Aprotinin Treatment of Acute Respiratory Distress Syndrome: a Multicenter, Double-blind, Placebo-controlled, Phase III Trial
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.
⁃ Each potential participant must satisfy all of the following criteria to be enrolled in the study:
• Diagnosed with moderate or severe Acute Respiratory Distress Syndrome (ARDS) according to the Berlin definition (ARDS Definition Task Force 2012):
‣ 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.
⁃ Hypoxemia:
• Moderate ARDS: PaO₂/FiO₂ \>100 mmHg and ≤200 mmHg with Positive End-Expiratory Pressure (PEEP) ≥5 cmH₂O.
∙ Severe ARDS: PaO₂/FiO₂ ≤100 mmHg with PEEP ≥5 cmH₂O.
• Radiographic and hypoxemia criteria must occur within the same 24-hour period. ARDS onset is defined as the time when the last of these two criteria is met.
• First dose of study drug planned within 48 hours of moderate or severe ARDS diagnosis.
• Intubated and receiving mechanical ventilation.
• Age ≥18 years.
• Women of childbearing potential must have a negative serum pregnancy test during screening and a negative urine pregnancy test at study start. Female subjects of childbearing potential and male subjects with partners of childbearing potential must agree to use an effective contraceptive method from consent until 30 days after study drug administration.