This is a multicentre, double-blind, placebo-controlled Phase III randomized clinical trial designed to evaluate the efficacy and safety of inhaled aprotinin in adult patients with moderate or severe acute respiratory distress syndrome (ARDS). A total of 156 critically ill patients admitted to intensive care units will be randomized to receive either inhaled aprotinin or placebo in addition to standard supportive care. The primary objective is to determine whether aprotinin improves clinical outcomes based on a composite endpoint of ventilator-free days at 28 days.
Acute onset of respiratory failure within 1 week of a known clinical insult or new/worsening respiratory symptoms.
Respiratory failure not fully explained by cardiac failure or fluid overload; objective evaluation of cardiac failure or fluid overload is required if ARDS risk factors are absent.
Radiographic abnormalities on chest X-ray or CT scan: bilateral opacities not fully explained by effusions, nodules, masses, or lobar/segmental collapse.
Moderate ARDS: PaO₂/FiO₂ >100 mmHg and ≤200 mmHg with Positive End-Expiratory Pressure (PEEP) ≥5 cmH₂O.
Pregnant or lactating women, or positive/indeterminate pregnancy test (serum or urine).
Simultaneous participation in another pharmacotherapy protocol.
Life expectancy <24 hours.
Clinical condition in which, in the investigator's opinion, ventilator withdrawal is extremely unlikely (e.g., motor neuron disease, Duchenne muscular dystrophy, rapidly progressive interstitial lung disease).
Parallel
Aprotinin (inhaled)
DrugInhaled aprotinin, diluted in 0.9% sodium chloride, is administrated via nebulization through an endotracheal or tracheostomy tube. The dose is 500 UI every 6 hours (totaling 2,000 UI/day) for six consecutive days. Each administration consists of a nebulized inhalation lasting no less than six minutes, with four inhalations delivered per day. Nebulization is performed using Aerogen® Solo vibrating mesh nebulizers to maintain a closed ventilatory circuit. The device produces aerosol particles with a median diameter of 2-10 µm; 30-50% of these aggregates reach diameters of 50-100 µm. Administration follows pharmacy blinding procedures. All patients receive standard supportive care according to local practice.
Placebo (Sodium Chloride)
DrugPlacebo (sodium chloride) is administered by inhalation via endotracheal or tracheostomy tube using the Aerogen® Solo vibrating mesh nebulizer, four times daily for six consecutive days. It is delivered following the same dosing schedule, device specifications, and administration procedures as the active treatment. Administration follows pharmacy blinding procedures to maintain double-blind conditions. All patients receive standard supportive care according to local practice.
Ventilator-Free Days (VFD) in patients with moderate or severe ARDS
Number of days a patient is free from invasive mechanical ventilation (DLVI) within 28 days after first dose. A patient is considered ventilator-free after two consecutive calendar days of unassisted breathing. This outcome will be used to assess the efficacy of inhaled aprotinin compared with placebo.
Number of participants with at least one treatment-emergent adverse event
Incidence, severity, and relationship to treatment of adverse events (AEs), coded according to MedDRA (Medical Dictionary for Regulatory Activities), in treated participants. This outcome evaluates the safety profile of aprotinin compared with placebo.
Proportion of patients who die from any cause within 28, 90, or 180 days after receiving first dose of study treatment.
All-Cause Mortality.
Number of days free from ICU or hospital
Total number of days a patient remains outside the intensive care unit (ICU) and outside the hospital within 28 days after receiving first dose of study treatment.
Number of days on renal or vasoactive support within 28 days after first dose
Total number of days a patient requires renal replacement therapy or vasoactive support within 28 days after receiving first dose of study treatment.
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