Respiratory InsufficiencyThroughflowNCT05642832
Feasibility of Reducing Respiratory Drive Using the Through-flow System
A study testing Throughflow titration phase in people with Respiratory Insufficiency and Diaphragm Injury, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
Mechanical ventilation can lead to diaphragm and lung injury. During mechanical ventilation, the diaphragm could be completely rested or it could be overworked, either of which may cause diaphragm injury. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Respiratory Insufficiency, Diaphragm Injury, Lung Injury
- What is being tested?
- Throughflow titration phase
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteCanada
- Study dates
- 1 Jan 2024to 31 Aug 2025
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- PaO2/FiO2 less than or equal to 300 at time of screening
- Oral endotracheal intubation with ETT 7.5 or 8.0 and on invasive mechanical ventilation
- Bilateral airspace opacities on chest radiograph or chest CT scan
Who cannot join
- Contraindication to esophageal catheterization (upper gastrointestinal tract surgery within preceding 6 weeks, bleeding esophageal/gastric varices)
- Intubation for traumatic brain injury or stroke
- Intracranial hypertension (suspected or diagnosed by medical team)
- Anticipated liberation from mechanical ventilation within 24 hours
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
University Health Network
Toronto, Ontario, M5G 2N2
Cindy Jin, rongyu.jin@uhn.ca
About this study
Official title: Feasibility of Reducing Respiratory Drive in Patients with Acute Hypoxemic Respiratory Failure Using the Through-flow System
Mechanical ventilation can lead to diaphragm and lung injury. During mechanical ventilation, the diaphragm could be completely rested or it could be overworked, either of which may cause diaphragm injury. Mechanical stress and strain applied by mechanical ventilation or by the patient's own respiratory muscles can also cause injury to the lungs. Diaphragm and lung injury are associated with increased morbidity and mortality. Throughflow is a novel system that can reduce dead space without the need to increase the tidal ventilation, reducing the ventilatory demands and respiratory drive.
Read the detailed description
Patients with acute respiratory failure often develop significant diaphragm weakness during mechanical ventilation. Diaphragm weakness is associated with prolonged duration of mechanical ventilation and higher risk of death. Clinical data and experimental evidence indicate that the ventilator injures the diaphragm via two opposing mechanisms, disuse and excessive loading. Cessation of diaphragm activity leads to rapid disuse atrophy within hours. On the other hand, high inspiratory loads result in myofibril edema, inflammation and contractile dysfunction. In light of this, studies found that patients with an intermediate level of inspiratory effort, similar to that of healthy subjects breathing at rest, exhibited the shortest duration of ventilation.
Arterial CO2 (PaCO2) tension and physiological dead space play an important role in determining the ventilatory requirements and respiratory drive in patients with AHRF.
Throughflow (Neurovent) is a novel system that reduces anatomical dead space by providing a constant flow of fresh gas (i.e., gas that is free of CO2) during inspiration in patients receiving invasive mechanical ventilation. By clearing the CO2 that normally remains in the upper airway after exhalation (anatomical dead space), TF can dramatically reduce anatomical dead space without the need to increase the delivered VT.
Reducing dead space offers a theoretical benefit in mitigating the mechanisms of lung and diaphragm injury during spontaneous breathing by reducing the ventilation demands to the lungs. Animal studies using the TF have shown extremely promising results, however, the impact of reducing anatomical dead space using the TF on gas exchange, ventilation, and respiratory drive in critically ill patients with AHRF is unknown.
- Conditions
- Respiratory Insufficiency, Diaphragm Injury, Lung Injury
- Being tested
- Throughflow titration phase
- Medical subject headings
- Respiratory Insufficiency, Lung Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Throughflow titration phaseDevice
Ventilation will be applied in the TF mode with TF set to 0 LPM for 10 minutes. Patients will receive assist through the NAVA line of the tri-piece (NAVA set to similar settings as Servo period, ~60-80 LPM flow). Ventilation with Throughflow will be started at a TF flow of 5 LPM, and the NAVA flow will be reduced by 5 LPM. After 10 minutes measurements will be collected. If Edi is greater than or equal to 4 µV, TF flow will be increased to 10 LPM and NAVA flow will be adjusted to keep total flow constant. Measurements will be collected again after 10 minutes. TF flow will be increased in steps of 5 LPM and measurements collected every 10 minutes until Edi is below 3 µV or TF flow reaches the total flow observed during the NAVA period.
After either the Edi target has been met or TF flow has reached the total flow, ventilation with TF will be reduced in steps of 5 LPM every 10 minutes (the reverse of the above), while NAVA flow is accordingly adjusted to keep total flow constant.
| Study group | Role | What they receive |
|---|---|---|
| Throughflow | Experimental | Throughflow is a novel system that reduces anatomical dead space by providing a constant flow of fresh gas (i.e., gas that is free of CO2) during inspiration in patients receiving invasive mechanical ventilation. By clearing the CO2 that normally remains in the upper airway after exhalation (anatomical dead space), TF can dramatically reduce anatomical dead space without the need to increase the delivered VT, making it a safe strategy in terms of lung protection. This reduction in dead space reduces the ventilatory demands of the patients, reducing respiratory drive. Receives: Device: Throughflow titration phase |
What is being measured
The primary outcome is the main question the study is designed to answer.
Esophageal pressure swing (respiratory effort)
Changes in esophageal pressure swing from baseline to protocol completion will be described using central tendency and dispersion measurements (median and 25%-75% interquartile range) for each variable at each time point of the protocol
Measured: 24 hours
Dynamic driving transpulmonary pressure (lung-distending pressure)
Changes in the dynamic driving transpulmonary pressure from baseline to protocol completion will be described using central tendency and dispersion measurements (median and 25%-75% interquartile range) for each variable at each time point of the protocol
Measured: 24 hours
Oxygenation (PaO2/FiO2 ratio)
Changes in PaO2/FiO2 from baseline to protocol completion will be described using central tendency and dispersion measurements (median and 25%-75% interquartile range) for each variable at each time point of the protocol
Measured: 24 hours
Secondary outcomes (1)
Rate of serious adverse events
The number of SAEs during the protocol will be measured and quantified.
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2022
- Study start1 Jan 2024
- Primary completion30 Jun 2025 (estimated)
- Study completion31 Aug 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Respiratory InsufficiencyStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe 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
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Unity Health Toronto
- Responsible party
- Sponsor
- Investigators
- Ewan Goligher, MD, PhD, Principal investigator, University Health Network, TorontoLorenzo Del Sorbo, Principal investigator, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05642832
- Sponsor's protocol ID
- 21-5534
- Acronym
- Throughflow
- Status last verified
- Dec 2024
- First submitted
- 14 Jul 2022
- Last updated
- 11 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Feasibility of Reducing Respiratory Drive in Patients with Acute Hypoxemic Respiratory Failure Using the Through-flow System
- ClinicalTrials.gov ID
- NCT05642832
- Acronym / sponsor ID
- Throughflow / 21-5534
- Conditions
- Respiratory Insufficiency, Diaphragm Injury, Lung Injury
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- Unity Health Toronto
- Study start
- 1 Jan 2024 (actual)
- Primary completion
- 30 Jun 2025 (estimated)
- Study completion
- 31 Aug 2025 (estimated)
- First posted
- 8 Dec 2022 (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 can lead to diaphragm and lung injury. During mechanical ventilation, the diaphragm could be completely rested or it could be overworked, either of which may cause diaphragm injury. Mechanical stress and strain applied by mechanical ventilation or by the patient's own respiratory muscles can also cause injury to the lungs. Diaphragm and lung injury are associated with increased morbidity and mortality. Throughflow is a novel system that can reduce dead space without the need to increase the tidal ventilation, reducing the ventilatory demands and respiratory drive.
Detailed description
Patients with acute respiratory failure often develop significant diaphragm weakness during mechanical ventilation. Diaphragm weakness is associated with prolonged duration of mechanical ventilation and higher risk of death. Clinical data and experimental evidence indicate that the ventilator injures the diaphragm via two opposing mechanisms, disuse and excessive loading. Cessation of diaphragm activity leads to rapid disuse atrophy within hours. On the other hand, high inspiratory loads result in myofibril edema, inflammation and contractile dysfunction. In light of this, studies found that patients with an intermediate level of inspiratory effort, similar to that of healthy subjects breathing at rest, exhibited the shortest duration of ventilation.
Arterial CO2 (PaCO2) tension and physiological dead space play an important role in determining the ventilatory requirements and respiratory drive in patients with AHRF.
Throughflow (Neurovent) is a novel system that reduces anatomical dead space by providing a constant flow of fresh gas (i.e., gas that is free of CO2) during inspiration in patients receiving invasive mechanical ventilation. By clearing the CO2 that normally remains in the upper airway after exhalation (anatomical dead space), TF can dramatically reduce anatomical dead space without the need to increase the delivered VT.
Reducing dead space offers a theoretical benefit in mitigating the mechanisms of lung and diaphragm injury during spontaneous breathing by reducing the ventilation demands to the lungs. Animal studies using the TF have shown extremely promising results, however, the impact of reducing anatomical dead space using the TF on gas exchange, ventilation, and respiratory drive in critically ill patients with AHRF is unknown.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Throughflow | Experimental | Device: Throughflow titration phaseThroughflow is a novel system that reduces anatomical dead space by providing a constant flow of fresh gas (i.e., gas that is free of CO2) during inspiration in patients receiving invasive mechanical ventilation. By clearing the CO2 that normally remains in the upper airway after exhalation (anatomical dead space), TF can dramatically reduce anatomical dead space without the need to increase the delivered VT, making it a safe strategy in terms of lung protection. This reduction in dead space reduces the ventilatory demands of the patients, reducing respiratory drive. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- PaO2/FiO2 less than or equal to 300 at time of screening
- Oral endotracheal intubation with ETT 7.5 or 8.0 and on invasive mechanical ventilation
- Bilateral airspace opacities on chest radiograph or chest CT scan
Key exclusion criteria (4 listed)
- Contraindication to esophageal catheterization (upper gastrointestinal tract surgery within preceding 6 weeks, bleeding esophageal/gastric varices)
- Intubation for traumatic brain injury or stroke
- Intracranial hypertension (suspected or diagnosed by medical team)
- Anticipated liberation from mechanical ventilation within 24 hours
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 |
|---|---|---|
| Throughflow titration phaseVentilation will be applied in the TF mode with TF set to 0 LPM for 10 minutes. Patients will receive assist through the NAVA line of the tri-piece (NAVA set to similar settings as Servo period, ~60-80 LPM flow). Ventilation with Throughflow will be started at a TF flow of 5 LPM, and the NAVA flow will be reduced by 5 LPM. After 10 minutes measurements will be collected. If Edi is greater than or equal to 4 µV, TF flow will be increased to 10 LPM and NAVA flow will be adjusted to keep total flow constant. Measurements will be collected again after 10 minutes. TF flow will be increased in steps of 5 LPM and measurements collected every 10 minutes until Edi is below 3 µV or TF flow reaches the total flow observed during the NAVA period. After either the Edi target has been met or TF flow has reached the total flow, ventilation with TF will be reduced in steps of 5 LPM every 10 minutes (the reverse of the above), while NAVA flow is accordingly adjusted to keep total flow constant. | Device | Throughflow |
Primary outcome
Esophageal pressure swing (respiratory effort)
Time frame: 24 hours
Changes in esophageal pressure swing from baseline to protocol completion will be described using central tendency and dispersion measurements (median and 25%-75% interquartile range) for each variable at each time point of the protocol
Dynamic driving transpulmonary pressure (lung-distending pressure)
Time frame: 24 hours
Changes in the dynamic driving transpulmonary pressure from baseline to protocol completion will be described using central tendency and dispersion measurements (median and 25%-75% interquartile range) for each variable at each time point of the protocol
Oxygenation (PaO2/FiO2 ratio)
Time frame: 24 hours
Changes in PaO2/FiO2 from baseline to protocol completion will be described using central tendency and dispersion measurements (median and 25%-75% interquartile range) for each variable at each time point of the protocol
1 secondary outcome
Rate of serious adverse events
Time frame: 24 hours
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 11 Dec 2024.
- 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.
Ewan Goligher, MD, PhD principal investigator
University Health Network, Toronto
Lorenzo Del Sorbo principal investigator
University Health Network, Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Throughflow titration phase in people with Respiratory Insufficiency and Diaphragm Injury, run by University Health Network, Toronto at 1 site in Canada.
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 3 inclusion and 4 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 11 Dec 2024. 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 Canada. 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 Rongyu ( Cindy) Jin (4163404800 ext. 7613, rongyu.jin@uhn.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Esophageal pressure swing (respiratory effort) (time frame: 24 hours). The study lists 3 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 11 Dec 2024; AzTrials last refreshed its copy on 26 Oct 2026.