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. (HighCPAP)

April 7, 2026 updated by: Assistance Publique - Hôpitaux de Paris

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

1084

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Amiens, France, 80054
      • Angers, France, 49933
      • Argenteuil, France, 95107
      • Bobigny, France, 93000
        • Not yet recruiting
        • Hopital Avicenne
        • Contact:
      • Bourg-en-Bresse, France, 01012
        • Recruiting
        • Centre Hospitalier de Bourg-en-Bresse - Site de Fleyriat
        • Contact:
      • Colombes, France, 92700
        • Not yet recruiting
        • Hôpital Louis-Mourier
        • Contact:
      • Corbeil-Essonnes, France, 91100
        • Not yet recruiting
        • Centre Hospitalier Sud Francilien
        • Contact:
      • Créteil, France, 94010
      • Dieppe, France, 76200
        • Recruiting
        • Centre Hospitalier de Dieppe - Site Pasteur
        • Contact:
      • Dijon, France, 21000
      • Le Chesnay, France, 78157
        • Recruiting
        • Hôpital André Mignot
        • Contact:
      • Le Kremlin-Bicêtre, France, 94270
        • Not yet recruiting
        • Hôpital Bicêtre
        • Contact:
      • Le Mans, France, 72037
        • Recruiting
        • Centre Hospitalier du Mans
        • Contact:
      • Lille, France, 59037
      • Lyon, France, 69007
      • Lyon, France, 69003
        • Recruiting
        • Hôpital Edouard Herriot - Hospices Civils de Lyon
        • Contact:
      • Lyon, France, 69004
        • Recruiting
        • Hôpital de la Croix-Rousse - Hospices Civils de Lyon
        • Contact:
      • Lyon, France, 69495
        • Not yet recruiting
        • Hôpital Lyon Sud - Hospices Civils de Lyon
        • Contact:
      • Montpellier, France, 34090
      • Nantes, France, 44000
      • Nice, France, 06000
        • Active, not recruiting
        • Hôpital Pasteur
      • Nice, France, 06200
        • Recruiting
        • Hôpital de l'Archet
        • Contact:
      • Paris, France, 75012
        • Recruiting
        • Hopital Saint-Antoine
        • Contact:
      • Paris, France, 75020
      • Paris, France, 75013
        • Recruiting
        • APHP - hôpital Pitié-Salpêtrière
        • Contact:
      • Poitiers, France, 86000
      • Rennes, France, 35000
      • Rouen, France, 76000
      • Strasbourg, France, 67000

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Adults (≥ 18 years old)
  2. Admitted in the ICU for ≤ 24 hours

  3. De novo hARF defined by the three following criteria:

    1. Respiratory rate > 25 breaths/min or signs of respiratory distress such as labored breathing or paradoxical inspiration
    2. PaO2/FiO2 ≤ 200 mmHg under HFNC with flow ≥ 45 L/min, actual FiO2 being considered.
    3. Uni or bilateral pulmonary infiltrate on chest X-ray or CT scan
  4. 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

Exclusion Criteria:

  1. Refusal of study participation by the patient or the proxy
  2. Anatomical factors precluding the use of a nasal cannula or CPAP
  3. Long term oxygen
  4. Home CPAP or NIV or CPAP or NIV initiated prior to ICU admission
  5. Hypercapnia indicating NIV (PaCO2 > 45 mmHg)
  6. Isolated cardiogenic pulmonary oedema indicating NIV
  7. Known pregnancy or breastfeeding
  8. Absence of coverage by the French statutory health care insurance system (including AME)
  9. Abdominal, thoracic or cardiac surgery within the last 6 days
  10. Use of vasopressors (norepinephrine>0.3 mcg/kg/min)
  11. Glasgow coma scale < 13
  12. Urgent need for endotracheal intubation
  13. Patients at an end-of-life stage receiving compational oxygenation
  14. Exacerbation of a chronic respiratory disease
  15. Legal protection (curatorship or tutorship)
  16. Undrained pneumothorax

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: HFNC
Patients assigned to the control group will be continuously treated by HFNC. HFNC will be initiated within one hour following randomization.
Other: HFNC
Patients assigned to the control group will be continuously treated by HFNC. HFNC will be initiated within one hour following randomization
Other Names:
  • High flow nasal cannula oxygen therapy
Experimental: HFNC with CPAP
Patients assigned to the intervention group will receive high flow nasal oxygen plus CPAP sessions
Other: HFNC
Patients assigned to the control group will be continuously treated by HFNC. HFNC will be initiated within one hour following randomization
Other Names:
  • High flow nasal cannula oxygen therapy
Other: CPAP and HFNC
Patients assigned to the intervention group will receive high flow nasal oxygen plus CPAP sessions
Other Names:
  • Continuous positive airway pressure and High flow nasal canulae

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mortality
Time Frame: 90 days
Time to death within the 90 days after randomization
90 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time from randomization to intubation.
Time Frame: 28 days
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
2, 6, 12 and 24 hours
Respiratory rate
Time Frame: 6, 12 and 24 hours
6, 12 and 24 hours
ROX index
Time Frame: 6, 12 and 24 hours
6, 12 and 24 hours
Evaluation of intolerance to oxygenation technique until intubation
Time Frame: 12 and 24 hours
evaluation based on the following physical criteria: eyes dryness, nose dryness and/or feeling of gastric distention
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
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
First 24 hours or until intubation
Use of NIV for one of the following predefined indication criteria.
Time Frame: through study completion
  1. the constitution of a clear indication such as acute-on-chronic respiratory failure with respiratory acidosis (pH < 7.35) or acute cardiogenic pulmonary edema,
  2. pre oxygenation before intubation,
  3. fiberoptic bronchoscopy.
through study completion
Death within the ICU
Time Frame: through patient participation period,180 days maximum
through patient participation period,180 days maximum
Time to death
Time Frame: through patient participation period, an average of 180 days maximum
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
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
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.
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.
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.
Between day 1 and day 28.
ICU length of stay.
Time Frame: through patient participation period,180 days maximum
through patient participation period,180 days maximum
Hospital length of stay.
Time Frame: through patient participation period,180 days maximum
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
through patient participation period,180 days maximum

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 19, 2025

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

March 1, 2027

Study Registration Dates

First Submitted

December 18, 2023

First Submitted That Met QC Criteria

January 9, 2024

First Posted (Actual)

January 19, 2024

Study Record Updates

Last Update Posted (Actual)

April 13, 2026

Last Update Submitted That Met QC Criteria

April 7, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • APHP220813

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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.

IPD Sharing Time Frame

Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor

IPD Sharing Access Criteria

Researchers who provide a methodologically sound proposal.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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