De Novo Hypoxemic Acute Respiratory Failure (hARF)HighCPAPNCT06213168
Impact on Mortality of a Strategy Including Continuous Positive Airway Pressure Plus High Flow Nasal Cannula Oxygen Therapy Versus High Flow Nasal Cannula Oxygen Therapy Alone in Patients With de Novo Acute Hypoxemic Respiratory Failure: a Prospective, Randomized Controlled Trial.
A study testing HFNC and CPAP and HFNC in people with De Novo Hypoxemic Acute Respiratory Failure (hARF), run by Assistance Publique - Hôpitaux de Paris at 29 sites in France.
Trial summary
De novo hypoxemic acute respiratory failure (hARF) is one of the main causes of intensive care unit (ICU) admission. In de novo hARF, intubation is associated with a dramatic increase in mortality rate. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- De Novo Hypoxemic Acute Respiratory Failure (hARF)
- What is being tested?
- HFNC and CPAP and HFNC
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,084 participants
- Where
- 29 sitesFrance
- Study dates
- 19 Aug 2025to Mar 2027
- 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
- Adults (≥ 18 years old)
- Admitted in the ICU for ≤ 24 hours
- De novo hARF defined by the three following criteria:
- Respiratory rate > 25 breaths/min or signs of respiratory distress such as labored breathing or paradoxical inspiration
- PaO2/FiO2 ≤ 200 mmHg under HFNC with flow ≥ 45 L/min, actual FiO2 being considered.
- Uni or bilateral pulmonary infiltrate on chest X-ray or CT scan
- Informed consent from the patient or her/his next of kin or another substitute decision maker, or inclusion procedure in emergency if the patient is unable to consent
Who cannot join
- Refusal of study participation by the patient or the proxy
- Anatomical factors precluding the use of a nasal cannula or CPAP
- Long term oxygen
- Home CPAP or NIV or CPAP or NIV initiated prior to ICU admission
- Hypercapnia indicating NIV (PaCO2 > 45 mmHg)
- Isolated cardiogenic pulmonary oedema indicating NIV
Show all 16Show fewer
- Known pregnancy or breastfeeding
- Absence of coverage by the French statutory health care insurance system (including AME)
- Abdominal, thoracic or cardiac surgery within the last 6 days
- Use of vasopressors (norepinephrine>0.3 mcg/kg/min)
- Glasgow coma scale < 13
- Urgent need for endotracheal intubation
- Patients at an end-of-life stage receiving compational oxygenation
- Exacerbation of a chronic respiratory disease
- Legal protection (curatorship or tutorship)
- Undrained pneumothorax
Trial locations and contacts
29 sites in 1 country. Contact the study team or a site near you to ask about taking part.
29 sites in 1 country
France29 sites, 28 recruiting
- Not yet recruiting
CHU Amiens-Picardie
Amiens, 80054
Clément BRAULT, MD, +33322087809, brault.clément@chu-amiens.fr
- Not yet recruiting
CHU Angers
Angers, 49933
Alain MERCAT, MD, +33241353815, alain.mercat@univ-angers.fr
- Not yet recruiting
Centre Hospitalier Victor Dupouy
Argenteuil, 95107
Gaëtan PLANTEFEVE, MD, +33134232791, gaetan.plantefeve@ch-argenteuil.fr
- Not yet recruiting
Hôpital Avicenne
Bobigny, 93000
Nathan EBSTEIN, MD, +33148026680, Nathan.ebstein@aphp.fr
- Recruiting
Centre Hospitalier de Bourg-en-Bresse - Site de Fleyriat
Bourg-en-Bresse, 01012
Nicholas SEDILLOT, MD, +33474454184, nsedillot@ch-bourg01.fr
- Not yet recruiting
Hôpital Louis-Mourier
Colombes, 92700
Jeoffrey PIRAULT, MD, +33147605066, jeoffrey.pirault@aphp.fr
- Not yet recruiting
Centre Hospitalier Sud Francilien
Corbeil-Essonnes, 91100
Nicolas BEARD, MD, +33161695222, Nicolas.beard@chsf.fr
- Recruiting
Hôpital Henri-Mondor
Créteil, 94010
Guillaume CARTEAUX, MD, +33149812389, guillaume.carteaux@aphp.fr
- Recruiting
Centre Hospitalier de Dieppe - Site Pasteur
Dieppe, 76200
Jean-Philippe RIGAUD, MD, +33232147101, JRigaud@ch-dieppe.fr
- Recruiting
Hôpital François Mitterrand
Dijon, 21000
Jean-Pierre QUENOT, MD, +33380293685, jean-pierre.quenot@chu-dijon.fr
- Recruiting
Hôpital André Mignot
Le Chesnay, 78157
Alexis FERRÉ, MD, +33139638700, ferrealexis@gmail.com
- Not yet recruiting
Hôpital Bicêtre
Le Kremlin-Bicêtre, 94270
Tai Olivier PHAM, MD, +33145217245, Tai.pham@aphp.fr
- Recruiting
Centre Hospitalier du Mans
Le Mans, 72037
Cédric DARREAU, MD, +33243432458, cdarreau@ch-lemans.fr
- Recruiting
Hôpital Salengro
Lille, 59037
Côme BUREAU, MD, +33320444084, come.bureau@chru-lille.fr
- Recruiting
Hôpital Édouard Herriot - Hospices Civils de Lyon
Lyon, 69003
Laurent ARGAUD, MD, +33472112862, laurent.argaud@chu-lyon.fr
- Recruiting
Hôpital de la Croix-Rousse - Hospices Civils de Lyon
Lyon, 69004
Jean-Christophe RICHARD, MD, +33426109272, j-christophe.richard@chu-lyon.fr
- Not yet recruiting
Hôpital Saint-Joseph Saint-Luc
Lyon, 69007
Emmanuel VIVIER, MD, +33478618223, evivier@saintjosephsaintluc.fr
- Not yet recruiting
Hôpital Lyon Sud - Hospices Civils de Lyon
Lyon, 69495
Auguste DARGENT, MD, +33472117311, auguste.dargent@chu-lyon.fr
- Recruiting
Hôpital Lapeyronie
Montpellier, 34090
Kada KLOUCHE, MD, +33467338441, k-klouche@chu-montpellier.fr
- Not yet recruiting
CHU de Nantes
Nantes, 44000
Marie GAUVRIT, MD, +33240087369, Marie.gauvrit@chu-nantes.fr
- Active, not recruiting
Hôpital Pasteur
Nice, 06000
- Recruiting
Hôpital de l'Archet
Nice, 06200
Clément SACCHERI, MD, +33492035510, saccheri.c@chu-nice.fr
- Recruiting
Hôpital Saint-Antoine
Paris, 75012
Eric MAURY, MD, +33149282318, Eric.maury@aphp.fr
- Recruiting
APHP - hôpital Pitié-Salpêtrière
Paris, 75013
Alexandre DEMOULE, MD, +33142167761, alexandre.demoule@aphp.fr
- Recruiting
Hôpital Tenon
Paris, 75020
Alexandra BEURTON, MD, +33156016572, alexandra.beurton@aphp.fr
- Not yet recruiting
Hôpital la Milétrie
Poitiers, 86000
Arnaud THILLE, MD, +33549444367, arnaud.thille@chu-poitiers.fr
- Not yet recruiting
Hôpital Pontchaillou
Rennes, 35000
Nicolas TERZI, MD, +33476767109, Nicolas.terzi@chu-rennes.fr
- Recruiting
Hôpital Charles-Nicolle
Rouen, 76000
Christophe GIRAULT, MD, +33232888261, christophe.girault@chu-rouen.fr
- Recruiting
Nouvel hôpital civil
Strasbourg, 67000
Hamid MERDJI, MD, +33369551211, Hamid.merdji@chru-strasbourg.fr
About this study
Official title: Impact on Mortality of a Strategy Including Continuous Positive Airway Pressure Plus High Flow Nasal Cannula Oxygen Therapy Versus High Flow Nasal Cannula Oxygen Therapy Alone in Patients With de Novo Acute Hypoxemic Respiratory Failure: a Prospective, Randomized Controlled Trial
De novo hypoxemic acute respiratory failure (hARF) is one of the main causes of intensive care unit (ICU) admission. In de novo hARF, intubation is associated with a dramatic increase in mortality rate. Compared to standard oxygen, the use of high-flow oxygen nasal cannula (HFNC) might be beneficial to prevent intubation and mortality, although the results of trials and meta-analyses are conflicting. Even with HFNC, the intubation rate remains high. This is the reason why adjunctive therapies, administered in addition to HFNC are needed.
Continuous positive airway pressure (CPAP) is one of these adjunctive therapies. CPAP provides high level of positive end-expiratory pressure that ensures lung recruitment, but without adding inspiratory pressure support, which prevents ventilator induced lung injury. In addition, as opposed to pressure support, CPAP is well tolerated during long periods of time. Therefore, applying CPAP in addition to HFNC may reduce intubation rate and in turn mortality rate.
The present trial will evaluate the impact on mortality of a strategy including continuous positive airway pressure plus high flow nasal cannula oxygen therapy versus high flow nasal cannula oxygen therapy alone in patients with de novo acute hypoxemic respiratory failure: a Prospective, Randomized Controlled Trial
- Being tested
- HFNC, CPAP and HFNC
- Keywords
- Continuous positive airway pressure, High flow nasal cannula oxygen therapy, De novo hypoxemic acute respiratory failure, Intensive care unit, Mortality, Mechanical ventilation, Non-invasive ventilation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HFNCOther
Also called High flow nasal cannula oxygen therapy
Patients assigned to the control group will be continuously treated by HFNC. HFNC will be initiated within one hour following randomization
CPAP and HFNCOther
Also called Continuous positive airway pressure and High flow nasal canulae
Patients assigned to the intervention group will receive high flow nasal oxygen plus CPAP sessions
| Study group | Role | What they receive |
|---|---|---|
| HFNC | Experimental | Patients assigned to the control group will be continuously treated by HFNC. HFNC will be initiated within one hour following randomization. Receives: Other: HFNC |
| HFNC with CPAP | Experimental | Patients assigned to the intervention group will receive high flow nasal oxygen plus CPAP sessions Receives: Other: HFNC; Other: CPAP and HFNC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mortality
Time to death within the 90 days after randomization
Measured: 90 days
Secondary outcomes (16)
Time from randomization to intubation.
Measured: 28 days
Intensity of dyspnea until intubation as assessed by a visual analogic scale from zero (no dyspnea) to 100 (maximum possible dyspnea).
Measured: 2, 6, 12 and 24 hours
Respiratory rate
Measured: 6, 12 and 24 hours
ROX index
Measured: 6, 12 and 24 hours
Evaluation of intolerance to oxygenation technique until intubation
evaluation based on the following physical criteria: eyes dryness, nose dryness and/or feeling of gastric distention
Measured: 12 and 24 hours
Discomfort associated with the interface as assessed by a visual analogic scale from zero (no discomfort) to 100 (maximum possible discomfort).
Measured: 12 and 24 hours
Level of oxygenation assessed by blood gas that will be sampled on the request of the physician in charge (clinical purpose only).
Measured: First 24 hours or until intubation
Use of NIV for one of the following predefined indication criteria.
- the constitution of a clear indication such as acute-on-chronic respiratory failure with respiratory acidosis (pH < 7.35) or acute cardiogenic pulmonary edema,
- pre oxygenation before intubation,
- fiberoptic bronchoscopy.
Measured: through study completion
Death within the ICU
Measured: through patient participation period,180 days maximum
Time to death
Measured: through patient participation period, an average of 180 days maximum
Death within the hospital and time to death.
Measured: through patient participation period,180 days maximum
Number of invasive ventilation-free days at 28 days defined as days alive and without intubation.
One point will be given for each day during the measurement period, i.e. from the first day of randomization to day 28 that patients will be both alive and free of invasive mechanical ventilation. Zero value will be given for patients who die before day 28.
Measured: Between day 1 and day 28
Number of HFNC-free days at 28 days defined as days non-intubated, alive and without HFNC.
One point will be given for each day during the measurement period, i.e. from the first day of randomization to day 28 that patients will be both alive and free of HFNO and invasive mechanical ventilation. Zero value will be given for patients who die or are intubated before day 28.
Measured: Between day 1 and day 28.
ICU length of stay.
Measured: through patient participation period,180 days maximum
Hospital length of stay.
Measured: through patient participation period,180 days maximum
Occurrence of any adverse event during the ICU stay, with a particular focus on hospital or ventilator associated pneumonia, non-respiratory infections, cardiac arrhythmia, and cardiac arrest.
Measured: through patient participation period,180 days maximum
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2024
- Study start19 Aug 2025
- Primary completionDec 2026 (estimated)
- Study completionMar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for De Novo Hypoxemic Acute Respiratory Failure (hARF)Studies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a prospective multicentre open-label randomized controlled superiority trial with two parallel arms comparing two oxygenation strategies, HFNC plus CPAP versus HFNC alone, in patients admitted in ICU for de novo hARF.
- Masking
- None (open label)
- Enrolment
- 1,084 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06213168
- Sponsor's protocol ID
- APHP220813
- Acronym
- HighCPAP
- Status last verified
- Apr 2026
- First submitted
- 18 Dec 2023
- Last updated
- 13 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data are available upon reasonable request The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients. Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact on Mortality of a Strategy Including Continuous Positive Airway Pressure Plus High Flow Nasal Cannula Oxygen Therapy Versus High Flow Nasal Cannula Oxygen Therapy Alone in Patients With de Novo Acute Hypoxemic Respiratory Failure: a Prospective, Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT06213168
- Acronym / sponsor ID
- HighCPAP / APHP220813
- Keywords
- Continuous positive airway pressure, High flow nasal cannula oxygen therapy, De novo hypoxemic acute respiratory failure, Intensive care unit, Mortality, Mechanical ventilation, Non-invasive ventilation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 1,084 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 19 Aug 2025 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Mar 2027 (estimated)
- First posted
- 19 Jan 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.
De novo hypoxemic acute respiratory failure (hARF) is one of the main causes of intensive care unit (ICU) admission. In de novo hARF, intubation is associated with a dramatic increase in mortality rate. Compared to standard oxygen, the use of high-flow oxygen nasal cannula (HFNC) might be beneficial to prevent intubation and mortality, although the results of trials and meta-analyses are conflicting. Even with HFNC, the intubation rate remains high. This is the reason why adjunctive therapies, administered in addition to HFNC are needed.
Continuous positive airway pressure (CPAP) is one of these adjunctive therapies. CPAP provides high level of positive end-expiratory pressure that ensures lung recruitment, but without adding inspiratory pressure support, which prevents ventilator induced lung injury. In addition, as opposed to pressure support, CPAP is well tolerated during long periods of time. Therefore, applying CPAP in addition to HFNC may reduce intubation rate and in turn mortality rate.
The present trial will evaluate the impact on mortality of a strategy including continuous positive airway pressure plus high flow nasal cannula oxygen therapy versus high flow nasal cannula oxygen therapy alone in patients with de novo acute hypoxemic respiratory failure: a Prospective, Randomized Controlled Trial
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This is a prospective multicentre open-label randomized controlled superiority trial with two parallel arms comparing two oxygenation strategies, HFNC plus CPAP versus HFNC alone, in patients admitted in ICU for de novo hARF.
| Arm | Type | Receives |
|---|---|---|
| HFNC | Experimental | Other: HFNCPatients assigned to the control group will be continuously treated by HFNC. HFNC will be initiated within one hour following randomization. |
| HFNC with CPAP | Experimental | Other: HFNC, Other: CPAP and HFNCPatients assigned to the intervention group will receive high flow nasal oxygen plus CPAP sessions |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Adults (≥ 18 years old)
- Admitted in the ICU for ≤ 24 hours
- De novo hARF defined by the three following criteria:
- Informed consent from the patient or her/his next of kin or another substitute decision maker, or inclusion procedure in emergency if the patient is unable to consent
Key exclusion criteria (16 listed)
- Refusal of study participation by the patient or the proxy
- Anatomical factors precluding the use of a nasal cannula or CPAP
- Long term oxygen
- Home CPAP or NIV or CPAP or NIV initiated prior to ICU admission
- Hypercapnia indicating NIV (PaCO2 > 45 mmHg)
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 |
|---|---|---|
| HFNCAlso: High flow nasal cannula oxygen therapyPatients assigned to the control group will be continuously treated by HFNC. HFNC will be initiated within one hour following randomization | Other | HFNC, HFNC with CPAP |
| CPAP and HFNCAlso: Continuous positive airway pressure and High flow nasal canulaePatients assigned to the intervention group will receive high flow nasal oxygen plus CPAP sessions | Other | HFNC with CPAP |
Primary outcome
Mortality
Time frame: 90 days
Time to death within the 90 days after randomization
16 secondary outcomes
Time from randomization to intubation.
Time frame: 28 days
Intensity of dyspnea until intubation as assessed by a visual analogic scale from zero (no dyspnea) to 100 (maximum possible dyspnea).
Time frame: 2, 6, 12 and 24 hours
Respiratory rate
Time frame: 6, 12 and 24 hours
ROX index
Time frame: 6, 12 and 24 hours
Evaluation of intolerance to oxygenation technique until intubation
Time frame: 12 and 24 hours
Discomfort associated with the interface as assessed by a visual analogic scale from zero (no discomfort) to 100 (maximum possible discomfort).
Time frame: 12 and 24 hours
Level of oxygenation assessed by blood gas that will be sampled on the request of the physician in charge (clinical purpose only).
Time frame: First 24 hours or until intubation
Use of NIV for one of the following predefined indication criteria.
Time frame: through study completion
Death within the ICU
Time frame: through patient participation period,180 days maximum
Time to death
Time frame: through patient participation period, an average of 180 days maximum
Death within the hospital and time to death.
Time frame: through patient participation period,180 days maximum
Number of invasive ventilation-free days at 28 days defined as days alive and without intubation.
Time frame: Between day 1 and day 28
Number of HFNC-free days at 28 days defined as days non-intubated, alive and without HFNC.
Time frame: Between day 1 and day 28.
ICU length of stay.
Time frame: through patient participation period,180 days maximum
Hospital length of stay.
Time frame: through patient participation period,180 days maximum
Occurrence of any adverse event during the ICU stay, with a particular focus on hospital or ventilator associated pneumonia, non-respiratory infections, cardiac arrhythmia, and cardiac arrest.
Time frame: through patient participation period,180 days maximum
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 13 Apr 2026.
- Individual participant dataSharing planned: Yes. Data are available upon reasonable request The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients. Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.
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.
29 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing HFNC and CPAP and HFNC in people with De Novo Hypoxemic Acute Respiratory Failure (hARF), run by Assistance Publique - Hôpitaux de Paris at 29 sites in France.
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 16 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 13 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in France. 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 Alexandre DEMOULE (+33 (0)1 42 16 77 61, alexandre.demoule@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mortality (time frame: 90 days). 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 13 Apr 2026.