High Frequency OscillationNCT06719284
Optimising HFO&VTV in Newborn Infants
A study testing HFO&VTV at targeted tidal volumes of 1.5, 2.0 and 2.5 ml/kg in random order and HFOV at the settings applied prior to the study in people with High Frequency Oscillation and Volume Targeted Ventilation, run by King's College Hospital NHS Trust at 1 site in United Kingdom.
Trial summary
Mechanical ventilation (MV) is life saving for infants requiring respiratory support in the newborn period but its use has been associated with complications. High frequency oscillation (HFO) is a type of MV that delivers small volumes of gas across the lungs at fast frequencies. Read more about this study
- Who is it for?
- Ages 22 weeks to 1 year
- Conditions the study is for
- High Frequency Oscillation, Volume Targeted Ventilation
- What is being tested?
- HFO&VTV at targeted tidal volumes of 1.5, 2.0 and 2.5 ml/kg in random order and HFOV at the settings applied prior to the study
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 26 Feb 2025to 1 Sep 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 22 weeks to 1 year
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- -Newborn infants of any gestation receiving high frequency oscillatory ventilation
Who cannot join
- Infants with known intracerebral pathology (stroke, hydrocephalus, intracerebral hemorrhage, severe hypoxic ischemic encephalopathy).
- Infants with congenital cardiac abnormalities.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Theodore Dassios contact
United Kingdom1 site, 1 recruiting
- Recruiting
King's College Hospital
London, S£5 9RS
Ourania Kaltsogianni, MSc
About this study
Official title: Crossover Study of the Cerebral Blood Flow and Cardiac Output At Different Targeted Tidal Volumes During High Frequency Oscillation with Volume Targeted Ventilation (HFO&VTV)
Mechanical ventilation (MV) is life saving for infants requiring respiratory support in the newborn period but its use has been associated with complications. High frequency oscillation (HFO) is a type of MV that delivers small volumes of gas across the lungs at fast frequencies. HFO is a lung protective strategy but it has also been linked to brain injury due to low carbon dioxide tensions. High-frequency oscillation with volume-targeted ventilation (HFO\&VTV) is a new mode of HFO in which the clinician sets a target volume of gas to be delivered to the lungs at fast rates to decrease the lung injury related to the ventilator. Further, HFO\&VTV achieves better control of carbon dioxide levels and may therefore protect against brain injury. Currently, there are no written guidelines about the use of HFO\&VTV. This study aim to determine the safety profile of HFO\&VTV compared to HFO by comparing the velocity of blood flow to the brain in term born infants and the cardiac output in term and preterm infants during the two modes. The investigators will also determine the optimum starting value of the target tidal volume during HFOV\&VTV. Infants will be studied at three different target tidal volumes for a period of 10-20 minutes each. A cranial ultrasound (for term infants only) and bedside echocardiogram will be performed at the end of each period.
Read the detailed description
This is a single centre, randomised cross-over trial in newborn infants requiring high-frequency oscillatory ventilation (HFOV) at any postnatal age. Infants with known intracerebral pathology (stroke, hydrocephalus, intracerebral haemorrhage, severe HIE) and congenital cardiac abnormalities will be excluded from the study. In preterm infants cerebral blood flow will not be studied as there is no clear evidence for the significance of the resistive index (RI) in the cerebral arteries to predict brain injury and neurodevelopmental outcomes.
The research team will identify infants based on the inclusion criteria and approach parents to discuss the study and provide information leaflets.
The investigators aim to recruit a minimum of 25 infants (13 preterm and 12 term infants) over 18 months.
Informed written consent will be requested from the parents or legal guardians of the infants and the attending Neonatal Consultant will be requested to verbally assent to the study.
All infants will be oscillated using SLE6000 ventilators. Ventilation settings will be adjusted by the clinical team as per unit's protocol.
Infants will be studied when clinically stable and a blood gas confirms that the carbon dioxide (CO2) levels are in the target range (4.5 to 6.5 kPa). Participants will receive HFO\&VTV at targeted tidal volumes of 1.5, 2.0 and 2.5 ml/kg in random order for a period of 10-20 minutes each. Additionally, there will be a control period of 20 minutes between each tidal volume when infants will be switched to HFOV without volume-guarantee at the settings applied prior to the study. The order in which they receive the different levels of tidal volumes will be randomised using an excel random number generator.
Transcutaneous CO2 monitoring will be applied to the infants during the study. The resistive index (RI) as an indicator of cerebral blood flow in term infants and the cardiac output of all paticipants will be assessed at the last five minutes of each twenty-minute period. Measurements of the RI and the cardiac output will also be made during the last five minutes of the control periods and the results will be averaged.
The nurse to patient ration will be according to the unit's protocol that is determined on the patient's acuity.
The investigators will also record basic epidemiologic parameters such as sex, gestational age, birth weight, mode of delivery, Apgar scores, administration of surfactant, day of life at study, mechanical ventilation starting time and HFO starting time, and initial diagnosis.
- Being tested
- HFO&VTV at targeted tidal volumes of 1.5, 2.0 and 2.5 ml/kg in random order, HFOV at the settings applied prior to the study
- Keywords
- high frequency oscillation, volume targeted ventilation, newborn infant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HFO&VTV at targeted tidal volumes of 1.5, 2.0 and 2.5 ml/kg in random orderOther
HFO\&VTV at targeted tidal volumes of 1.5, 2.0 and 2.5 ml/kg in random order
HFOV at the settings applied prior to the studyOther
HFOV at the settings applied prior to the study
| Study group | Role | What they receive |
|---|---|---|
| High frequency oscillation at the settings applied prior to the study | Active comparator | Not described Receives: Other: HFOV at the settings applied prior to the study |
| High frequency oscillation with volume targeted ventilation | Active comparator | Not described Receives: Other: HFO&VTV at targeted tidal volumes of 1.5, 2.0 and 2.5 ml/kg in random order |
What is being measured
The primary outcome is the main question the study is designed to answer.
The change in the Resistive Index (RI) that will be measured on term born infants using the anterior cerebral artery Doppler on cranial ultrasound
Measured: Through study completion, an average of 18 months
Secondary outcomes (1)
The change in cardiac output that will be assessed with bedside ECHO in all infants
Measured: Through study completion, an average of 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2024
- Study start26 Feb 2025
- Primary completion1 Sep 2026 (estimated)
- Study completion1 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for High Frequency OscillationStudies of the same condition, open and under way.
- More trials run by King's College Hospital NHS TrustThe 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
- 27 participants (estimated)
Sponsor and investigators
- Lead sponsor
- King's College Hospital NHS Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Theodore Dassios, Professor, Principal investigator, King's College Hospital NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06719284
- Sponsor's protocol ID
- 349734
- Status last verified
- Mar 2025
- First submitted
- 26 Nov 2024
- Last updated
- 10 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Camfferman FA, de Goederen R, Govaert P, Dudink J, van Bel F, Pellicer A, Cools F; eurUS.brain group. Diagnostic and predictive value of Doppler ultrasound for evaluation of the brain circulation in preterm infants: a systematic review. Pediatr Res. 2020 Mar;87(Suppl 1):50-58. doi: 10.1038/s41390-020-0777-x.
PubMed 32218536Tuzun F, Deliloglu B, Cengiz MM, Iscan B, Duman N, Ozkan H. Volume Guarantee High-Frequency Oscillatory Ventilation in Preterm Infants With RDS: Tidal Volume and DCO2 Levels for Optimal Ventilation Using Open-Lung Strategies. Front Pediatr. 2020 Mar 24;8:105. doi: 10.3389/fped.2020.00105. eCollection 2020.
PubMed 32266185Iscan B, Duman N, Tuzun F, Kumral A, Ozkan H. Impact of Volume Guarantee on High-Frequency Oscillatory Ventilation in Preterm Infants: A Randomized Crossover Clinical Trial. Neonatology. 2015;108(4):277-82. doi: 10.1159/000437204. Epub 2015 Sep 1.
PubMed 26330156Kaltsogianni O, Nanjundappa M, Okoye G, Greenough A, Dassios T. Effect of different targeted tidal volumes during high-frequency oscillation with volume-targeted ventilation on cerebral blood flow velocity and cardiac output: study protocol for a randomised crossover study. Trials. 2025 Oct 22;26(1):427. doi: 10.1186/s13063-025-09179-w.
PubMed 41126304
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Crossover Study of the Cerebral Blood Flow and Cardiac Output At Different Targeted Tidal Volumes During High Frequency Oscillation with Volume Targeted Ventilation (HFO&VTV)
- ClinicalTrials.gov ID
- NCT06719284
- Acronym / sponsor ID
- 349734
- Keywords
- high frequency oscillation, volume targeted ventilation, newborn infant
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 27 participants (estimated)
- Lead sponsor
- King's College Hospital NHS TrustUniversity, hospital or other
- Study start
- 26 Feb 2025 (actual)
- Primary completion
- 1 Sep 2026 (estimated)
- Study completion
- 1 Sep 2026 (estimated)
- First posted
- 5 Dec 2024 (actual)
- 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.
Mechanical ventilation (MV) is life saving for infants requiring respiratory support in the newborn period but its use has been associated with complications. High frequency oscillation (HFO) is a type of MV that delivers small volumes of gas across the lungs at fast frequencies. HFO is a lung protective strategy but it has also been linked to brain injury due to low carbon dioxide tensions. High-frequency oscillation with volume-targeted ventilation (HFO\&VTV) is a new mode of HFO in which the clinician sets a target volume of gas to be delivered to the lungs at fast rates to decrease the lung injury related to the ventilator. Further, HFO\&VTV achieves better control of carbon dioxide levels and may therefore protect against brain injury. Currently, there are no written guidelines about the use of HFO\&VTV. This study aim to determine the safety profile of HFO\&VTV compared to HFO by comparing the velocity of blood flow to the brain in term born infants and the cardiac output in term and preterm infants during the two modes. The investigators will also determine the optimum starting value of the target tidal volume during HFOV\&VTV. Infants will be studied at three different target tidal volumes for a period of 10-20 minutes each. A cranial ultrasound (for term infants only) and bedside echocardiogram will be performed at the end of each period.
Detailed description
This is a single centre, randomised cross-over trial in newborn infants requiring high-frequency oscillatory ventilation (HFOV) at any postnatal age. Infants with known intracerebral pathology (stroke, hydrocephalus, intracerebral haemorrhage, severe HIE) and congenital cardiac abnormalities will be excluded from the study. In preterm infants cerebral blood flow will not be studied as there is no clear evidence for the significance of the resistive index (RI) in the cerebral arteries to predict brain injury and neurodevelopmental outcomes.
The research team will identify infants based on the inclusion criteria and approach parents to discuss the study and provide information leaflets.
The investigators aim to recruit a minimum of 25 infants (13 preterm and 12 term infants) over 18 months.
Informed written consent will be requested from the parents or legal guardians of the infants and the attending Neonatal Consultant will be requested to verbally assent to the study.
All infants will be oscillated using SLE6000 ventilators. Ventilation settings will be adjusted by the clinical team as per unit's protocol.
Infants will be studied when clinically stable and a blood gas confirms that the carbon dioxide (CO2) levels are in the target range (4.5 to 6.5 kPa). Participants will receive HFO\&VTV at targeted tidal volumes of 1.5, 2.0 and 2.5 ml/kg in random order for a period of 10-20 minutes each. Additionally, there will be a control period of 20 minutes between each tidal volume when infants will be switched to HFOV without volume-guarantee at the settings applied prior to the study. The order in which they receive the different levels of tidal volumes will be randomised using an excel random number generator.
Transcutaneous CO2 monitoring will be applied to the infants during the study. The resistive index (RI) as an indicator of cerebral blood flow in term infants and the cardiac output of all paticipants will be assessed at the last five minutes of each twenty-minute period. Measurements of the RI and the cardiac output will also be made during the last five minutes of the control periods and the results will be averaged.
The nurse to patient ration will be according to the unit's protocol that is determined on the patient's acuity.
The investigators will also record basic epidemiologic parameters such as sex, gestational age, birth weight, mode of delivery, Apgar scores, administration of surfactant, day of life at study, mechanical ventilation starting time and HFO starting time, and initial diagnosis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| High frequency oscillation at the settings applied prior to the study | Active comparator | Other: HFOV at the settings applied prior to the study |
| High frequency oscillation with volume targeted ventilation | Active comparator | Other: HFO&VTV at targeted tidal volumes of 1.5, 2.0 and 2.5 ml/kg in random order |
Who may qualify
- Ages
- 22 weeks to 1 year
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- -Newborn infants of any gestation receiving high frequency oscillatory ventilation
Key exclusion criteria (2 listed)
- Infants with known intracerebral pathology (stroke, hydrocephalus, intracerebral hemorrhage, severe hypoxic ischemic encephalopathy).
- Infants with congenital cardiac abnormalities.
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 |
|---|---|---|
| HFO&VTV at targeted tidal volumes of 1.5, 2.0 and 2.5 ml/kg in random orderHFO\&VTV at targeted tidal volumes of 1.5, 2.0 and 2.5 ml/kg in random order | Other | High frequency oscillation with volume targeted ventilation |
| HFOV at the settings applied prior to the studyHFOV at the settings applied prior to the study | Other | High frequency oscillation at the settings applied prior to the study |
Primary outcome
The change in the Resistive Index (RI) that will be measured on term born infants using the anterior cerebral artery Doppler on cranial ultrasound
Time frame: Through study completion, an average of 18 months
1 secondary outcome
The change in cardiac output that will be assessed with bedside ECHO in all infants
Time frame: Through study completion, an average of 18 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2025.
- Background: PubMed 32218536Camfferman FA, de Goederen R, Govaert P, Dudink J, van Bel F, Pellicer A, Cools F; eurUS.brain group. Diagnostic and predictive value of Doppler ultrasound for evaluation of the brain circulation in preterm infants: a systematic review. Pediatr Res. 2020 Mar;87(Suppl 1):50-58. doi: 10.1038/s41390-020-0777-x.
- Background: PubMed 32266185Tuzun F, Deliloglu B, Cengiz MM, Iscan B, Duman N, Ozkan H. Volume Guarantee High-Frequency Oscillatory Ventilation in Preterm Infants With RDS: Tidal Volume and DCO2 Levels for Optimal Ventilation Using Open-Lung Strategies. Front Pediatr. 2020 Mar 24;8:105. doi: 10.3389/fped.2020.00105. eCollection 2020.
- Background: PubMed 26330156Iscan B, Duman N, Tuzun F, Kumral A, Ozkan H. Impact of Volume Guarantee on High-Frequency Oscillatory Ventilation in Preterm Infants: A Randomized Crossover Clinical Trial. Neonatology. 2015;108(4):277-82. doi: 10.1159/000437204. Epub 2015 Sep 1.
- Derived from this study: PubMed 41126304Kaltsogianni O, Nanjundappa M, Okoye G, Greenough A, Dassios T. Effect of different targeted tidal volumes during high-frequency oscillation with volume-targeted ventilation on cerebral blood flow velocity and cardiac output: study protocol for a randomised crossover study. Trials. 2025 Oct 22;26(1):427. doi: 10.1186/s13063-025-09179-w.
- Individual participant dataSharing planned: No
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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.
Theodore Dassios contact
Theodore Dassios, Professor principal investigator
King's College Hospital NHS Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing HFO&VTV at targeted tidal volumes of 1.5, 2.0 and 2.5 ml/kg in random order and HFOV at the settings applied prior to the study in people with High Frequency Oscillation and Volume Targeted Ventilation, run by King's College Hospital NHS Trust at 1 site in United Kingdom.
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 1 inclusion and 2 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: looking for participants now, as of the sponsor's last update on 10 Mar 2025. 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 United Kingdom. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ourania Kaltsogianni, MSc (0044+02032999000, ourania.kaltsogianni@nhs.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The change in the Resistive Index (RI) that will be measured on term born infants using the anterior cerebral artery Doppler on cranial ultrasound (time frame: Through study completion, an average of 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06719284, which also lists 4 linked publications.
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 10 Mar 2025.