PRone positioN in Patients With spontanEous ventiLation and Acute Hypoxemic respIratory FailurE (PRONELIFE)

The proposed randomized controlled trial aims at comparing the application of the prone position in spontaneously breathing patients with acute hypoxemic respiratory failure from any cause versus standard treatment on the rate of invasive mechanical ventilation or all-cause of mortality. The secondary endpoints will include time to tracheal intubation and effects of awake proning on the oxygenation parameters, dyspnea sensation, complications, and tolerance. Other endpoints are ventilation free-days at 28 days, duration of invasive ventilation, length of ICU and hospital stay, ICU and hospital mortality, and 28, 60, and 90-day mortality.

The investigators intend to recruit acute hypoxemic respiratory failure patients with a respiratory rate of more than 25 breaths per minute, SpO2 < 94% and FiO2 of at least 40% or more by either Venturi facemask, HFNC, or NIV/CPAP and, absence of decompensated respiratory acidosis during two years. Currently, the investigators expect about 35 centers to participate in the trial. Demographic data and clinical characteristics on screened patients, regardless of enrolment criteria match, will be recorded (registry). The investigators will randomize 650 patients admitted to the participating centers' intensive care units and expect each participating center to randomize at least 25 patients who meet all inclusion criteria.

The best-fitting and most-tolerated oxygen interface will be used in the prone position--this could be different from patient to patient, and different from what is used in the supine position, and could differ between patients but also institutions (i.e., depending on the availability of masks with or without a reservoir bag and with or without the Venturi system, HFNO, CPAP or NIV). The patient will be placed in the prone position for at least 2 hours, which may be prolonged if the patient is comfortable or interrupted if the patient presents any criteria for prone position discontinuation. After the prone position period, the patient will be rotated to the semi-recumbent supine position for at least 2 hours and a maximum of 4 hours. This 2-hour time frame will depend on nursing availability, need for hygiene, complementary explorations, or diet.

Composite endpoint comprising the rate of tracheal intubation or all-cause of mortality during the first fourteen days of enrolment.

Days under the oxygen support device (HFNC, NIV, non-rebreather mask, Venturi mask) The VAS is a straight horizontal line of fixed length. The ends are defined as the extreme limits of the parameter to be measured (symptom,pain,health) orientated from the left (worst) to the right (best).

Effects of prone position on dyspnea, defined according modified Borg dyspnea scale. This is a scale rates the difficulty of breathing. It starts at number 0 where dyspnea is causing no difficulty at all and progresses through to number 10 where dyspnea is maximal.

Effects of prone position on adverse effects such Oxygen desaturations (SpO2 <90%) Episodes of hemodynamic instability (BPsys < 90mmHg or BPsys drop > 10mmHg if BPsys < 90 before the maneuver) Need of orotracheal intubation Cardiac arrest Displacement of the non-invasive respiratory support device Removal of central venous line, if documented Displacement of an arterial line, if documented Displacement of a urinary catheter, if documented

Ventilation-free days (VFD) at 28 days from ICU admission, defined as the number of days alive and free from IMV during the first 28 days from start of IMV

Inclusion criteria >18 years Acute respiratory failure from any cause Admitted to a participating ICU Written informed consent Exclusion criteria Presence of any contraindication to prone position (APPENDIX i) The patient meets the criteria for intubation (see item 7.2.3) Participating in other interventional studies with the same primary outcome Receiving comfort care only Pregnancy

De-identified individual participant data for all primary and secondary outcome measures will be made available

Data access request will be reviewed by an External Independent Review Panel. Requestors will be required to signed a Data Access Agreement

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