Respiratory FailureVARIATIONNCT07518862
Heart Rate VAriability as a MaRker for tItrATing hIgh flOw Nasal Cannula Therapy
An observational study of Respiratory Failure and Heart Rate Variability (HRV), run by University Health Network, Toronto at 1 site in Canada.
Trial summary
High-flow nasal cannula is a type of non-invasive respiratory support that helps patients breathe more comfortably. Because the flow is high, it can deliver more oxygen to the lungs and make breathing easier by reducing the effort needed to breathe. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Respiratory Failure, Heart Rate Variability (HRV), High Flow Nasal Cannula
- How many people
- 20 participants
- Where
- 1 siteCanada
- Study dates
- 26 May 2026to Dec 2026
- Phase
- Observational
- 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
Study population: Patients on high flow nasal cannula for respiratory failure at Toronto General Hospital (UHN)
Who may be able to join
- Age > 18
- Currently receiving High-Flow Nasal Cannula Therapy
Who cannot join
- FiO2 ≥ 90%
- Pacemaker rhythm or presence of atrial fibrillation
- Post-cardiac surgery patients
- Contra-indications to electrical impedance tomography (EIT) and/or electrocardiogram (ECG) (active implantable medical device, burns, thoracic wounds limiting electrode placement)
- Non-English-speaking
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Marcela Amaral contact
Canada1 site, 1 recruiting
- Recruiting
Toronto General Hospital
Toronto, Ontario, M5G 2C4
About this study
Official title: Heart Rate Variability as a Marker for Titrating High Flow Nasal Cannula Therapy in Patients With Respiratory Failure
High-flow nasal cannula is a type of non-invasive respiratory support that helps patients breathe more comfortably. Because the flow is high, it can deliver more oxygen to the lungs and make breathing easier by reducing the effort needed to breathe. However, the best strategy to determine the best oxygen flow rate remains uncertain. Reducing flow rates prematurely can increase work of breathing and prolong ICU stay, while unnecessary prolongation can increase costs. Currently, evidence to guide titration is limited.
Heart rate variability is the natural variation in the time between each heartbeat. Heart rate variability reflects the level of autonomic nervous system activity in response to stress. The autonomic nervous system is the part of the nervous system that automatically controls how heart rate speeds up and slows down. When heart rate variability is higher, it indicates that the system is able to adjust to changes in the body, including stress. However, when heart rate variability is low, it indicates that the system is constrained and in a state of stress.
Read more
The VARIATION study is designed to characterize how heart rate variability goal of this observational study is to learn whether heart rate variability can serve as a marker of the appropriateness of high flow nasal cannula flow support during flow titration in patients with respiratory failure. The main question it aims to answer is:
Does heart rate variability change before other conventional respiratory signs when there are changes in respiratory function due to inadequate flow rate?
Participants already on high flow nasal cannula as part of their regular medical care will:
- Undergo a stepwise decrease in high flow nasal cannula flow rate.
- Be recorded continuously with electrocardiogram and electrical impedance tomography.
Read the detailed description
Previous work has established that high flow nasal cannula can improve outcomes in patients with respiratory failure. However, the optimal approach to titrating HFNC therapy remains uncertain. As a consequence, some patients may be under-supported with HFNC, leading to excessive respiratory muscle effort, while others may be needlessly over-supported, unnecessarily prolonging ICU admission. Prolonged use of HFNC increases costs, but premature decreases in HFNC support may contribute to deteriorations in lung function and delayed recovery, ultimately leading to prolonged hospital stays. Conventional metrics such as respiratory rate are relatively insensitive to early changes in respiratory drive and may therefore fail to detect early respiratory stress in response to reduced flow rates.
One possible approach to monitor the adequacy of HFNC support would be to monitor heart rate variability (HRV). HRV reflects autonomic nervous system function, where healthy individuals exhibit higher HRV, indicating freedom within a biological system to adapt to conditions. HRV is also influenced by respiration, where fluctuations in heart rate at respiratory frequency reflects vagal modulation of cardiac activity.
In patients in the intensive care unit, reduced heart rate variability is a sign of more severe illness. Because the heart and lungs work closely together, and are linked through the autonomic nervous system, changes in respiratory function may affect heart rate variability before more conventional signs of respiratory distress become apparent. Despite these findings, HRV monitoring during HFNC titration remains unexplored.
In this prospective, physiologic crossover study participants will undergo stepwise decreases (from 60 L/min to 20 L/min) in high flow nasal cannula flow rate, while being continuously monitored with electrocardiogram (ECG) and electrical impedance tomography (EIT). The FiO2 will be adjusted to maintain a target SpO2 > 90%. Tidal volume, respiratory rate, FiO2, and SpO2 will be collected and ROX and VOX indices will be collected at each flow rate. Heart rate variability measures will be analyzed from ECG recordings.
If HRV is more sensitive to the physiological effects of HFNC titration compared to conventional respiratory metrics, it could serve as a valuable marker for optimizing flow rate and preventing respiratory deterioration. The results of this project will address a gap in current practice and investigate a physiological marker of respiratory stress that could be used to optimize HFNC weaning strategies.
- Keywords
- Electrocardiogram (ECG), Electrical Impedance Tomography (EIT)
- Medical subject headings
- Respiratory Insufficiency
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in heart rate variability during flow titration
Measured: During flow titration, maximum of 1 hour and 45 minutes
Secondary outcomes (2)
Correlation between heart rate variability and respiratory measures during high flow nasal cannula flow titration
Measured: During flow titration, maximum of 1 hour and 45 minutes
Agreement between heart rate variability measures derived from pulse oximetry and those derived from ECG
Measured: During flow titration, maximum of 1 hour and 45 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2026
- Study start26 May 2026
- Primary completionNov 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Respiratory FailureStudies 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
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07518862
- Sponsor's protocol ID
- 25-6168
- Acronym
- VARIATION
- Status last verified
- Jun 2026
- First submitted
- 1 Apr 2026
- Last updated
- 18 Jun 2026
- 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 18 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Heart Rate Variability as a Marker for Titrating High Flow Nasal Cannula Therapy in Patients With Respiratory Failure
- ClinicalTrials.gov ID
- NCT07518862
- Acronym / sponsor ID
- VARIATION / 25-6168
- Keywords
- Electrocardiogram (ECG), Electrical Impedance Tomography (EIT)
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- 26 May 2026 (actual)
- Primary completion
- Nov 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 9 Apr 2026 (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.
High-flow nasal cannula is a type of non-invasive respiratory support that helps patients breathe more comfortably. Because the flow is high, it can deliver more oxygen to the lungs and make breathing easier by reducing the effort needed to breathe. However, the best strategy to determine the best oxygen flow rate remains uncertain. Reducing flow rates prematurely can increase work of breathing and prolong ICU stay, while unnecessary prolongation can increase costs. Currently, evidence to guide titration is limited.
Heart rate variability is the natural variation in the time between each heartbeat. Heart rate variability reflects the level of autonomic nervous system activity in response to stress. The autonomic nervous system is the part of the nervous system that automatically controls how heart rate speeds up and slows down. When heart rate variability is higher, it indicates that the system is able to adjust to changes in the body, including stress. However, when heart rate variability is low, it indicates that the system is constrained and in a state of stress.
The VARIATION study is designed to characterize how heart rate variability goal of this observational study is to learn whether heart rate variability can serve as a marker of the appropriateness of high flow nasal cannula flow support during flow titration in patients with respiratory failure. The main question it aims to answer is:
Does heart rate variability change before other conventional respiratory signs when there are changes in respiratory function due to inadequate flow rate?
Participants already on high flow nasal cannula as part of their regular medical care will:
- Undergo a stepwise decrease in high flow nasal cannula flow rate.
- Be recorded continuously with electrocardiogram and electrical impedance tomography.
Detailed description
Previous work has established that high flow nasal cannula can improve outcomes in patients with respiratory failure. However, the optimal approach to titrating HFNC therapy remains uncertain. As a consequence, some patients may be under-supported with HFNC, leading to excessive respiratory muscle effort, while others may be needlessly over-supported, unnecessarily prolonging ICU admission. Prolonged use of HFNC increases costs, but premature decreases in HFNC support may contribute to deteriorations in lung function and delayed recovery, ultimately leading to prolonged hospital stays. Conventional metrics such as respiratory rate are relatively insensitive to early changes in respiratory drive and may therefore fail to detect early respiratory stress in response to reduced flow rates.
One possible approach to monitor the adequacy of HFNC support would be to monitor heart rate variability (HRV). HRV reflects autonomic nervous system function, where healthy individuals exhibit higher HRV, indicating freedom within a biological system to adapt to conditions. HRV is also influenced by respiration, where fluctuations in heart rate at respiratory frequency reflects vagal modulation of cardiac activity.
In patients in the intensive care unit, reduced heart rate variability is a sign of more severe illness. Because the heart and lungs work closely together, and are linked through the autonomic nervous system, changes in respiratory function may affect heart rate variability before more conventional signs of respiratory distress become apparent. Despite these findings, HRV monitoring during HFNC titration remains unexplored.
In this prospective, physiologic crossover study participants will undergo stepwise decreases (from 60 L/min to 20 L/min) in high flow nasal cannula flow rate, while being continuously monitored with electrocardiogram (ECG) and electrical impedance tomography (EIT). The FiO2 will be adjusted to maintain a target SpO2 > 90%. Tidal volume, respiratory rate, FiO2, and SpO2 will be collected and ROX and VOX indices will be collected at each flow rate. Heart rate variability measures will be analyzed from ECG recordings.
If HRV is more sensitive to the physiological effects of HFNC titration compared to conventional respiratory metrics, it could serve as a valuable marker for optimizing flow rate and preventing respiratory deterioration. The results of this project will address a gap in current practice and investigate a physiological marker of respiratory stress that could be used to optimize HFNC weaning strategies.
Study design
- Observational model
- Other
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients on high flow nasal cannula for respiratory failure at Toronto General Hospital (UHN)
Key inclusion criteria (2 listed)
- Age > 18
- Currently receiving High-Flow Nasal Cannula Therapy
Key exclusion criteria (5 listed)
- FiO2 ≥ 90%
- Pacemaker rhythm or presence of atrial fibrillation
- Post-cardiac surgery patients
- Contra-indications to electrical impedance tomography (EIT) and/or electrocardiogram (ECG) (active implantable medical device, burns, thoracic wounds limiting electrode placement)
- Non-English-speaking
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change in heart rate variability during flow titration
Time frame: During flow titration, maximum of 1 hour and 45 minutes
2 secondary outcomes
Correlation between heart rate variability and respiratory measures during high flow nasal cannula flow titration
Time frame: During flow titration, maximum of 1 hour and 45 minutes
Agreement between heart rate variability measures derived from pulse oximetry and those derived from ECG
Time frame: During flow titration, maximum of 1 hour and 45 minutes
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 18 Jun 2026.
- 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.
Marcela Amaral contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Respiratory Failure and Heart Rate Variability (HRV), 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 2 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: looking for participants now, as of the sponsor's last update on 18 Jun 2026. 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?
Change in heart rate variability during flow titration (time frame: During flow titration, maximum of 1 hour and 45 minutes). 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 18 Jun 2026; AzTrials last refreshed its copy on 26 Oct 2026.