Year: 2025
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: BACKGROUND: This study aimed to evaluate the safety and efficacy of inhaled pegylated adrenomedullin (PEG-ADM) for the management of acute respiratory distress syndrome in critically ill patients on mechanical ventilation. METHODS: A Phase 2a/b randomised, double-blind, placebo-controlled multicentre trial was conducted. Patients with acute respiratory distress syndrome were assigned to receive PEG-ADM 960 μg or 1920 μg, or placebo. The primary endpoints were safety, efficacy, and ventilator-free survival at Day 28. Efficacy was assessed using ventilator-free survival and the clinical utility index, a composite endpoint that includes extravascular lung water index, oxygenation index, non-pulmonary Sequential Organ Failure Assessment score. RESULTS: Ninety patients were randomised (PEG-ADM 960 μg: n = 29; PEG-ADM 1920 μg: n = 30; placebo: n = 31). Both dosages of PEG-ADM were well tolerated, with adverse event profiles similar to placebo. However, no significant efficacy was observed on the clinical utility index. Ventilator-free survival at Day 28 was lower in the PEG-ADM 960 μg group (52%) compared with the PEG-ADM 1920 μg (67%) and placebo (65%) groups. No significant differences were noted in overall mortality or the need for continued ventilation at Days 28 and 60. CONCLUSION: Inhaled PEG-ADM was well tolerated in patients with acute respiratory distress syndrome, but it did not improve clinical outcomes, which led to the early discontinuation after the first part of the trial for futility. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04417036 (date of registration: 4 June 2020).
Source: Critical Care
Authors: Christian Karagiannidis, Danny F. McAuley, B. Taylor Thompson, Thomas Reimer, Kaweh Shakery, Sebastian Schmitz, Manuel Núñez Cortés, Roman Ullrich, Ferhat Meziani, Alain Mercat, Davide Chiumello, Frantisek Duska, Alain Combes, for the SEAL Trial Investigators, Christian Karagiannidis, Danny F. McAuley, B. Taylor Thompson, Thomas Reimer, Kaweh Shakery, Sebastian Schmitz, Manuel Núñez Cortés, Roman Ullrich, Ferhat Meziani, Alain Mercat, Davide Chiumello, Frantisek Duska, Alain Combes, Katharina Krenn, Philipp Eller, Michael Joannidis, Michael Joannidis, Herbert Koinig, Roman Skulec, Vladimir Cerny, Jan Berousek, Frédéric Pene, Jean-Daneil Chiche, Laurent Papazian, Sami Hraiech, Nicolas Terzi, Ulf Günther, Tobias Welte, Martin Witzenrath, Norbert Weiler, Marc Berger, Giacomo Grasselli, Antoni Betbese Roig, Candelaria de Haro Lopez, Ana Ochagavia Calvo, Ricardo Ferrer Roca, Rafael Mañez Mendiluce, Jeremy Bewley, Andrew Aswani, Ingeborg Welters, Matthew Wise, Robert Jackson
Institutions: Witten/Herdecke University, Queen's University Belfast, Harvard University, Massachusetts General Hospital, Bayer (Germany), Hôpitaux Universitaires de Strasbourg, Hôpital Civil, Strasbourg, Centre Hospitalier Universitaire d'Angers, Université d'Angers, University of Milan, Azienda Socio Sanitaria Territoriale Santi Paolo e Carlo, Charles University, Inserm, Sorbonne Université, Assistance Publique – Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Fondation pour l’innovation en Cadiométabolisme et Nutrition
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,190
Funder: Bayer
OpenAlex ID: W4415468864