 Participants
|
4 Participants
|
Adverse Events
Parallel: Nasal High Frequency Oscillatory Ventilation
Serious events: 5 serious events
Other events: 0 other events
Deaths: 0 deaths
Parallel: Nasal Synchronized Intermittent Positive Pressure Ventilation
Serious events: 4 serious events
Other events: 0 other events
Deaths: 0 deaths
Crossover: Nasal High Frequency Oscillatory Ventilation
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Crossover: Nasal Synchronized Intermittent Positive Pressure Ventilation
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Parallel: Nasal High Frequency Oscillatory Ventilation
n=67 participants at risk
nHFO: flow 8-10 L/minute, frequency 10 Hz, MAP = "MAP (before extubation) + 2" or "8 (preterm), 10 (term)" cmH2O, dP = "2-3 times of MAP with visible chest oscillations" or 25-35 cmH2O, I:E = 1:1, FiO2 = "FiO2 (before extubation) + 0.1-0.2" keep targeted SpO2 90-94%
Non-invasive ventilation: Intervention nasal high frequency oscillatory ventilation (nHFOV) and nasal synchronized intermittent positive pressure ventilation (nSIPPV) were generated by neonatal ventilators (SLE6000 infant ventilators, United Kingdom) using bi-nasal prongs (RAM cannula, NEOTECH®, USA) or the nasal mask of the same type for both ventilation modes. The size of the prongs was determined by the infant's weight. The largest possible prongs were used, with a snug fit to avoid leakage. Pacifier for preterm and term neonate (Jollypop™, USA) was taken to avoid leakage from the mouth. The disposable ventilator circuit (Fisher \& Paykel RT268™, Evaqua Dual Limb Infant Breathing Circuit Kit with Evaqua 2 Technology and Pressure Line, Flow \> 4L/min, New Zealand) was used. The initial NIV setting was (7) described in arm description. (above)
|
Parallel: Nasal Synchronized Intermittent Positive Pressure Ventilation
n=66 participants at risk
nSIPPV: flow 8-10 L/minute, rate 60/minute, PIP = "PIP (before extubation) + 2-5" or "20 (preterm), 25 (term)" cmH2O, PEEP = 5 cmH2O, IT = 0.5 s, FiO2 = "FiO2 (before extubation) + 0.1-0.2" keep targeted SpO2 90-94%. The highest trigger sensitivity avoiding auto triggering was selected.
Non-invasive ventilation: Intervention nasal high frequency oscillatory ventilation (nHFOV) and nasal synchronized intermittent positive pressure ventilation (nSIPPV) were generated by neonatal ventilators (SLE6000 infant ventilators, United Kingdom) using bi-nasal prongs (RAM cannula, NEOTECH®, USA) or the nasal mask of the same type for both ventilation modes. The size of the prongs was determined by the infant's weight. The largest possible prongs were used, with a snug fit to avoid leakage. Pacifier for preterm and term neonate (Jollypop™, USA) was taken to avoid leakage from the mouth. The disposable ventilator circuit (Fisher \& Paykel RT268™, Evaqua Dual Limb Infant Breathing Circuit Kit with Evaqua 2 Technology and Pressure Line, Flow \> 4L/min, New Zealand) was used. The initial NIV setting was (7) described in arm description. (above)
|
Crossover: Nasal High Frequency Oscillatory Ventilation
n=102 participants at risk
nHFO: flow 8-10 L/minute, frequency 10 Hz, MAP = "MAP (before extubation) + 2" or "8 (preterm), 10 (term)" cmH2O, dP = "2-3 times of MAP with visible chest oscillations" or 25-35 cmH2O, I:E = 1:1, FiO2 = "FiO2 (before extubation) + 0.1-0.2" keep targeted SpO2 90-94%
|
Crossover: Nasal Synchronized Intermittent Positive Pressure Ventilation
n=102 participants at risk
nSIPPV: flow 8-10 L/minute, rate 60/minute, PIP = "PIP (before extubation) + 2-5" or "20 (preterm), 25 (term)" cmH2O, PEEP = 5 cmH2O, IT = 0.5 s, FiO2 = "FiO2 (before extubation) + 0.1-0.2" keep targeted SpO2 90-94%. The highest trigger sensitivity avoiding auto triggering was selected.
|
|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Adverse Event after started intervention
|
7.5%
5/67 • Number of events 5 • Adverse event: "Crossover Phase: up to 4 hours, Parallel Phase: up to 7 days after intervention"
"Crossover Phase: up to 6 hours (participants = 51 neonate, 102 periods each arm for crossover), Parallel Phase: up to 7 days after intervention (participants = 67+66 = 133 participants)"
|
6.1%
4/66 • Number of events 4 • Adverse event: "Crossover Phase: up to 4 hours, Parallel Phase: up to 7 days after intervention"
"Crossover Phase: up to 6 hours (participants = 51 neonate, 102 periods each arm for crossover), Parallel Phase: up to 7 days after intervention (participants = 67+66 = 133 participants)"
|
0.00%
0/102 • Adverse event: "Crossover Phase: up to 4 hours, Parallel Phase: up to 7 days after intervention"
"Crossover Phase: up to 6 hours (participants = 51 neonate, 102 periods each arm for crossover), Parallel Phase: up to 7 days after intervention (participants = 67+66 = 133 participants)"
|
0.98%
1/102 • Number of events 1 • Adverse event: "Crossover Phase: up to 4 hours, Parallel Phase: up to 7 days after intervention"
"Crossover Phase: up to 6 hours (participants = 51 neonate, 102 periods each arm for crossover), Parallel Phase: up to 7 days after intervention (participants = 67+66 = 133 participants)"
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place