Evaluation of Apneic Oxygenation with High-Flow Nasal Oxygenation Post-Noninvasive Ventilation Preoxygenation in Hypoxemic Acute Respiratory Failure Patients

The primary objective of this study is to evaluate whether **apneic oxygenation** with high-flow nasal oxygenation (HFNO) reduces the incidence of severe hypoxemia compared to no apneic oxygenation during the intubation procedure in patients with hypoxemic acute respiratory failure. This is clinically relevant as severe hypoxemia during intubation can lead to significant morbidity and mortality, and improving oxygenation strategies could enhance patient outcomes in critical care settings.

Secondary objectives include: - Comparing the incidence of prolonged severe hypoxemia between the two groups during the procedure. - Measuring the highest and lowest SpO2 values during the procedure. - Assessing the incidence of immediate severe complications, such as cardiovascular instability, cardiac arrest, and new onset cardiac arrhythmias. - Evaluating the incidence of other adverse events, including difficult intubation, operator-reported aspiration, dental injury, esophageal intubation, and pneumothorax. - Determining the duration of laryngoscopy and the number of laryngoscopies. - Monitoring mortality at day 28.

The clinical trial involves participants diagnosed with **hypoxemic acute respiratory failure**. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically includes adults and older adults. Participants are selected based on their admission to the ICU with an indication for orotracheal intubation and must exhibit signs of acute respiratory distress, such as a respiratory rate greater than 25/min, dyspnea, or the use of accessory respiratory muscles. Additionally, a PaO2/FiO2 ratio of 200 mmHg or less is required within six hours before the decision for intubation. The trial population is considered vulnerable, and informed consent is obtained from patients or their relatives, with emergency procedures available if necessary. The sponsor has not provided the total number of participants involved in the study. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of **apneic oxygenation** using high-flow nasal oxygenation in patients with **hypoxemic acute respiratory failure** during the intubation process in an intensive care unit setting. This is a multicenter, randomized, controlled trial with a double-blind design to ensure unbiased results. The trial aims to assess whether this method decreases the incidence of severe hypoxemia compared to no apneic oxygenation during the intubation procedure. The study is expected to commence on September 15, 2025, and conclude by October 15, 2028, with a total duration of approximately three years.

Participants will undergo a series of study visits, beginning with an inclusion visit where eligibility is confirmed based on criteria such as admission to the ICU, indication for orotracheal intubation, and the presence of hypoxemic acute respiratory failure. Informed consent will be obtained from the patient or their relatives, with emergency procedures available if necessary. Follow-up visits will be conducted to monitor the incidence of severe hypoxemia, defined as an oxygen saturation (SpO2) below 80% from the start of laryngoscopy to five minutes post-intubation. Secondary endpoints include the duration of hypoxemia, the highest and lowest SpO2 values, and the occurrence of severe complications such as cardiovascular instability and cardiac arrest.

The expected length of participant involvement is limited to the duration of the intubation procedure and immediate post-procedure monitoring. Conditions that may lead to early termination from the study include withdrawal of consent or the occurrence of adverse events that compromise patient safety. The trial will utilize **oxygen** as a medicinal gas for inhalation, with a maximum daily dose of 60 liters and a total dose not exceeding 70 liters. The trial is categorized as a low-intervention study, ensuring minimal risk to participants while providing valuable insights into the management of hypoxemic acute respiratory failure.

The clinical trial involves the use of **OXYGENE MEDICINAL LIQUIDE AIR LIQUIDE SANTE FRANCE**, a medicinal gas for inhalation, specifically designed for use with a fixed evaporator. The active substance in this experimental treatment is **oxygen**, which is of chemical origin. The pharmaceutical form of the product is a **medicinal gas, cryogenic**, and it is administered via the **inhalation gas** route. The maximum daily dose is 60 liters, with a total maximum dose of 70 liters over the course of the treatment period, which is limited to one day. The product is not a pediatric formulation and is not classified as an orphan drug. The administration of the gas is intended to provide apneic oxygenation during the intubation procedure in patients with hypoxemic acute respiratory failure.

In this study, there are no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments mentioned. The focus is solely on the administration of the experimental medicinal gas. Participant compliance with the dosing schedule will be monitored to ensure adherence to the protocol. The trial aims to evaluate the efficacy of high-flow nasal oxygenation in reducing the incidence of severe hypoxemia during the intubation process.

Efficacy in this clinical trial will be assessed by evaluating the primary and secondary endpoints related to the incidence and severity of **hypoxemia** during the intubation procedure in patients with hypoxemic acute respiratory failure. The primary endpoint is the incidence of severe hypoxemia, defined as at least one episode of oxygen saturation (SpO2) measured by pulse oximetry falling below 80% from the start of laryngoscopy to 5 minutes after successful intubation. Secondary endpoints include the incidence of prolonged severe hypoxemia, characterized by SpO2 remaining below 80% for more than 24 seconds within the same timeframe, as well as the highest and lowest SpO2 values recorded during the procedure.

Additional secondary endpoints involve the occurrence of immediate severe complications such as cardiovascular instability, cardiac arrest, and new onset cardiac arrhythmias. Other adverse events, including difficult intubation, operator-reported aspiration, dental injury, esophageal intubation, and pneumothorax, will also be monitored. The duration of laryngoscopy and the number of attempts required for successful intubation will be compared between groups. Vital status at day 28 post-procedure will be assessed to provide further insights into the efficacy of the intervention. These parameters will be measured and collected using validated clinical methods and tools, ensuring accurate and reliable data for analysis.