Acute Hypercapnic Respiratory FailureHIFOLD2NCT07157098
Asymmetrical High Flow Oxygen Versus Noninvasive Ventilation in Acute Hypercapnic Respiratory Failure
A study testing asymmetrical high-flow nasal cannula, non-invasive ventilation with standard mask and non-invasive ventilation with a new mask in people with Acute Hypercapnic Respiratory Failure, run by Unity Health Toronto at 1 site in Canada.
Trial summary
NIV is a life-saving treatment for people with breathing failure and carbon dioxide (CO2) retention. It helps remove this waste gas from the lungs and reduces the effort needed to breathe. However, the standard masks used for NIV can become uncomfortable over time, which may lead patients to stop using them. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Hypercapnic Respiratory Failure
- What is being tested?
- asymmetrical high-flow nasal cannula, non-invasive ventilation with standard mask and non-invasive ventilation with a new mask
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteCanada
- Study dates
- 25 Aug 2025to Jul 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosed with acute hypercapnic respiratory failure
- Admitted to the intensive care unit
- Being treated with either high-flow oxygen treatment or non-invasive ventilation
Who cannot join
- Clinical instability - defined as the presence of one of the followings: respiratory rate > 40 breaths/minute, SpO2 < 80%, active broncho-pleural fistula, Glasgow Coma Scale < 8, mean arterial pressure below 60 mmHg despite usage of vasopressors
- Requiring immediate need of endotracheal intubation, according to the judgement of the attending physician
- Contraindications of monitoring with electrical impedance tomography (e.g. pacemaker, chest wall burns wounds limiting electrode placement).
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
St. Michael's Hospital
Toronto, Ontario, M5B1W8
Nattapat Wongtirawit, MD, 4168646060 ext. 6214, nattapat.wongtirawit@unityhealth.to
About this study
NIV is a life-saving treatment for people with breathing failure and carbon dioxide (CO2) retention. It helps remove this waste gas from the lungs and reduces the effort needed to breathe. However, the standard masks used for NIV can become uncomfortable over time, which may lead patients to stop using them. Stopping treatment can be dangerous and may cause breathing problems to worsen. That's why finding devices that are more comfortable and possibly more effective is very important. This study aims to take a first step in that direction.
This is the first study comparing new devices designed to help people with chronic CO2 buildup during breathing flare-ups. Devices tested include a new type of asymmetrical nasal cannula for high-flow oxygen therapy and a new mask called OptiNIV, which has a comfortable design that may help remove more CO2.
These devices will be compared to standard NIV masks currently used in hospitals. Outcome of interests include their effects on the effort needed to breathe, on how much CO2 is cleared, and on how comfortable they are.
- Conditions
- Acute Hypercapnic Respiratory Failure
- Being tested
- asymmetrical high-flow nasal cannula, non-invasive ventilation with standard mask, non-invasive ventilation with a new mask
- Keywords
- acute hypercapnic respiratory failure, non-invasive ventilation, high-flow oxygen
- Medical subject headings
- Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
asymmetrical high-flow nasal cannulaDevice
high-flow nasal oxygen therapy via asymmetrical nasal prongs
non-invasive ventilation with standard maskDevice
non-invasive ventilation with standard oronasal mask, clinically used in the participting site
non-invasive ventilation with a new maskDevice
non-invasive ventilation with a new mask design, with under-nose, bridge-free design
| Study group | Role | What they receive |
|---|---|---|
| All study patient | Experimental | Sequential respiratory support with 3 devices Receives: Device: asymmetrical high-flow nasal cannula; Device: non-invasive ventilation with standard mask; Device: non-invasive ventilation with a new mask |
What is being measured
The primary outcome is the main question the study is designed to answer.
Power of Breathing
A marker of the patient's work of breathing. Calculated by thickening fraction of the diaphragm, multiplied by the respiratory rate.
Measured: Minute 10, 20, and 30
Secondary outcomes (3)
Ventilatory Ratio
A marker of ventilation efficiency. Calculated from carbon dioxide level (in this case, obtained from transcutaneous capnography) and minute ventilation (in this case, obtained from electrical impedance tomography)
Measured: Minute 10, 20, and 30
Patient's comfort
Obtained from a visual analog scale from 1 to 10, with 10 indicating the highest comfort
Measured: Minute 10, 20, and 30
Patient's subjective shortness of breath
Obtained from a visual analog scale from 1 to 10, with 10 indicating the worst shortness of breath
Measured: Minute 10, 20, and 30
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2025
- Study start25 Aug 2025 (estimated)
- Primary completionJun 2026 (estimated)
- Study completionJul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Hypercapnic Respiratory FailureStudies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Sequential
- Model description
- Patients will go through three intervention steps, each with a different breathing support: asymmetrical high-flow nasal cannula (HFNC), non-invasive ventilation (NIV) using the standard NIV mask at the participating center, and NIV using a new mask design. Each step lasts 10 minutes.
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Unity Health Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07157098
- Sponsor's protocol ID
- 25-035
- Acronym
- HIFOLD2
- Status last verified
- Aug 2025
- First submitted
- 15 Aug 2025
- Last updated
- 5 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The datasets generated and/or analyzed during the current study are not publicly available due participant confidentiality, according to the REB, but are available from the corresponding author on reasonable request.
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Asymmetrical High Flow Oxygen Versus Noninvasive Ventilation in Acute Hypercapnic Respiratory Failure
- ClinicalTrials.gov ID
- NCT07157098
- Acronym / sponsor ID
- HIFOLD2 / 25-035
- Conditions
- Acute Hypercapnic Respiratory Failure
- Keywords
- acute hypercapnic respiratory failure, non-invasive ventilation, high-flow oxygen
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Unity Health TorontoUniversity, hospital or other
- Study start
- 25 Aug 2025 (estimated)
- Primary completion
- Jun 2026 (estimated)
- Study completion
- Jul 2026 (estimated)
- First posted
- 5 Sep 2025 (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.
NIV is a life-saving treatment for people with breathing failure and carbon dioxide (CO2) retention. It helps remove this waste gas from the lungs and reduces the effort needed to breathe. However, the standard masks used for NIV can become uncomfortable over time, which may lead patients to stop using them. Stopping treatment can be dangerous and may cause breathing problems to worsen. That's why finding devices that are more comfortable and possibly more effective is very important. This study aims to take a first step in that direction.
This is the first study comparing new devices designed to help people with chronic CO2 buildup during breathing flare-ups. Devices tested include a new type of asymmetrical nasal cannula for high-flow oxygen therapy and a new mask called OptiNIV, which has a comfortable design that may help remove more CO2.
These devices will be compared to standard NIV masks currently used in hospitals. Outcome of interests include their effects on the effort needed to breathe, on how much CO2 is cleared, and on how comfortable they are.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Patients will go through three intervention steps, each with a different breathing support: asymmetrical high-flow nasal cannula (HFNC), non-invasive ventilation (NIV) using the standard NIV mask at the participating center, and NIV using a new mask design. Each step lasts 10 minutes.
| Arm | Type | Receives |
|---|---|---|
| All study patient | Experimental | Device: asymmetrical high-flow nasal cannula, Device: non-invasive ventilation with standard mask, Device: non-invasive ventilation with a new maskSequential respiratory support with 3 devices |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Diagnosed with acute hypercapnic respiratory failure
- Admitted to the intensive care unit
- Being treated with either high-flow oxygen treatment or non-invasive ventilation
Key exclusion criteria (3 listed)
- Clinical instability - defined as the presence of one of the followings: respiratory rate > 40 breaths/minute, SpO2 < 80%, active broncho-pleural fistula, Glasgow Coma Scale < 8, mean arterial pressure below 60 mmHg despite usage of vasopressors
- Requiring immediate need of endotracheal intubation, according to the judgement of the attending physician
- Contraindications of monitoring with electrical impedance tomography (e.g. pacemaker, chest wall burns wounds limiting electrode placement).
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 |
|---|---|---|
| asymmetrical high-flow nasal cannulahigh-flow nasal oxygen therapy via asymmetrical nasal prongs | Device | All study patient |
| non-invasive ventilation with standard masknon-invasive ventilation with standard oronasal mask, clinically used in the participting site | Device | All study patient |
| non-invasive ventilation with a new masknon-invasive ventilation with a new mask design, with under-nose, bridge-free design | Device | All study patient |
Primary outcome
Power of Breathing
Time frame: Minute 10, 20, and 30
A marker of the patient's work of breathing. Calculated by thickening fraction of the diaphragm, multiplied by the respiratory rate.
3 secondary outcomes
Ventilatory Ratio
Time frame: Minute 10, 20, and 30
Patient's comfort
Time frame: Minute 10, 20, and 30
Patient's subjective shortness of breath
Time frame: Minute 10, 20, and 30
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 5 Sep 2025.
- Individual participant dataSharing planned: No. The datasets generated and/or analyzed during the current study are not publicly available due participant confidentiality, according to the REB, but are available from the corresponding author on reasonable request.
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Management of Post-operative Respiratory Failure by Using NIV and High Velocity Nasal Insufflation (HVNI)
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Extracorporeal Carbon Dioxide Removal Plus Noninvasive Ventilation in Patients With COPD Not Eligible for Intubation
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing asymmetrical high-flow nasal cannula, non-invasive ventilation with standard mask and non-invasive ventilation with a new mask in people with Acute Hypercapnic Respiratory Failure, 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 3 inclusion and 3 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: opening soon, as of the sponsor's last update on 5 Sep 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?
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 Nattapat Wongtirawit, M.D. (416-864-6060 ext. 6214, nattapat.wongtirawit@unityhealth.to), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Power of Breathing (time frame: Minute 10, 20, and 30). 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 5 Sep 2025.