Study in Intensive Care Patients to Investigate the Clinical Effect of Repetitive Orally Inhaled Doses of AP301 on Alveolar Liquid Clearance in Acute Lung Injury

Inclusion criteria

• age ≥ 18
• intubated and mechanically ventilated male and female patients of the Intensive Care Units of the Department of Anesthesia, General Intensive Care and Pain Control
• meets the criteria of ALI (as defined by the American-European Consensus Conference on ALI/ ARDS):
• Onset of ALI within 48 hours
• Bilateral infiltrates seen on frontal chest radiograph
• PCWP ≤ 18 mm Hg or no clinical evidence of left atrial hypertension
• paO2/ FiO2 ratio ≤ 300 mm Hg
• EVLW in PiCCO® at screening ≥ 8 ml/PBW
• Meeting criteria for extensive hemodynamic monitoring according to investigators discretion
• ICU Patients being mechanically ventilated and are stable in this condition for at least 8 hours
• Negative pregnancy test and adequate contraception in female patients of childbearing potential
• Informed consent:
• For patients that are temporarily unable to consent (e.g. comatose patients) a subsequent informed consent has to be provided.

Exclusion criteria

• History of clinically relevant allergies or idiosyncrasies to AP301 or any other inactive ingredient(s) of the investigational product
• Brainstem death at screening
• Current evidence of septic shock as defined by the Surviving Sepsis Campaign (Presence of acute organ dysfunction secondary to infection plus hypotension with systolic blood pressure < 90 mm Hg or mean arterial pressure (MAP) < 70 mm Hg for not less than one hour which cannot be reversed with fluid resuscitation)
• Neutrophil count <0.3 x 109 L
• Patients under immunosuppression: high dose steroids (> 80 mg Prednisolone /d; > 300 mg hydrocortisone / d), cancer treatment (chemotherapy or biological) or therapy with other immunosuppressive agents for organ transplantation within 2 weeks
• BMI < 18.5 or > 35
• Cardiogenic pulmonary edema diagnosed by echocardiography or pulmonary artery catheter
• Pregnancy / lactation or intention to fall pregnant during the time course of the study
• Women of childbearing potential as well as men of procreative capacity who are not using adequate contraception
• Participation in other interventional drug trials