Respiration, ArtificialSEVERENCT06293976
Susceptibility for Entrainment: Role of Ventilator Settings on the Occurrence of Reverse Triggering and Its Physiological Consequences - the SEVeRe Study
A study testing Changes in the ventilator respiratory rate and tidal volume in people with Respiration, Artificial and Reverse Triggering, run by Unity Health Toronto at 1 site in Canada.
Trial summary
Background: Reverse triggering (RT) is a frequent phenomenon observed in sedated patients under a mechanical ventilation mode called assist-control ventilation. RT is when the ventilator would trigger the patient's respiratory effort instead of the correct order of the patient's respiratory effort triggering the… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Respiration, Artificial, Reverse Triggering
- What is being tested?
- Changes in the ventilator respiratory rate and tidal volume
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteCanada
- Study dates
- 30 Jan 2025to 1 Mar 2026
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients intubated for more than 12 hours
- On assist-control ventilation, not triggering the ventilator
- Exposed to sedation for at least 6 hours
- With a sedation-agitation score ≤ 4.
Who cannot join
- primary severe neurological disorders
- previous lung transplant
- contraindications for esophageal catheter insertion
- current use of continuous neuromuscular blocking agents at the time of the study procedure
- severe metabolic acidosis (pH < 7.25) at the time of study procedure.
Trial locations and contacts
1 site in 1 country.
Irene Telias contact
Canada1 site, 1 recruiting
- Recruiting
Unity Health Toronto - St. Michael's Hospital
Toronto, Ontario, M5B 1T8
Audery Kim, 416-864-5686, audery.kim@unityhealth.to
Antenor Rodrigues
About this study
Background: Reverse triggering (RT) is a frequent phenomenon observed in sedated patients under a mechanical ventilation mode called assist-control ventilation. RT is when the ventilator would trigger the patient's respiratory effort instead of the correct order of the patient's respiratory effort triggering the ventilator. Reverse triggering can have negative consequences (loss of protective lung ventilation, and causing double breaths - with the ventilator giving two consecutive breaths and not allowing the patient to exhale) but also offer some protective effects (avoid diaphragm disuse atrophy). The balance of its negative vs positive effects depends on its frequency and magnitude of its associated respiratory effort. Respiratory entrainment is the most often referred mechanism involving a change in patient's rate of breathing effort from that of patient's intrinsic rate to the rate of mechanical insufflation. The specific ventilatory settings associated with or responsible for RT remains unknown.
Aims: To assess in mechanically ventilated critically ill patients the influence of the set respiratory rate (RR) and tidal volume (Vt) on the presence/development of RT and to describe the pattern of respiratory muscle activity during Reverse Triggering (RT).
Methods. 30 adult patients (15 in each group), sedated and under assist-controlled ventilation will be included. Ventilator settings will be modified to modulate the frequency and magnitude of reverse triggering. Initially, with the ventilator on a mode called volume control, which means the ventilator controls the amount of air (tidal volume) and the number of breaths the patients gets every minute (respiratory rate [RR]). The tidal volume will be set at the current standard clinical practice setting (6 ml/kg of predicted body weight). The presence of an intrinsic respiratory rate will be assessed with an end-expiratory occlusion maneuver. Next, the number of breaths the ventilator gives per minute (RR) will be changed from 6 breaths less to 6 breaths more, in steps of 2 breaths every minute. The protocol will be repeated again changing the amount of air the patients gets (tidal volume) from 4, 5, 7 and 8 ml/kg. Continuous recordings of airway pressure, flow, esophageal pressure, electrical activity of the diaphragm, main accessory muscles and frontal electroencephalography will be obtained during the protocol and baseline clinical and physiological characteristics and outcomes will be recorded. A validated software will be used to detect RT and measure the intensity and timing of each muscle electrical activity and the magnitude of the inspiratory effort during RT.
Read the detailed description
Participants. Critically ill patients (n: 30; aimed recruitment of equal numbers of men and women) aged 18 years or older admitted to the St. Michael's Hospital, Unity Health Toronto, Ontario, Canada.
Inclusion criteria:
- patients intubated for more than 12 hours
- exposed to sedation for at least 6 hours
- with a sedation-agitation score ≤ 4
- and corresponding to one of the following categories based on bedside inspection of ventilator waveforms:
- patients on assist-control ventilation having reverse triggering at clinical settings (n: 15).
- patients on assist-control ventilation without reverse triggering at the clinical settings (n: 15).
Exclusion criteria:
- primary severe neurological disorders
- previous lung transplant
- contraindications for esophageal catheter insertion
- current use of continuous neuromuscular blocking agents at the time of the study procedure
- severe metabolic acidosis (pH < 7.25) at the time of study procedure. Study design. Briefly, first the ventilator Vt is set at 6 ml/kg of predicted body weight (PBW) (i.e., clinical practice recommendation) and either a up to 30sec-long (or two inspiratory efforts) end-expiratory occlusion maneuver will be performed on the ventilator or the patient will be switched to pressure support for 30 - 60 sec (based on discussion with the clinical team) to assess the presence or absence of patient's intrinsic RR.
Secondly, the influence of the ventilator RR on both the occurrence of reverse triggering and the level of effort associated with the reverse triggered breath will be assessed. In random order the ventilator RR will be modified from 6 bpm below up to 6 bpm above the clinical RR in steps of 2 bpm every 1 minute (Figure 1). A 1-minute stage at the patients clinical settings of ventilation in-between each step will be performed to minimize changes in PaCO2.
Thirdly, the influence of the Vt set on the ventilator on both the occurrence of reverse triggering and the level of effort associated with the reverse triggered breath will be assessed. The ventilator Vt will be set to 5 ml/kg PBW, 7 and 8 ml/kg PBW in random order and for each volume, repeat the sequence described in the paragraph above. A 1-minute clinical settings ventilation will be performed in-between each step to minimize changes in PaCO2.
Next, the patient will be returned to their initial clinical settings. Another end-expiratory occlusion of up to 30 seconds (or two inspiratory efforts) or switch the patient to pressure support for 30 - 60 sec (based on discussion with the clinical team) will be performed to search for an intrinsic RR (i.e., intrinsic respiratory drive). If an intrinsic respiratory rate ≥8 breaths per minute is present and P/F ratio is ≥150, it will propose to the clinician to place the patient in pressure support at a level preferred by clinicians for 5 minutes. If the patient tolerates well 5 minutes in pressure support, it be will propose to the clinician to maintain the patient in pressure support ventilation.
The steps described above will be aborted at any point if SpO2 drops below 85% for at least two minutes, mean arterial pressure drops below 60 mmHg, or plateau pressure >35 cmH2O.
Additionally, the ventilator waveforms and electroencephalography (EEG) will be recorded continuously for the next 24 hours to investigate whether the presence of intrinsic RR was associated with changes in the ventilation mode by the clinician and brain activity.
- Conditions
- Respiration, Artificial, Reverse Triggering
- Being tested
- Changes in the ventilator respiratory rate and tidal volume
- Keywords
- Hypnotics and Sedatives, Respiratory Muscles
- Medical subject headings
- Respiratory Aspiration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Changes in the ventilator respiratory rate and tidal volumeOther
With the ventilator on volume control and Vt at 6 ml/kg of predicted body weight (PBW) (standard clinical practice), an end-expiratory occlusion of 30 seconds on the ventilator will be performed to search for intrinsic respiratory rate (RR). The set RR will be modified from 6 breaths per minute (bpm) below up to 6 bpm above the clinical RR in steps of 2 bpm every 1 minute (random order). The changes in RR described above will be repeated with Vt set at 5, 7 and 8 ml/kg PBW (random order). The steps described above will be aborted at any point if SpO2 drops below 85% for at least two minutes, mean arterial pressure drops below 60 mmHg, or plateau pressure >35 cmH2O.
If an intrinsic respiratory rate ≥8 bpm is present and P/F ratio is ≥150, it will be propose to the clinician to place the patient in pressure support at a level preferred by clinicians for 5 minutes. If the patient tolerates well, it will be propose to the clinician to maintain the patient in pressure support ventilation,
| Study group | Role | What they receive |
|---|---|---|
| Patients under mechanical ventilation | Experimental | Patients intubated for more than 12 hours, on assist-control ventilation, not triggering the ventilator with or without reverse triggering, exposed to sedation for at least 6 hours, with a sedation-agitation score ≤ 4. Receives: Other: Changes in the ventilator respiratory rate and tidal volume |
What is being measured
The primary outcome is the main question the study is designed to answer.
The rate of of reverse triggered breaths occurring after each change in the ventilator respiratory rate and tidal volume.
The rate of reverse triggered breaths occurring after each change in the ventilator respiratory rate and tidal volume.
Measured: 1 minutes
The magnitude of the effort, measured by the drop in the esophageal pressure in cmH2O, associated with the reverse triggered breaths after each change in the ventilator respiratory rate and tidal volume
The magnitude of the effort, measured by the drop in the esophageal pressure in cmH2O, associated with the reverse triggered breaths after each change in the ventilator respiratory rate and tidal volume
Measured: 1 minute
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2024
- Study start30 Jan 2025
- Primary completion1 Mar 2026 (estimated)
- Study completion1 Mar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Respiration, ArtificialStudies of the same condition, open and under way.
- More trials run by Unity Health 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
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Unity Health Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Laurent Brochard, Principal investigator, Unity Health Toronto - St. Michael's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06293976
- Sponsor's protocol ID
- 4506
- Acronym
- SEVERE
- Status last verified
- May 2024
- First submitted
- 20 Feb 2024
- Last updated
- 20 May 2025
- 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 20 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Susceptibility for Entrainment: Role of Ventilator Settings on the Occurrence of Reverse Triggering and Its Physiological Consequences - the SEVeRe Study
- ClinicalTrials.gov ID
- NCT06293976
- Acronym / sponsor ID
- SEVERE / 4506
- Conditions
- Respiration, Artificial, Reverse Triggering
- Keywords
- Hypnotics and Sedatives, Respiratory Muscles
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Unity Health TorontoUniversity, hospital or other
- Study start
- 30 Jan 2025 (actual)
- Primary completion
- 1 Mar 2026 (estimated)
- Study completion
- 1 Mar 2026 (estimated)
- First posted
- 5 Mar 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.
Background: Reverse triggering (RT) is a frequent phenomenon observed in sedated patients under a mechanical ventilation mode called assist-control ventilation. RT is when the ventilator would trigger the patient's respiratory effort instead of the correct order of the patient's respiratory effort triggering the ventilator. Reverse triggering can have negative consequences (loss of protective lung ventilation, and causing double breaths - with the ventilator giving two consecutive breaths and not allowing the patient to exhale) but also offer some protective effects (avoid diaphragm disuse atrophy). The balance of its negative vs positive effects depends on its frequency and magnitude of its associated respiratory effort. Respiratory entrainment is the most often referred mechanism involving a change in patient's rate of breathing effort from that of patient's intrinsic rate to the rate of mechanical insufflation. The specific ventilatory settings associated with or responsible for RT remains unknown.
Aims: To assess in mechanically ventilated critically ill patients the influence of the set respiratory rate (RR) and tidal volume (Vt) on the presence/development of RT and to describe the pattern of respiratory muscle activity during Reverse Triggering (RT).
Methods. 30 adult patients (15 in each group), sedated and under assist-controlled ventilation will be included. Ventilator settings will be modified to modulate the frequency and magnitude of reverse triggering. Initially, with the ventilator on a mode called volume control, which means the ventilator controls the amount of air (tidal volume) and the number of breaths the patients gets every minute (respiratory rate [RR]). The tidal volume will be set at the current standard clinical practice setting (6 ml/kg of predicted body weight). The presence of an intrinsic respiratory rate will be assessed with an end-expiratory occlusion maneuver. Next, the number of breaths the ventilator gives per minute (RR) will be changed from 6 breaths less to 6 breaths more, in steps of 2 breaths every minute. The protocol will be repeated again changing the amount of air the patients gets (tidal volume) from 4, 5, 7 and 8 ml/kg. Continuous recordings of airway pressure, flow, esophageal pressure, electrical activity of the diaphragm, main accessory muscles and frontal electroencephalography will be obtained during the protocol and baseline clinical and physiological characteristics and outcomes will be recorded. A validated software will be used to detect RT and measure the intensity and timing of each muscle electrical activity and the magnitude of the inspiratory effort during RT.
Detailed description
Participants. Critically ill patients (n: 30; aimed recruitment of equal numbers of men and women) aged 18 years or older admitted to the St. Michael's Hospital, Unity Health Toronto, Ontario, Canada.
Inclusion criteria:
- patients intubated for more than 12 hours
- exposed to sedation for at least 6 hours
- with a sedation-agitation score ≤ 4
- and corresponding to one of the following categories based on bedside inspection of ventilator waveforms:
- patients on assist-control ventilation having reverse triggering at clinical settings (n: 15).
- patients on assist-control ventilation without reverse triggering at the clinical settings (n: 15).
Exclusion criteria:
- primary severe neurological disorders
- previous lung transplant
- contraindications for esophageal catheter insertion
- current use of continuous neuromuscular blocking agents at the time of the study procedure
- severe metabolic acidosis (pH < 7.25) at the time of study procedure. Study design. Briefly, first the ventilator Vt is set at 6 ml/kg of predicted body weight (PBW) (i.e., clinical practice recommendation) and either a up to 30sec-long (or two inspiratory efforts) end-expiratory occlusion maneuver will be performed on the ventilator or the patient will be switched to pressure support for 30 - 60 sec (based on discussion with the clinical team) to assess the presence or absence of patient's intrinsic RR.
Secondly, the influence of the ventilator RR on both the occurrence of reverse triggering and the level of effort associated with the reverse triggered breath will be assessed. In random order the ventilator RR will be modified from 6 bpm below up to 6 bpm above the clinical RR in steps of 2 bpm every 1 minute (Figure 1). A 1-minute stage at the patients clinical settings of ventilation in-between each step will be performed to minimize changes in PaCO2.
Thirdly, the influence of the Vt set on the ventilator on both the occurrence of reverse triggering and the level of effort associated with the reverse triggered breath will be assessed. The ventilator Vt will be set to 5 ml/kg PBW, 7 and 8 ml/kg PBW in random order and for each volume, repeat the sequence described in the paragraph above. A 1-minute clinical settings ventilation will be performed in-between each step to minimize changes in PaCO2.
Next, the patient will be returned to their initial clinical settings. Another end-expiratory occlusion of up to 30 seconds (or two inspiratory efforts) or switch the patient to pressure support for 30 - 60 sec (based on discussion with the clinical team) will be performed to search for an intrinsic RR (i.e., intrinsic respiratory drive). If an intrinsic respiratory rate ≥8 breaths per minute is present and P/F ratio is ≥150, it will propose to the clinician to place the patient in pressure support at a level preferred by clinicians for 5 minutes. If the patient tolerates well 5 minutes in pressure support, it be will propose to the clinician to maintain the patient in pressure support ventilation.
The steps described above will be aborted at any point if SpO2 drops below 85% for at least two minutes, mean arterial pressure drops below 60 mmHg, or plateau pressure >35 cmH2O.
Additionally, the ventilator waveforms and electroencephalography (EEG) will be recorded continuously for the next 24 hours to investigate whether the presence of intrinsic RR was associated with changes in the ventilation mode by the clinician and brain activity.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients under mechanical ventilation | Experimental | Other: Changes in the ventilator respiratory rate and tidal volumePatients intubated for more than 12 hours, on assist-control ventilation, not triggering the ventilator with or without reverse triggering, exposed to sedation for at least 6 hours, with a sedation-agitation score ≤ 4. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients intubated for more than 12 hours
- On assist-control ventilation, not triggering the ventilator
- Exposed to sedation for at least 6 hours
- With a sedation-agitation score ≤ 4.
Key exclusion criteria (5 listed)
- primary severe neurological disorders
- previous lung transplant
- contraindications for esophageal catheter insertion
- current use of continuous neuromuscular blocking agents at the time of the study procedure
- severe metabolic acidosis (pH < 7.25) at the time of study procedure.
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 |
|---|---|---|
| Changes in the ventilator respiratory rate and tidal volumeWith the ventilator on volume control and Vt at 6 ml/kg of predicted body weight (PBW) (standard clinical practice), an end-expiratory occlusion of 30 seconds on the ventilator will be performed to search for intrinsic respiratory rate (RR). The set RR will be modified from 6 breaths per minute (bpm) below up to 6 bpm above the clinical RR in steps of 2 bpm every 1 minute (random order). The changes in RR described above will be repeated with Vt set at 5, 7 and 8 ml/kg PBW (random order). The steps described above will be aborted at any point if SpO2 drops below 85% for at least two minutes, mean arterial pressure drops below 60 mmHg, or plateau pressure >35 cmH2O. If an intrinsic respiratory rate ≥8 bpm is present and P/F ratio is ≥150, it will be propose to the clinician to place the patient in pressure support at a level preferred by clinicians for 5 minutes. If the patient tolerates well, it will be propose to the clinician to maintain the patient in pressure support ventilation, | Other | Patients under mechanical ventilation |
Primary outcome
The rate of of reverse triggered breaths occurring after each change in the ventilator respiratory rate and tidal volume.
Time frame: 1 minutes
The rate of reverse triggered breaths occurring after each change in the ventilator respiratory rate and tidal volume.
The magnitude of the effort, measured by the drop in the esophageal pressure in cmH2O, associated with the reverse triggered breaths after each change in the ventilator respiratory rate and tidal volume
Time frame: 1 minute
The magnitude of the effort, measured by the drop in the esophageal pressure in cmH2O, associated with the reverse triggered breaths after each change in the ventilator respiratory rate and tidal volume
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2025.
- 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. This study is not recruiting at the moment.
Irene Telias contact
Laurent Brochard principal investigator
Unity Health Toronto - St. Michael's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Changes in the ventilator respiratory rate and tidal volume in people with Respiration, Artificial and Reverse Triggering, run by Unity Health 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 4 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 20 May 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 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Antenor Rodrigues (416-864-5686, Antenor.Rodrigues@unityhealth.to), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The rate of of reverse triggered breaths occurring after each change in the ventilator respiratory rate and tidal volume. (time frame: 1 minutes). 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 20 May 2025.