Respiratory Distress Syndrome In Premature InfantsNCT01962818
High Frequency Oscillatory Ventilation Combined With Intermittent Sigh Breaths: Effects on Lung Volume Monitored by Electric Tomography Impedance.
A study testing HFOV combined with sigh breaths in people with Respiratory Distress Syndrome In Premature Infants and Bronchopulmonary Dysplasia, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Australia.
Trial summary
Background Ventilator induced lung injury (VILI) remains a problem in neonatology. High frequency oscillatory ventilation (HFOV) provides effective gas exchange with minimal pressure fluctuation around a continuous distending pressure and therefore small tidal volume. Read more about this study
- Who is it for?
- Ages 24 to 44 weeks
- Conditions the study is for
- Respiratory Distress Syndrome In Premature Infants, Bronchopulmonary Dysplasia, Ventilator-Induced Lung Injury
- What is being tested?
- HFOV combined with sigh breaths
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteAustralia
- Study dates
- Jan 2014to 1 Jan 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 24 to 44 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Infants at 24-36 weeks corrected gestational age
- Already ventilated with high frequency ventilation
- Requiring FiO2=21%-70% to maintain adequate oxygen saturation.
- Clinical stable
- o i.e. ventilated on current settings for more than just a few hours with stable but not necessarily normalized blood gases or transcutaneous values and oxygen requirement.
- Parent(s) or guardian able and willing to provide informed consent
Show all 10Show fewer
- Exclusion Criteria: • Major congenital cardiovascular or respiratory abnormalities (excluding Patent ductus arteriosus).
- Poor skin integrity precluding use of adhesive ECG electrodes used for EIT monitoring.
- The physician responsible for the baby considers one of the ventilation modes unsuitable for the infant or the patient unsuitable for EIT monitoring.
- Lack of parental signed written informed consent or if both parents are under 18 years of age (due to complexities of obtaining consent).
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
Australia1 site
Department of Neonatology, Mater Mothers Hospital
Brisbane, Queensland, 4101
About this study
Official title: High Frequency Oscillatory Ventilation Combined With Intermittent Sigh Breaths in Neonates Compared With Standard High Frequency Oscillatory Ventilation - Effects on Lung Volume Monitored by Electric Tomography Impedance
Background Ventilator induced lung injury (VILI) remains a problem in neonatology. High frequency oscillatory ventilation (HFOV) provides effective gas exchange with minimal pressure fluctuation around a continuous distending pressure and therefore small tidal volume. Animal studies showed that recruitment and maintenance of functional residual capacity (FRC) during HFOV ("open lung concept") could reduce lung injury.
"Open lung HFOV" is achieved by delivering a moderate high mean airway pressure (MAP) using oxygenation as a guide of lung recruitment. Some neonatologists suggest combining HFOV with recurrent sigh-breaths (HFOV-sigh) delivered as modified conventional ventilator-breaths at a rate of 3/min. The clinical observation is that HFOV-sigh leads to more stable oxygenation, quicker weaning and shorter ventilation. This may be related to improved lung recruitment.
Read more
Electric Impedance Tomography (EIT) enables measurement and mapping of regional ventilation distribution and end-expiratory lung volume (EELV). EIT generates cross-sectional images of the subject based on measurement of surface electrical potentials resulting from an excitation with small electrical currents and has been shown to be a valid and safe tool in neonates.
Purpose, aims:
- To compare HFOV-sigh with HFOV-only and determine if there is a difference in global and regional EELV (primary endpoints) and spatial distribution of ventilation measured by EIT
- To provide information on feasibility and treatment effect of HFOV-sigh to assist planning larger studies. We hypothesize that EELV during HFOV-sigh is higher, and that regional ventilation distribution is more homogenous.
Methods:
Infants at 24-36 weeks corrected gestational age already on HFOV are eligible. Patients will be randomly assigned to HFOV-sigh (3 breaths/min) followed by HFOV-only or vice versa for 4 alternating 1-hours periods (2-treatment, double crossover design, each patient being its own control). During HFOV-sigh set-pressure will be reduced to keep MAP constant, otherwise HFOV will remain at pretrial settings.
16 ECG-electrodes for EIT recording will be placed around the chest at study start. Each recording will last 180s, and will be done at baseline and at 30 and 50 minutes after each change in ventilator modus.
Feasibility No information of EIT-measured EELV in babies on HFOV-sigh exists. This study is a pilot-trial.
In a similar study-protocol of lung recruitment during HFOV-sigh using "a/A-ratio" as outcome, 16 patients was estimated to be sufficient to show an improvement by 25%. This assumption was based on clinical experience in a unit using HFOV-sigh routinely. As the present study examines the same intervention we assume that N=16 patients will be a sufficient sample size. We estimate to include this number in 6 months.
Read the detailed description
Ventilator induced lung injury (VILI) is an important etiological factor in the pathogenesis of bronchopulmonary dysplasia (BPD), defined as need for respiratory support or supplemental oxygen at 36 weeks post-conceptual age. Despite advances in antenatal and neonatal care, 50-80% of very-low-birth-weight infants will be ventilated during their neonatal admission. Accordingly, further development of neonatal ventilation strategies with specific emphasis on lung-protective ventilation remains an important research field. Volutrauma and atelectotrauma caused by excessive tidal volume and insufficient lung recruitment respectively rather than barotrauma are today considered as the most important factors for VILI. High frequency oscillatory ventilation (HFOV) provides effective gas exchange with minimal pressure fluctuation around a continuous distending pressure and therefore small tidal volume and is in theory more lung protective. However results from randomized controlled trials comparing HFOV with conventional ventilation have been conflicting and meta-analyses have not shown clear evidence that HFOV is safer or more effective than conventional ventilation neither when used as initial strategy nor as rescue strategy in preterm babies. Accordingly HFOV still has no absolute indication and is mostly used as a rescue treatment. Early animal studies showed that recruitment and maintenance of functional residual capacity (FRC) during HFOV ("open lung concept") could reduce lung injury. Because of fear of barotrauma, lung recruitment was initially achieved by superimposing conventional ventilation (CV) breaths on top of HFOV with much lower mean airway pressure (MAP) than what is used today. Today most neonatologists provide "open lung HFOV" by delivering a higher MAP using oxygenation as an indirect guide of lung recruitment. In some units a clinical praxis has evolved combining HFOV (using "modern" high MAP) with recurrent sigh-breaths (HFOV-sigh) delivered as modified conventional inflations at a rate of 3/min. The clinical observation is, that when compared to standard HFOV, HFOV-sigh leads to more stable oxygenation, quicker weaning in FiO2 and MAP, and shorter ventilation. This approach seems to be encouraged by a number of neonatologist.
Electric Impedance Tomography (EIT) enables measurement and mapping of regional ventilation distribution, end-expiratory lung volume (EELV) and other respiratory physiological parameters. EIT generates cross-sectional images of the studied subject based on the measurement of surface electrical potentials resulting from an excitation with known small electrical currents (5 mAmp and 50 kHz). Both the voltage measurements and current injections take place between pairs of conventional self-adhesive surface electrodes of a 16-electrode array attached on the chest circumference. Electrical impedance tomography scans are generated from the collected potential differences and the known excitation currents using weighted back-projection in a 32x32 pixel matrix. Each pixel of the scan shows the instantaneous local impedance. EIT has been shown to be a valid and safe tool in neonates to monitor changes in global and regional lung ventilation and EELV.
Combining HFOV with conventional breaths has only been reported in a limited number of studies and only with focus on HFOV combined with conventional breaths at normal rate showing a possible benefit. Similar results have been reported when comparing High frequency Jet Ventilation (HFVJ) combined with conventional breaths at normal rate with HFVJ alone. To our knowledge only one human trial comparing standard HFOV with HFOV combined with recruitment breaths at low rate has been registered but never published (Texas Infant Star Trial).
The clinical observation is that oxygenation during HFOV-sigh seems to be improved which is considered to be an indirect sign of improved lung volume. However no clinical studies estimating lung volume during HFOV-sigh exist to confirm or dispute this, which is the main reason we propose this study.
Ideally, during HFOV the MAP should be set at a level at which lung volume is optimal. However in some situations the cardiovascular status of the patient does not allow the MAP to be increased to this level, in which case combining HFOV with sigh-breaths at a lower MAP could be an alternative way of optimizing lung volume.
The purpose of this study is to investigate the effect of HFOV-sigh compared with HFOV-only on EIT derived measurements of EELV and regional ventilation distribution and other respiratory physiological parameters such as heart rate and respiratory rate.
Research question:
In ventilated newborn infants, does combining high frequency oscillatory ventilation (HFOV) with intermittent sigh breaths result in increased end-expiratory lung volume (EELV) and more homogenous distribution of ventilation when compared to standard HFOV without sigh-breaths. Lung volume and distribution of ventilation will be monitored by electric impedance tomography (EIT).
Hypothesis and Aims of project:
Primary hypothesis of the study is that end-expiratory lung volume (EELV) during HFOV combined with sigh-breaths (HFOV-sigh) is relatively higher than EELV during HFOV without HFOV (HFOV-only), and that regional distribution of ventilation will be more homogenous indicating a more homogenous lung-recruitment. The following specific aims of this study will address these hypotheses:
- To determine if there is a significant difference in global and regional EELV measured by EIT between HFOV-sigh and HFOV-only
- To determine if there is a significant difference in spatial distribution of ventilation and timing of ventilation between HFOV-sigh and HFOV-only using specific EIT derived calculation
- To determine if there is a significant difference in other respiratory variables, such as heart rate (HR), oxygen saturation (SpO2) and spontaneous breathing rate between HFOV-sigh and HFOV-only
- To provide information on feasibility and data on treatment effect of HFOV-sigh to assist in planning a larger study.
- Conditions
- Respiratory Distress Syndrome In Premature Infants, Bronchopulmonary Dysplasia, Ventilator-Induced Lung Injury, Functional Residual Capacity
- Being tested
- HFOV combined with sigh breaths
- Keywords
- Respiratory Distress Syndrome In Premature Infants, Bronchopulmonary Dysplasia, Ventilator-Induced Lung Injury, Functional Residual Capacity, Electric impedance tomography
- Medical subject headings
- Respiratory Distress Syndrome In Premature Infants, Bronchopulmonary Dysplasia, Ventilator-Induced Lung Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HFOV combined with sigh breathsOther
It is planned only to investigate infants already ventilated on the HFOV-modus on high frequency oscillators, where the HFOV modus can be superimposed on conventional modes of ventilation. This gives the opportunity to combine HFOV with intermittent sigh breaths with a pre-set frequency and pre-set peak inspiratory pressure (PIP) and thus comparing HFOV combined with sigh breaths (HFOV-sigh) with conventional HFOV (HFOV-only).
All included participants will be exposed to the two different ventilator strategies tested in this trial, albeit in alternating and different order.
Each patient will serve, as it's own control. The trial will involve four alternating 1-hours periods allowing a sufficient "wash-out" period, as it has been shown that alveolar recruitment and derecruitment may take up to 25 min after changes to ventilator pressures At study start the patients will randomly be assigned to either starting with HFOV-only or HFOV-sigh
| Study group | Role | What they receive |
|---|---|---|
| HFOV-sigh at start | Experimental | Each patient will be exposed to either HFOV alone (HFOV-only) or HFOV combined with sigh breaths (HFOV-sigh), but in different order.
MAP=mean airway pressure.
DURING HFOV-SIGH:
Frequency 3 breaths/min Ti = 1s Peak inspiratory pressure (PIP) = 30 cm H2O
For patients already on HFOV-sigh at study start:
• MAP-set will be left unchanged at pre-trial settings.
For patients on HFOV-only at study start:
• During periods with superimposed sigh breaths, MAP-set will be reduced in accordance with a calculation of MAP aiming to keep average mean airway-pressure (MAP) unchanged. (MAP=(PIP*Tinsp+PEEP*Texp)/(Tinsp+Texp)
DURING HFOV-ONLY
For patients on HFOV-sigh at study start:
• During HFOV-only, the MAP-set will be increased in accordance with a calculation of MAP, aiming to keep average mean airway-pressure (MAP) unchanged.
For patients on HFOV-only at study start:
• MAP-set will be left unchanged at pre-trial settings. Receives: Other: HFOV combined with sigh breaths |
| HFOV-only at start | Experimental | Each patient will be exposed to either HFOV alone (HFOV-only) or HFOV combined with sigh breaths (HFOV-sigh), but in different order.
MAP=mean airway pressure.
DURING HFOV-SIGH:
Frequency 3 breaths/min Ti = 1s Peak inspiratory pressure (PIP) = 30 cm H2O
For patients already on HFOV-sigh at study start:
• MAP-set will be left unchanged at pre-trial settings.
For patients on HFOV-only at study start:
• During periods with superimposed sigh breaths, MAP-set will be reduced in accordance with a calculation of MAP aiming to keep average mean airway-pressure (MAP) unchanged. (MAP=(PIP*Tinsp+PEEP*Texp)/(Tinsp+Texp)
DURING HFOV-ONLY
For patients on HFOV-sigh at study start:
• During HFOV-only, the MAP-set will be increased in accordance with a calculation of MAP, aiming to keep average mean airway-pressure (MAP) unchanged.
For patients on HFOV-only at study start:
• MAP-set will be left unchanged at pre-trial settings. Receives: Other: HFOV combined with sigh breaths |
What is being measured
The primary outcome is the main question the study is designed to answer.
Global changes in end expiratory lung volume (EELV)
Relative difference in EELV expressed as difference in end-expiratory lung impedance during HFOV-only and HFOV-sigh
Measured: all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day.
Regional ventilation distribution
Relative difference in regional EELV during HFOV-sigh vs HFOV-only expressed as change in regional end-expiratory lung impedance in predefined regions of interests (ROI), such as e.g. ventral, mid-ventral, mid-dorsal and dorsal lung areas.
Measured: all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day.
Secondary outcomes (6)
Global changes in oscillatory volume (Vosv):
Relative difference in oscillatory volume expressed as change in impedance amplitude during HFOV-only and HFOV-sigh, if measurable
Measured: all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day.
Regional difference in oscillatory volume
Relative difference in regional oscillatory volume expressed as change in impedance amplitude during HFOV-only and HFOV-sigh in predefined regions of interests (ROI), such as e.g. ventral, mid-ventral, mid-dorsal and dorsal
Measured: all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day.
Regional distribution of sigh-breaths volume
Regional distribution of sigh-breaths during HFOV-sigh based on impedance amplitude of sigh-breaths in predefined ROIs, such as e.g. ventral, mid-ventral, mid-dorsal and dorsal
Measured: all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day.
Global inhomogeneity index
Calculated for oscillatory volume and tidal volume during sigh breaths respectively
Measured: all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day.
Phase angle analyses
- Description of regional filling characteristic by phase angle analysis, measuring synchronicity of emptying and filling of different lung regions during sigh-breaths.
- Aim to analyse if a possible increase in EELV during HFOV-sigh is distributed to different ROIs with different timing.
Measured: all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day.
vital parameters during HFOV-sigh vs HFOV-only
relative changes in fraction of inspired oxygen (FiO2), oxygensaturation and heart rate
Measured: all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2013 (estimated)
- Study startJan 2014
- Primary completionJul 2018
- Study completion1 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Respiratory Distress Syndrome In Premature InfantsStudies of the same condition, open and under way.
- More trials run by Copenhagen University Hospital, RigshospitaletThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital, Rigshospitalet
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Christian Heiring, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Christian Heiring, neonatologist, Principal investigator, Department of Neonatology, Rigshospitalet, CopenhagenLuke Jardine, neonatologist, Principal investigator, Department of Neonatology, Mater Mothers Hospital, Brisbane, Australia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01962818
- Sponsor's protocol ID
- 1936M
- Status last verified
- Mar 2023
- First submitted
- 9 Oct 2013
- Last updated
- 22 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- High Frequency Oscillatory Ventilation Combined With Intermittent Sigh Breaths in Neonates Compared With Standard High Frequency Oscillatory Ventilation - Effects on Lung Volume Monitored by Electric Tomography Impedance
- ClinicalTrials.gov ID
- NCT01962818
- Acronym / sponsor ID
- 1936M
- Conditions
- Respiratory Distress Syndrome In Premature Infants, Bronchopulmonary Dysplasia, Ventilator-Induced Lung Injury, Functional Residual Capacity
- Keywords
- Respiratory Distress Syndrome In Premature Infants, Bronchopulmonary Dysplasia, Ventilator-Induced Lung Injury, Functional Residual Capacity, Electric impedance tomography
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Copenhagen University Hospital, RigshospitaletUniversity, hospital or other
- Study start
- Jan 2014 (actual)
- Primary completion
- Jul 2018 (actual)
- Study completion
- 1 Jan 2023 (actual)
- First posted
- 14 Oct 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background Ventilator induced lung injury (VILI) remains a problem in neonatology. High frequency oscillatory ventilation (HFOV) provides effective gas exchange with minimal pressure fluctuation around a continuous distending pressure and therefore small tidal volume. Animal studies showed that recruitment and maintenance of functional residual capacity (FRC) during HFOV ("open lung concept") could reduce lung injury.
"Open lung HFOV" is achieved by delivering a moderate high mean airway pressure (MAP) using oxygenation as a guide of lung recruitment. Some neonatologists suggest combining HFOV with recurrent sigh-breaths (HFOV-sigh) delivered as modified conventional ventilator-breaths at a rate of 3/min. The clinical observation is that HFOV-sigh leads to more stable oxygenation, quicker weaning and shorter ventilation. This may be related to improved lung recruitment.
Electric Impedance Tomography (EIT) enables measurement and mapping of regional ventilation distribution and end-expiratory lung volume (EELV). EIT generates cross-sectional images of the subject based on measurement of surface electrical potentials resulting from an excitation with small electrical currents and has been shown to be a valid and safe tool in neonates.
Purpose, aims:
- To compare HFOV-sigh with HFOV-only and determine if there is a difference in global and regional EELV (primary endpoints) and spatial distribution of ventilation measured by EIT
- To provide information on feasibility and treatment effect of HFOV-sigh to assist planning larger studies. We hypothesize that EELV during HFOV-sigh is higher, and that regional ventilation distribution is more homogenous.
Methods:
Infants at 24-36 weeks corrected gestational age already on HFOV are eligible. Patients will be randomly assigned to HFOV-sigh (3 breaths/min) followed by HFOV-only or vice versa for 4 alternating 1-hours periods (2-treatment, double crossover design, each patient being its own control). During HFOV-sigh set-pressure will be reduced to keep MAP constant, otherwise HFOV will remain at pretrial settings.
16 ECG-electrodes for EIT recording will be placed around the chest at study start. Each recording will last 180s, and will be done at baseline and at 30 and 50 minutes after each change in ventilator modus.
Feasibility No information of EIT-measured EELV in babies on HFOV-sigh exists. This study is a pilot-trial.
In a similar study-protocol of lung recruitment during HFOV-sigh using "a/A-ratio" as outcome, 16 patients was estimated to be sufficient to show an improvement by 25%. This assumption was based on clinical experience in a unit using HFOV-sigh routinely. As the present study examines the same intervention we assume that N=16 patients will be a sufficient sample size. We estimate to include this number in 6 months.
Detailed description
Ventilator induced lung injury (VILI) is an important etiological factor in the pathogenesis of bronchopulmonary dysplasia (BPD), defined as need for respiratory support or supplemental oxygen at 36 weeks post-conceptual age. Despite advances in antenatal and neonatal care, 50-80% of very-low-birth-weight infants will be ventilated during their neonatal admission. Accordingly, further development of neonatal ventilation strategies with specific emphasis on lung-protective ventilation remains an important research field. Volutrauma and atelectotrauma caused by excessive tidal volume and insufficient lung recruitment respectively rather than barotrauma are today considered as the most important factors for VILI. High frequency oscillatory ventilation (HFOV) provides effective gas exchange with minimal pressure fluctuation around a continuous distending pressure and therefore small tidal volume and is in theory more lung protective. However results from randomized controlled trials comparing HFOV with conventional ventilation have been conflicting and meta-analyses have not shown clear evidence that HFOV is safer or more effective than conventional ventilation neither when used as initial strategy nor as rescue strategy in preterm babies. Accordingly HFOV still has no absolute indication and is mostly used as a rescue treatment. Early animal studies showed that recruitment and maintenance of functional residual capacity (FRC) during HFOV ("open lung concept") could reduce lung injury. Because of fear of barotrauma, lung recruitment was initially achieved by superimposing conventional ventilation (CV) breaths on top of HFOV with much lower mean airway pressure (MAP) than what is used today. Today most neonatologists provide "open lung HFOV" by delivering a higher MAP using oxygenation as an indirect guide of lung recruitment. In some units a clinical praxis has evolved combining HFOV (using "modern" high MAP) with recurrent sigh-breaths (HFOV-sigh) delivered as modified conventional inflations at a rate of 3/min. The clinical observation is, that when compared to standard HFOV, HFOV-sigh leads to more stable oxygenation, quicker weaning in FiO2 and MAP, and shorter ventilation. This approach seems to be encouraged by a number of neonatologist.
Electric Impedance Tomography (EIT) enables measurement and mapping of regional ventilation distribution, end-expiratory lung volume (EELV) and other respiratory physiological parameters. EIT generates cross-sectional images of the studied subject based on the measurement of surface electrical potentials resulting from an excitation with known small electrical currents (5 mAmp and 50 kHz). Both the voltage measurements and current injections take place between pairs of conventional self-adhesive surface electrodes of a 16-electrode array attached on the chest circumference. Electrical impedance tomography scans are generated from the collected potential differences and the known excitation currents using weighted back-projection in a 32x32 pixel matrix. Each pixel of the scan shows the instantaneous local impedance. EIT has been shown to be a valid and safe tool in neonates to monitor changes in global and regional lung ventilation and EELV.
Combining HFOV with conventional breaths has only been reported in a limited number of studies and only with focus on HFOV combined with conventional breaths at normal rate showing a possible benefit. Similar results have been reported when comparing High frequency Jet Ventilation (HFVJ) combined with conventional breaths at normal rate with HFVJ alone. To our knowledge only one human trial comparing standard HFOV with HFOV combined with recruitment breaths at low rate has been registered but never published (Texas Infant Star Trial).
The clinical observation is that oxygenation during HFOV-sigh seems to be improved which is considered to be an indirect sign of improved lung volume. However no clinical studies estimating lung volume during HFOV-sigh exist to confirm or dispute this, which is the main reason we propose this study.
Ideally, during HFOV the MAP should be set at a level at which lung volume is optimal. However in some situations the cardiovascular status of the patient does not allow the MAP to be increased to this level, in which case combining HFOV with sigh-breaths at a lower MAP could be an alternative way of optimizing lung volume.
The purpose of this study is to investigate the effect of HFOV-sigh compared with HFOV-only on EIT derived measurements of EELV and regional ventilation distribution and other respiratory physiological parameters such as heart rate and respiratory rate.
Research question:
In ventilated newborn infants, does combining high frequency oscillatory ventilation (HFOV) with intermittent sigh breaths result in increased end-expiratory lung volume (EELV) and more homogenous distribution of ventilation when compared to standard HFOV without sigh-breaths. Lung volume and distribution of ventilation will be monitored by electric impedance tomography (EIT).
Hypothesis and Aims of project:
Primary hypothesis of the study is that end-expiratory lung volume (EELV) during HFOV combined with sigh-breaths (HFOV-sigh) is relatively higher than EELV during HFOV without HFOV (HFOV-only), and that regional distribution of ventilation will be more homogenous indicating a more homogenous lung-recruitment. The following specific aims of this study will address these hypotheses:
- To determine if there is a significant difference in global and regional EELV measured by EIT between HFOV-sigh and HFOV-only
- To determine if there is a significant difference in spatial distribution of ventilation and timing of ventilation between HFOV-sigh and HFOV-only using specific EIT derived calculation
- To determine if there is a significant difference in other respiratory variables, such as heart rate (HR), oxygen saturation (SpO2) and spontaneous breathing rate between HFOV-sigh and HFOV-only
- To provide information on feasibility and data on treatment effect of HFOV-sigh to assist in planning a larger study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HFOV-sigh at start | Experimental | Other: HFOV combined with sigh breathsEach patient will be exposed to either HFOV alone (HFOV-only) or HFOV combined with sigh breaths (HFOV-sigh), but in different order. MAP=mean airway pressure. DURING HFOV-SIGH: Frequency 3 breaths/min Ti = 1s Peak inspiratory pressure (PIP) = 30 cm H2O For patients already on HFOV-sigh at study start: • MAP-set will be left unchanged at pre-trial settings. For patients on HFOV-only at study start: • During periods with superimposed sigh breaths, MAP-set will be reduced in accordance with a calculation of MAP aiming to keep average mean airway-pressure (MAP) unchanged. (MAP=(PIP*Tinsp+PEEP*Texp)/(Tinsp+Texp) DURING HFOV-ONLY For patients on HFOV-sigh at study start: • During HFOV-only, the MAP-set will be increased in accordance with a calculation of MAP, aiming to keep average mean airway-pressure (MAP) unchanged. For patients on HFOV-only at study start: • MAP-set will be left unchanged at pre-trial settings. |
| HFOV-only at start | Experimental | Other: HFOV combined with sigh breathsEach patient will be exposed to either HFOV alone (HFOV-only) or HFOV combined with sigh breaths (HFOV-sigh), but in different order. MAP=mean airway pressure. DURING HFOV-SIGH: Frequency 3 breaths/min Ti = 1s Peak inspiratory pressure (PIP) = 30 cm H2O For patients already on HFOV-sigh at study start: • MAP-set will be left unchanged at pre-trial settings. For patients on HFOV-only at study start: • During periods with superimposed sigh breaths, MAP-set will be reduced in accordance with a calculation of MAP aiming to keep average mean airway-pressure (MAP) unchanged. (MAP=(PIP*Tinsp+PEEP*Texp)/(Tinsp+Texp) DURING HFOV-ONLY For patients on HFOV-sigh at study start: • During HFOV-only, the MAP-set will be increased in accordance with a calculation of MAP, aiming to keep average mean airway-pressure (MAP) unchanged. For patients on HFOV-only at study start: • MAP-set will be left unchanged at pre-trial settings. |
Who may qualify
- Ages
- 24 to 44 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (10 listed)
- Infants at 24-36 weeks corrected gestational age
- Already ventilated with high frequency ventilation
- Requiring FiO2=21%-70% to maintain adequate oxygen saturation.
- Clinical stable
- o i.e. ventilated on current settings for more than just a few hours with stable but not necessarily normalized blood gases or transcutaneous values and oxygen requirement.
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HFOV combined with sigh breathsIt is planned only to investigate infants already ventilated on the HFOV-modus on high frequency oscillators, where the HFOV modus can be superimposed on conventional modes of ventilation. This gives the opportunity to combine HFOV with intermittent sigh breaths with a pre-set frequency and pre-set peak inspiratory pressure (PIP) and thus comparing HFOV combined with sigh breaths (HFOV-sigh) with conventional HFOV (HFOV-only). All included participants will be exposed to the two different ventilator strategies tested in this trial, albeit in alternating and different order. Each patient will serve, as it's own control. The trial will involve four alternating 1-hours periods allowing a sufficient "wash-out" period, as it has been shown that alveolar recruitment and derecruitment may take up to 25 min after changes to ventilator pressures At study start the patients will randomly be assigned to either starting with HFOV-only or HFOV-sigh | Other | HFOV-only at start, HFOV-sigh at start |
Primary outcome
Global changes in end expiratory lung volume (EELV)
Time frame: all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day.
Relative difference in EELV expressed as difference in end-expiratory lung impedance during HFOV-only and HFOV-sigh
Regional ventilation distribution
Time frame: all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day.
Relative difference in regional EELV during HFOV-sigh vs HFOV-only expressed as change in regional end-expiratory lung impedance in predefined regions of interests (ROI), such as e.g. ventral, mid-ventral, mid-dorsal and dorsal lung areas.
6 secondary outcomes
Global changes in oscillatory volume (Vosv):
Time frame: all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day.
Regional difference in oscillatory volume
Time frame: all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day.
Regional distribution of sigh-breaths volume
Time frame: all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day.
Global inhomogeneity index
Time frame: all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day.
Phase angle analyses
Time frame: all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day.
vital parameters during HFOV-sigh vs HFOV-only
Time frame: all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christian Heiring, neonatologist principal investigator
Department of Neonatology, Rigshospitalet, Copenhagen
Luke Jardine, neonatologist principal investigator
Department of Neonatology, Mater Mothers Hospital, Brisbane, Australia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing HFOV combined with sigh breaths in people with Respiratory Distress Syndrome In Premature Infants and Bronchopulmonary Dysplasia, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Global changes in end expiratory lung volume (EELV) (time frame: all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2023.