Comparison of Non-Invasive Ventilation and High Flow Oxygen Therapy in Reducing Extubation Failure in Patients Undergoing Mechanical Ventilation Weaning

The primary objective of this clinical study is the **reduction of extubation failure** in patients at high risk of extubation failure. This is clinically significant as extubation failure can lead to increased morbidity, prolonged hospital stays, and higher healthcare costs. Addressing this issue is crucial for improving patient outcomes and optimizing resource utilization in healthcare settings.

Secondary objectives include the following:

• Reduction of **reintubation**
• Reduction of **nosocomial infections**
• Reduction of **tracheotomy**
• Reduction of **organ failure**
• Reduction of **ICU stay**
• Reduction of **hospital stay**
• Reduction of **mortality in ICU**
• Reduction of **mortality at 28 days**
• Reduction of **mortality at hospital discharge**
• Reduction of duration of **mechanical ventilation**

The clinical trial focuses on participants experiencing **weaning of mechanical ventilation** with the primary objective of reducing extubation failure. The study population includes both male and female subjects aged 65 years and older. Participants are characterized by specific health conditions such as hypercapnia, ineffective cough, abundant secretions, and a body mass index (BMI) greater than 30. Additionally, individuals with chronic obstructive pulmonary disease (COPD) or asthma, cardiac failure, or a history of ejection fraction less than or equal to 30% are included. The trial also considers those with an Acute Physiology and Chronic Health Evaluation (APACHE II) score greater than 12 at the time of extubation, a history of mechanical ventilation exceeding seven days, positive water balance, and those experiencing difficult or prolonged weaning. Pneumonia or any medical pathology over surgical as a cause of acute respiratory failure (ARF) is also a criterion. The sponsor has not provided the total number of participants or specific lifestyle considerations for this trial. The trial does not involve a vulnerable population.

The clinical trial is designed to evaluate the efficacy of **non-invasive ventilation** (NIV) versus high-flow oxygen therapy (HFOT) in patients at high risk of extubation failure. This is a randomized, double-blind, controlled trial with an estimated duration from September 2024 to September 2027. The primary objective is to reduce extubation failure, with the primary endpoint being the occurrence of acute respiratory failure within 48 hours post-extubation. Secondary endpoints include intubation, nosocomial infection, tracheotomy, organ failure, ICU mortality, hospital mortality, 28-day mortality, ICU length of stay, hospital length of stay, and duration of mechanical ventilation.

Participants will be screened based on specific inclusion criteria, such as age ≥ 65 years, hypercapnia at extubation, ineffective cough, abundant secretions, BMI > 30, chronic obstructive pulmonary disease (COPD) or asthma, cardiac failure, APACHE II > 12, mechanical ventilation > 7 days, positive water balance, difficult or prolonged weaning, and pneumonia as a cause of acute respiratory failure. The trial will exclude any participants not meeting these criteria. The study involves several visits, starting with an inclusion visit to confirm eligibility and obtain informed consent. Follow-up visits will be scheduled to monitor the participants' health status and response to the treatment. The end-of-study visit will assess the final outcomes and gather data for analysis.

The expected length of participant involvement is up to three months, with the possibility of early termination if adverse events occur or if the participant withdraws consent. The trial is categorized as a Phase IV, low-intervention clinical trial, justified by the use of widely accepted respiratory support techniques. The medicinal product used is **oxygen**, administered as a medicinal gas, cryogenic, via inhalation. The maximum daily and total dose is 100%, with a maximum treatment period of three days. The trial aims to provide valuable insights into the optimal respiratory support strategy for patients at risk of extubation failure.

The clinical trial involves the administration of **Oxígeno Medicinal Líquido Air Liquide 99.5% v/v**, a **medicinal gas, cryogenic** formulation. This experimental medication is composed of **oxygen** as the active substance, with a chemical origin. The pharmaceutical form is a cryogenic medicinal gas contained in fixed vessels. The route of administration is via **inhalation gas**. The dosage is set at a maximum daily dose of 100% percent, with the same maximum total dose amount. The treatment period is limited to a maximum of 3 days. The product is not a pediatric formulation and is not classified as an orphan drug. The product is manufactured by Air Liquide Santé International and is authorized for use in Spain.

The efficacy of the clinical trial titled "Non-Invasive Ventilation versus High Flow Oxygenotherapy in Patients at High Risk of Extubation Failure" will be assessed using both primary and secondary endpoints. The primary endpoint is the occurrence of **acute respiratory failure** within 48 hours after extubation. This will be measured to determine the immediate effectiveness of the interventions in preventing extubation failure.

Secondary endpoints include a range of clinical outcomes such as intubation, nosocomial infection, tracheotomy, organ failure, ICU mortality, hospital mortality, 28-day mortality, ICU length of stay, hospital length of stay, and the duration of mechanical ventilation. These endpoints will provide a comprehensive evaluation of the interventions' impact on patient health and recovery.

The trial will compare two respiratory therapies: non-invasive mechanical ventilation (NIV) and high-flow oxygen therapy (HFOT), both of which are established techniques used to prevent extubation failure. The study will involve patients who meet specific inclusion criteria, such as being aged 65 years or older, having **hypercapnia** (paCO2 > 45 mmHg) at the time of extubation, and other clinical conditions that increase the risk of extubation failure.