Clinical trial NCT06213168: 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.
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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: De Novo Hypoxemic Acute Respiratory Failure (hARF)
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
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2024-01-19
Enrollment: 1084
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: BASIC_SCIENCE

Brief 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. 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


Eligibility criteria: 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
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
9. 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

Primary outcomes:
measure: Mortality
timeFrame: 90 days
Secondary outcomes:
measure: Time from randomization to intubation.
timeFrame: 28 days
measure: Intensity of dyspnea until intubation as assessed by a visual analogic scale from zero (no dyspnea) to 100 (maximum possible dyspnea).
timeFrame: 2, 6, 12 and 24 hours
measure: Respiratory rate
timeFrame: 6, 12 and 24 hours
measure: ROX index
timeFrame: 6, 12 and 24 hours
measure: Evaluation of intolerance to oxygenation technique until intubation
timeFrame: 12 and 24 hours
measure: Discomfort associated with the interface as assessed by a visual analogic scale from zero (no discomfort) to 100 (maximum possible discomfort).
timeFrame: 12 and 24 hours
measure: Level of oxygenation assessed by blood gas that will be sampled on the request of the physician in charge (clinical purpose only).
timeFrame: First 24 hours or until intubation
measure: Use of NIV for one of the following predefined indication criteria.
timeFrame: through study completion
measure: Death within the ICU
timeFrame: through patient participation period,180 days maximum
measure: Time to death
timeFrame: through patient participation period, an average of 180 days maximum
measure: Death within the hospital and time to death.
timeFrame: through patient participation period,180 days maximum
measure: Number of invasive ventilation-free days at 28 days defined as days alive and without intubation.
timeFrame: Between day 1 and day 28
measure: Number of HFNC-free days at 28 days defined as days non-intubated, alive and without HFNC.
timeFrame: Between day 1 and day 28.
measure: ICU length of stay.
timeFrame: through patient participation period,180 days maximum
measure: Hospital length of stay.
timeFrame: through patient participation period,180 days maximum
measure: 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.
timeFrame: through patient participation period,180 days maximum
Other outcomes:
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