LATE-BREAKING ABSTRACT: Prospective randomised pilot study to investigate the clinical effect of orally inhaled AP301 on treatment of primary graft dysfunction (PGD) in patients after primary lung transplantation (LuTX)

Abstract

Background: PGD following LuTX carries significant morbidity and mortality. AP301, an activator of ENaC-mediated Na(+) uptake represents a new concept for treatment of hyper-permeability oedema with promising preclinical results.

Aims: This study aims to investigate the effect of AP301 on patients with PGD≥1 at ICU arrival after LuTX.

Methods: Prospective randomised, placebo-controlled pilot-study. All patients fulfilling inclusion criteria are screened for PGD at ICU arrival. After randomization AP301 or placebo is administered via nebulizer twice daily for 7 days or until extubation. Otherwise patients are treated according to clinical routine protocol and followed for 30 days within the study.

Results: From 7/2013-8/2014 20 patients were randomised 1:1 to AP301 (group 1) or placebo (group 2). Demographics were comparable in both groups as well as mean PaO2/FiO2 ratio at time of inclusion (236±91 vs 214±96). Patients in group 1 had a significantly shorter duration of intubation with 2±0,8 vs 3,7±2 days (p=0,02). There was a trend towards a shorter ICU stay (7,5±3,1 vs 10,8±8,7 days) and increased PaO2/FiO2 ratio in group 1 at 24h (313±126 vs 240±90), 48h (486±59 vs 460±33), 72h (504±40 vs 427±78) and 96h postoperative (549±0 vs 370±96). Thereafter no patient in group 1 was ventilated. 30-day survival was 100%.

Conclusion: This pilot study showed impressive clinical effects of AP301 on patients with PGD after primary LuTX leading to a significantly shorter intubation time and a trend towards improved gas exchange and shorter ICU stay. Further investigation of AP301 for PGD treatment is warranted.