Evaluation of Inhaled Dornase Alfa Versus Placebo in Reducing Moderate to Severe ARDS Incidence in Ventilated Severe Trauma Patients in ICU

The primary objective of this clinical trial is to demonstrate the efficacy of early intratracheal administration of **dornase alfa** in reducing the incidence of moderate and severe acute respiratory distress syndrome (ARDS) in patients with severe trauma (Injury Severity Score >15) who are hospitalized in the intensive care unit. This is clinically relevant as ARDS is a critical condition that can significantly impact patient outcomes, and reducing its incidence could improve survival rates and decrease the burden on healthcare resources.

Secondary objectives include demonstrating the efficacy of early intratracheal administration of dornase alfa to reduce:

• The incidence of ventilation-acquired pneumonia.
• The impact of multi-organ failure.
• The incidence of minimal respiratory distress syndromes.
• The duration of mechanical ventilation.
• The length of intensive care unit stay.
• The length of hospital stay.
• The mortality rate on day 30.
• Assessment of the safety of dornase alfa administration.

The clinical trial involves a study population of **adult** patients, aged over 18, of both **genders**, who have experienced **severe trauma** with an Injury Severity Score greater than 15. The participants are required to be under mechanical ventilation and admitted to the intensive care unit for less than 6 hours, or less than 18 hours post-arrival at the hospital in cases involving prior surgery or embolization. The trial includes individuals affiliated with the National Health Service, and for women of childbearing age, a negative blood pregnancy test is mandatory. Participants must have an indwelling arterial catheter, and informed consent is obtained from a relative or through an emergency procedure. The sponsor has not provided the total number of participants. The trial population was selected based on these criteria, focusing on those who are vulnerable due to their medical condition. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed as a **randomized**, **double-blind**, controlled study to evaluate the efficacy of early intratracheal administration of **dornase alfa** in reducing the incidence of moderate to severe acute respiratory distress syndrome (ARDS) in patients with severe trauma. The trial will involve adult patients with an Injury Severity Score greater than 15, who are under mechanical ventilation and admitted to the intensive care unit (ICU) within a specified timeframe. The study will compare the effects of inhaled dornase alfa against a placebo, which is **sodium chloride**, both administered via inhalation. The primary endpoint is the incidence of moderate to severe ARDS, defined by specific oxygenation criteria, during the first seven days post-trauma.

The trial is expected to span from March 2019 to September 2027, with participant involvement lasting up to two weeks. The sequence of study visits includes an initial screening visit to confirm eligibility based on inclusion criteria such as age, trauma severity, and ICU admission time. Follow-up visits will occur throughout the treatment period to monitor the patient's response to the intervention and any adverse events. The end-of-study visit will assess the primary endpoint and gather final data on the patient's condition.

Participants may be withdrawn from the study if they experience significant adverse effects, if they withdraw consent, or if they no longer meet the inclusion criteria. The trial's methodology ensures that neither the participants nor the investigators know which treatment the participants receive, maintaining the integrity of the double-blind design. The study aims to provide robust data on the potential benefits of dornase alfa in preventing ARDS in a critically injured population.

The clinical trial involves the administration of **dornase alfa**, marketed under the name Pulmozyme, as the experimental medication. Pulmozyme is provided as a nebuliser solution, specifically formulated as a 2500 U/2.5 ml solution for inhalation via a nebuliser. The active substance, dornase alfa, is a protein-based therapeutic agent classified under the ATC code R05CB13. The medication is administered through inhalation, with a maximum daily dose of 2500 IU and a total maximum dose of 5000 IU over a treatment period of up to 2 days. The administration is intended to be conducted in a controlled clinical setting, ensuring adherence to the dosing schedule and monitoring participant compliance.

The study also includes a non-experimental treatment, which serves as a placebo comparator. This placebo is a **sodium chloride** solution, also administered via inhalation. The sodium chloride solution is provided in a pharmaceutical form suitable for inhalation, with a maximum daily dose of 2.5 ml and a total maximum dose of 5 ml over the same treatment period of up to 2 days. The use of sodium chloride as a placebo is intended to mimic the administration process of the experimental medication without providing the active therapeutic effect, thereby maintaining the double-blind nature of the trial.

The efficacy of the clinical trial will be assessed by evaluating the primary endpoint, which is the incidence of moderate to severe **acute respiratory distress syndrome (ARDS)**. This is defined by a PaO2/FiO2 ratio of ≤ 200 or an SpO2/FiO2 ratio of ≤ 235 if SpO2 is ≤ 97%, according to the 2024 global definition. The trial aims to demonstrate the efficacy of early intratracheal administration of dornase alfa in reducing the incidence of moderate and severe ARDS during the first 7 days post-trauma in patients with severe trauma (Injury Severity Score > 15) who are hospitalized in intensive care.