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

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

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.

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

Researchers who provide a methodologically sound proposal.