TY - JOUR T1 - Oral inhalation of AP301 peptide activates pulmonary oedema clearance: Initial results from a phase IIa clinical trial in mechanically ventilated ICU patients JF - European Respiratory Journal JO - Eur Respir J VL - 44 IS - Suppl 58 SP - 1386 AU - Katharina Krenn AU - Adrien Croize AU - Klaus Ulrich Klein AU - Stefan Böhme AU - Klaus Markstaller AU - Roman Ullrich AU - Robert Hermann AU - Rudolf Lucas AU - Bernhard Fischer Y1 - 2014/09/01 UR - http://erj.ersjournals.com/content/44/Suppl_58/1386.abstract N2 - Acute pulmonary permeability oedema is a major component of Acute Lung Injury (ALI). AP301, a synthetic peptide structurally based on the lectin-like domain of human TNFα has been designed to activate pulmonary oedema clearance by activating the sodium ion channel (ENaC) in pulmonary epithelial cells.A randomized, double-blind, placebo-controlled, parallel-group proof of concept study was performed on 40 mechanically ventilated adult male and female patients with ALI. Every 12 hours for 7 days, 20 patients inhaled aerosolized AP301 (verum group) and 20 patients inhaled saline (placebo group). Reduction of pulmonary oedema (primary objective) was determined by measurement of the extra-vascular lung water (EVLW) content by PiCCO® technique twice daily. PaO2/FiO2 ratio was assessed once daily as part of the enhanced hemodynamic monitoring. Lung function and vital signs were measured regularly for diagnostic and safety assessment.Oral inhalation of AP301 by patients led to an earlier onset and more pronounced activation of pulmonary oedema clearance compared to placebo treated patients. Subgroup analysis revealed that oral inhalation of AP301 was even more effective in pulmonary oedema clearance in patients with a higher sequential organ failure assessment (SOFA) score and patients with initial PaO2/FiO2-ratio 100-200, if compared to placebo treated patients. Oral inhalation of AP301 led to an earlier onset and more pronounced increase in oxygenation index compared to placebo treatment.The alveolar clearance effect of AP301 was shown to be favourable, and thereby supports further clinical development of AP301. ER -