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Critical Care
Published in: Critical Care 1/2017

Open Access 01-12-2017 | Research

Inhaled AP301 for treatment of pulmonary edema in mechanically ventilated patients with acute respiratory distress syndrome: a phase IIa randomized placebo-controlled trial

Authors: Katharina Krenn, Rudolf Lucas, Adrien Croizé, Stefan Boehme, Klaus Ulrich Klein, Robert Hermann, Klaus Markstaller, Roman Ullrich

Published in: Critical Care | Issue 1/2017

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Abstract

Background

High-permeability pulmonary edema is a hallmark of acute respiratory distress syndrome (ARDS) and is frequently accompanied by impaired alveolar fluid clearance (AFC). AP301 enhances AFC by activating epithelial sodium channels (ENaCs) on alveolar epithelial cells, and we investigated its effect on extravascular lung water index (EVLWI) in mechanically ventilated patients with ARDS.

Methods

Forty adult mechanically ventilated patients with ARDS were included in a randomized, double-blind, placebo-controlled trial for proof of concept. Patients were treated with inhaled AP301 (n = 20) or placebo (0.9% NaCl; n = 20) twice daily for 7 days. EVLWI was measured by thermodilution (PiCCO®), and treatment groups were compared using the nonparametric Mann–Whitney U test.

Results

AP301 inhalation was well tolerated. No differences in mean baseline-adjusted change in EVLWI from screening to day 7 were found between the AP301 and placebo group (p = 0.196). There was no difference in the PaO2/FiO2 ratio, ventilation pressures, Murray lung injury score, or 28-day mortality between the treatment groups. An exploratory subgroup analysis according to severity of illness showed reductions in EVLWI (p = 0.04) and ventilation pressures (p < 0.05) over 7 days in patients with initial sequential organ failure assessment (SOFA) scores ≥11 inhaling AP301 versus placebo, but not in patients with SOFA scores ≤10.

Conclusions

There was no difference in mean baseline-adjusted EVLWI between the AP301 and placebo group. An exploratory post-hoc subgroup analysis indicated reduced EVLWI in patients with SOFA scores ≥11 receiving AP301. These results suggest further confirmation in future clinical trials of inhaled AP301 for treatment of pulmonary edema in patients with ARDS.

Trial registration

The study was prospectively registered at clinicaltrials.gov, NCT01627613. Registered 20 June 2012.
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Metadata
Title
Inhaled AP301 for treatment of pulmonary edema in mechanically ventilated patients with acute respiratory distress syndrome: a phase IIa randomized placebo-controlled trial
Authors
Katharina Krenn
Rudolf Lucas
Adrien Croizé
Stefan Boehme
Klaus Ulrich Klein
Robert Hermann
Klaus Markstaller
Roman Ullrich
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2017
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-017-1795-x

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