Exacerbation CopdHiFOLDNCT03033251
High Flow Nasal Cannula Versus Non-Invasive Ventilation in Exacerbations of Chronic Obstructive Pulmonary Disease
A study testing Non Invasive Ventilation, High Flow Oxygen Cannula 50 and High Flow Oxygen Cannula 30 in people with Exacerbation Copd and Acute Respiratory Distress, run by Unity Health Toronto at 1 site in Canada.
Trial summary
Chronic obstructive lung disease is a disabling disease that affects people usually after several years of smoke tobacco exposure and affects millions of patients worldwide. The disease is marked by multiples episode of worsening, termed exacerbations necessitating frequent hospitalizations. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Exacerbation Copd, Acute Respiratory Distress, Acute Hypercapnic Respiratory Failure
- What is being tested?
- Non Invasive Ventilation, High Flow Oxygen Cannula 50 and High Flow Oxygen Cannula 30
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteCanada
- Study dates
- 2 Sep 2018to 1 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 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- COPD exacerbation and acute hypercapnic respiratory failure with acute respiratory failure defined by
- Respiratory acidosis (pH ≤7.35 and PaCO2 ≥45 mmHg);
- Respiratory rate≥20 breaths/min;
- Activation of accessory respiratory muscles;
- Undergone at NIV or HFNC since their admission
- English speaking
- Adult patient with age > 40 year old.
Who cannot join
- Severe respiratory acidosis defined by pH<7.25
- Decreased level of consciousness (Glasgow Coma Score Scale < 11)
- Urgent intubation required
- Pneumothorax with pleural drainage and persistent air leak
- Hemodynamic instability requiring vasopressors
- Uncooperative
Show all 9Show fewer
- Patients with skin or chest wall or abdominal trauma (potentially worsened by placement of a surface sensor)
- Clinical judgement of the attending physician
- Body mass index > 40 kg/m2
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
St. Michael's Hospital
Toronto, Ontario, M5B 1W8
Laurent Brochard, brochardl@smh.ca
About this study
Official title: High Flow Nasal Cannula Versus Non-Invasive Ventilation in Exacerbations of Chronic Obstructive Pulmonary Disease and Hypercapnic Respiratory Failure
Chronic obstructive lung disease is a disabling disease that affects people usually after several years of smoke tobacco exposure and affects millions of patients worldwide. The disease is marked by multiples episode of worsening, termed exacerbations necessitating frequent hospitalizations. During these exacerbations, patients present breathless, and in the most severe cases, are admitted to an Intensive Care Unit (ICU) for respiratory assistance. Currently, respiratory assistance is provided by a ventilator via a oronasal mask (referred to non-invasive ventilation, NIV), that helps patients to cope with their breathless. The mask is not always well tolerated and the ventilator sessions are delivered intermittently. In the past decade, a new technique that provides air-oxygen with high flow has been developed. This technique, called High Flow via Nasal Cannula (HFNC) can deliver from 21 to 100% heated and humidified air-oxygen at a high flow of gas via simple nasal cannula. Recent studies have shown that the technique is very efficient to treat patients presenting with acute respiratory failure who don't have any underlying chronic pulmonary disease. Whether the technique would be also efficient in patients with COLD presenting with severe exacerbations has not yet been demonstrated. Since HFNC does not require any mask, it is thought that the comfort of the patient would be much better in comparison to NIV and could potentially help to treat many patients with the disease. The objective of the present study is to study the physiological effect of HFNC as compared to NIV in patients with severe exacerbations of COPD and to show that it is non-inferior to NIV.
Read the detailed description
Design: Prospective, observational, cross-over, clinical physiologic study of HFNC and NIV in patients with COPD and hypercapnic respiratory failure Intervention: Participants will be consecutively ventilated with the two devices, i.e., HFNC and NIV. HFNC 30 and 50 L/min will be applied in a random order (sealed, opaque envelope). HFNC will be set with a temperature at 37°C or 34°C if perceived as too warm. NIV settings will be adjusted based on the clinical assessment of the Respiratory Therapist as per standard practice and will not be modified during the test. In both groups, FiO2 will be adjusted to achieve a SpO2 of at least 92%.
Setting: The intervention will be applied in the Medical-Surgical ICU of St. Michael's Hospital.
Duration: Each device will be studied for up to 30 minutes. The entire study will take place over up to 3 hours. There is no additional follow-up thereafter.
Procedures: The study will start first by recording patients under spontaneous breathing considered as a baseline (sequence #1). Under spontaneous breathing, patients will be receiving oxygen therapy as it is usually done between 2 NIV sessions. Then, the patient will have up to 30 minutes to acclimatize to HFNC and select his/her preferred flow rate (sequence #2). NIV will be applied (sequence #3). The NIV settings will be adjusted based on the clinical assessment of the Respiratory Therapist and will not be modified throughout the study. Then, according to randomization order (sealed envelopes), patients will receive a flow corresponding to the preferred flow selected by the patient and a second flow, either HFNC 30 L/min or HFNC 50 L/min depending on the initial choice (sequences #4 and #5) (see flow diagram). FiO2 will be adjusted to achieve a SpO2 of 90 to 94%. Each condition will be studied fup to 30 minutes and will be separated by a 5-minute washout period during which patients will be receiving oxygen therapy. The measurements will be collected at baseline (under spontaneous breathing) and during the last five minutes of each condition. In case of clinical intolerance as considered by the attending physician, the study will stop. In case the patient is considered dependent of NIV by clinicians, we will still enroll the patient without doing baseline period after discussion with clinicians.
The pulse oximeter (SpO2) and transcutaneous CO2 monitor (SenTec Digital Monitoring System (SDMS)) will be continuously monitored throughout the study period. Exspiron or Electrical Impedance Tomography (EIT) device will be calibrated to measure minute ventilation. Four surface electrodes will be placed bilaterally to record each hemidiaphragm activity using a specific recording system (Acqknowledge software, Biopac Systems) A bedside ultrasound examination will be performed, using a SonoSite system (Fujifilm) equipped with a 10-15 MHz ultrasound linear probe. Diaphragm thickness will be measured both at end-inspiration and end-expiration. This technique will be applied at the end of each sequence (before ventilatory assist under conventional O2 therapy). In patients becoming rapidly intolerant to NIV disconnection, we will limit this "baseline" period under O2 to a minimum (5 minutes). The thickness and contraction of the intercostal muscles and abdominal muscles will also be assessed.
Interpretation of the ultrasound results to determine diaphragm and other muscle thickness will be read at a later time by an individual blinded to the intervention.
- Being tested
- Non Invasive Ventilation, High Flow Oxygen Cannula 50, High Flow Oxygen Cannula 30
- Keywords
- COPD exacerbation, Work of breathing, Non invasive ventilation, High Flow Oxygen Cannula, Acute Hypercapnic Respiratory Failure
- Medical subject headings
- Acute Lung Injury, Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Non Invasive VentilationDevice
Also called Standard of Care
Patients will receive non invasive ventilation as a standard of care.
High Flow Oxygen Cannula 50Device
Also called HFNO 50
Patients will receive High Flow Oxygen Cannula with a flow set at 50 L/min
High Flow Oxygen Cannula 30Device
Also called HFNO 30
Patients will receive High Flow Oxygen Cannula with a flow set at 30 L/min
| Study group | Role | What they receive |
|---|---|---|
| Non invasive ventilation | Active comparator | Patients will receive non invasive ventilation with setting decided by the attending physician. Receives: Device: Non Invasive Ventilation |
| High Flow 50 L/min | Active comparator | High Flow Oxygen Cannula with a flow set at 50 L/min. Receives: Device: High Flow Oxygen Cannula 50 |
| High Flow 30 L/min | Active comparator | High Flow Oxygen Cannula with a flow set at 30 L/min. Receives: Device: High Flow Oxygen Cannula 30 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in work of breathing between NIV and HFNC
The primary endpoint is to compare the decrease in work of breathing under HFNC to the decrease in work of breathing under NIV.
The work of breathing will be assessed with diaphragm ultrasound (measurement of the diaphragm thickening fraction).
Measured: 30 minutes
Secondary outcomes (1)
Change in Work of breathing between HFNC 50 and 30 L/min
The secondary endpoints include comparison of the work of breathing under HFNC (50L/min vs 30 L/min).
The work of breathing will be assessed with diaphragm ultrasound (measurement of the diaphragm thickening fraction).
Measured: 30 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2017 (estimated)
- Study start2 Sep 2018
- Primary completion11 Apr 2025
- Study completion1 Jul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Exacerbation CopdStudies 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
- Randomised
- Intervention model
- Crossover
- Model description
- Participants will receive 2 treatments (non invasive ventilation and high flow nasal cannula). The high flow nasal cannula will be applied with 2 flows (50 L/min and 30 L/min). The order of application of the 2 high flow sequences will be randomized (sealed opaque enveloppes).
- 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
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03033251
- Sponsor's protocol ID
- REB# 16-389
- Acronym
- HiFOLD
- Status last verified
- May 2025
- First submitted
- 19 Jan 2017
- 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
- High Flow Nasal Cannula Versus Non-Invasive Ventilation in Exacerbations of Chronic Obstructive Pulmonary Disease and Hypercapnic Respiratory Failure
- ClinicalTrials.gov ID
- NCT03033251
- Acronym / sponsor ID
- HiFOLD / REB# 16-389
- Keywords
- COPD exacerbation, Work of breathing, Non invasive ventilation, High Flow Oxygen Cannula, Acute Hypercapnic Respiratory Failure
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Unity Health TorontoUniversity, hospital or other
- Study start
- 2 Sep 2018 (actual)
- Primary completion
- 11 Apr 2025 (actual)
- Study completion
- 1 Jul 2026 (estimated)
- First posted
- 26 Jan 2017 (estimated)
- 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.
Chronic obstructive lung disease is a disabling disease that affects people usually after several years of smoke tobacco exposure and affects millions of patients worldwide. The disease is marked by multiples episode of worsening, termed exacerbations necessitating frequent hospitalizations. During these exacerbations, patients present breathless, and in the most severe cases, are admitted to an Intensive Care Unit (ICU) for respiratory assistance. Currently, respiratory assistance is provided by a ventilator via a oronasal mask (referred to non-invasive ventilation, NIV), that helps patients to cope with their breathless. The mask is not always well tolerated and the ventilator sessions are delivered intermittently. In the past decade, a new technique that provides air-oxygen with high flow has been developed. This technique, called High Flow via Nasal Cannula (HFNC) can deliver from 21 to 100% heated and humidified air-oxygen at a high flow of gas via simple nasal cannula. Recent studies have shown that the technique is very efficient to treat patients presenting with acute respiratory failure who don't have any underlying chronic pulmonary disease. Whether the technique would be also efficient in patients with COLD presenting with severe exacerbations has not yet been demonstrated. Since HFNC does not require any mask, it is thought that the comfort of the patient would be much better in comparison to NIV and could potentially help to treat many patients with the disease. The objective of the present study is to study the physiological effect of HFNC as compared to NIV in patients with severe exacerbations of COPD and to show that it is non-inferior to NIV.
Detailed description
Design: Prospective, observational, cross-over, clinical physiologic study of HFNC and NIV in patients with COPD and hypercapnic respiratory failure Intervention: Participants will be consecutively ventilated with the two devices, i.e., HFNC and NIV. HFNC 30 and 50 L/min will be applied in a random order (sealed, opaque envelope). HFNC will be set with a temperature at 37°C or 34°C if perceived as too warm. NIV settings will be adjusted based on the clinical assessment of the Respiratory Therapist as per standard practice and will not be modified during the test. In both groups, FiO2 will be adjusted to achieve a SpO2 of at least 92%.
Setting: The intervention will be applied in the Medical-Surgical ICU of St. Michael's Hospital.
Duration: Each device will be studied for up to 30 minutes. The entire study will take place over up to 3 hours. There is no additional follow-up thereafter.
Procedures: The study will start first by recording patients under spontaneous breathing considered as a baseline (sequence #1). Under spontaneous breathing, patients will be receiving oxygen therapy as it is usually done between 2 NIV sessions. Then, the patient will have up to 30 minutes to acclimatize to HFNC and select his/her preferred flow rate (sequence #2). NIV will be applied (sequence #3). The NIV settings will be adjusted based on the clinical assessment of the Respiratory Therapist and will not be modified throughout the study. Then, according to randomization order (sealed envelopes), patients will receive a flow corresponding to the preferred flow selected by the patient and a second flow, either HFNC 30 L/min or HFNC 50 L/min depending on the initial choice (sequences #4 and #5) (see flow diagram). FiO2 will be adjusted to achieve a SpO2 of 90 to 94%. Each condition will be studied fup to 30 minutes and will be separated by a 5-minute washout period during which patients will be receiving oxygen therapy. The measurements will be collected at baseline (under spontaneous breathing) and during the last five minutes of each condition. In case of clinical intolerance as considered by the attending physician, the study will stop. In case the patient is considered dependent of NIV by clinicians, we will still enroll the patient without doing baseline period after discussion with clinicians.
The pulse oximeter (SpO2) and transcutaneous CO2 monitor (SenTec Digital Monitoring System (SDMS)) will be continuously monitored throughout the study period. Exspiron or Electrical Impedance Tomography (EIT) device will be calibrated to measure minute ventilation. Four surface electrodes will be placed bilaterally to record each hemidiaphragm activity using a specific recording system (Acqknowledge software, Biopac Systems) A bedside ultrasound examination will be performed, using a SonoSite system (Fujifilm) equipped with a 10-15 MHz ultrasound linear probe. Diaphragm thickness will be measured both at end-inspiration and end-expiration. This technique will be applied at the end of each sequence (before ventilatory assist under conventional O2 therapy). In patients becoming rapidly intolerant to NIV disconnection, we will limit this "baseline" period under O2 to a minimum (5 minutes). The thickness and contraction of the intercostal muscles and abdominal muscles will also be assessed.
Interpretation of the ultrasound results to determine diaphragm and other muscle thickness will be read at a later time by an individual blinded to the intervention.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Participants will receive 2 treatments (non invasive ventilation and high flow nasal cannula). The high flow nasal cannula will be applied with 2 flows (50 L/min and 30 L/min). The order of application of the 2 high flow sequences will be randomized (sealed opaque enveloppes).
| Arm | Type | Receives |
|---|---|---|
| Non invasive ventilation | Active comparator | Device: Non Invasive VentilationPatients will receive non invasive ventilation with setting decided by the attending physician. |
| High Flow 50 L/min | Active comparator | Device: High Flow Oxygen Cannula 50High Flow Oxygen Cannula with a flow set at 50 L/min. |
| High Flow 30 L/min | Active comparator | Device: High Flow Oxygen Cannula 30High Flow Oxygen Cannula with a flow set at 30 L/min. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- COPD exacerbation and acute hypercapnic respiratory failure with acute respiratory failure defined by
- Undergone at NIV or HFNC since their admission
- English speaking
- Adult patient with age > 40 year old.
Key exclusion criteria (9 listed)
- Severe respiratory acidosis defined by pH<7.25
- Decreased level of consciousness (Glasgow Coma Score Scale < 11)
- Urgent intubation required
- Pneumothorax with pleural drainage and persistent air leak
- Hemodynamic instability requiring vasopressors
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 |
|---|---|---|
| Non Invasive VentilationAlso: Standard of CarePatients will receive non invasive ventilation as a standard of care. | Device | Non invasive ventilation |
| High Flow Oxygen Cannula 50Also: HFNO 50Patients will receive High Flow Oxygen Cannula with a flow set at 50 L/min | Device | High Flow 50 L/min |
| High Flow Oxygen Cannula 30Also: HFNO 30Patients will receive High Flow Oxygen Cannula with a flow set at 30 L/min | Device | High Flow 30 L/min |
Primary outcome
Change in work of breathing between NIV and HFNC
Time frame: 30 minutes
The primary endpoint is to compare the decrease in work of breathing under HFNC to the decrease in work of breathing under NIV. The work of breathing will be assessed with diaphragm ultrasound (measurement of the diaphragm thickening fraction).
1 secondary outcome
Change in Work of breathing between HFNC 50 and 30 L/min
Time frame: 30 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 20 May 2025.
- Individual participant dataSharing planned: No
Related trials for Exacerbation Copd
RecruitingPhase 2
Rademikibart IV for Acute Asthma and COPD Exacerbation
Asthma Acute, COPD Exacerbation Acute
Recruiting
A Prospective Study of Cardiovascular Risk of Patients Admitted for Acute Exacerbation of COPD
COPD
Active, not recruitingObservational study
CareCOPD - COPD Home Monitoring Study
Chronic Obstructive Pulmonary Disease
Not yet recruitingPhase 4
Efficacy of Nebulized Long-Acting Bronchodilators (Formoterol and Revefenacin) vs. Short-Acting Bronchodilators (Albuterol and Ipratropium) in Patients Presenting to the Emergency Department With Acute Exacerbation of COPD (ECOPD)
COPD Exacerbation
RecruitingPhase 4
This After Market Study is Seeing if Dupilumab Plus Usual Standard of Care (SOC) is Better Than Usual Care Alone for Adult Participants After a Severe Chronic Obstructive Pulmonary Disease (COPD) Flare-Up Requiring Hospitalization
Chronic Obstructive Pulmonary Disease (COPD)
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 Non Invasive Ventilation, High Flow Oxygen Cannula 50 and High Flow Oxygen Cannula 30 in people with Exacerbation Copd and Acute Respiratory Distress, 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 7 inclusion and 9 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 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?
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 Laurent Brochard, MD (+1 416 864 5686, BrochardL@smh.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in work of breathing between NIV and HFNC (time frame: 30 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 20 May 2025.