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Clinical Trial
. 2025 Oct 23;29(1):448.
doi: 10.1186/s13054-025-05617-y.

Safety and efficacy of inhaled PEG-ADM in ARDS patients: a randomised controlled trial

Christian Karagiannidis  1 , Danny F McAuley  2 , B Taylor Thompson  3 , Thomas Reimer  4 , Kaweh Shakery  4 , Sebastian Schmitz  4 , Manuel Núñez Cortés  4 , Roman Ullrich  5 , Ferhat Meziani  6 , Alain Mercat  7 , Davide Chiumello  8   9   10 , Frantisek Duska  11 , Alain Combes  12   13 ; SEAL Trial Investigators
Collaborators, Affiliations
Clinical Trial

Safety and efficacy of inhaled PEG-ADM in ARDS patients: a randomised controlled trial

Christian Karagiannidis et al. Crit Care. .

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).

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Conflict of interest statement

Declarations. Patient consent and ethical approval: Research involving human participants: This study was conducted in accordance with the consensus ethical principles derived from international guidelines including the Declaration of Helsinki and Council for International Organizations of Medical Sciences (CIOMS) International Ethical Guidelines, as well as applicable International Council for Harmonisation Good Clinical Practice Guidelines and all applicable laws and regulations. The protocol was approved by Institutional Review Boards or Independent Ethics Committees at each study site. Informed consent: Written informed consent was obtained from all capable patients before they were screened for study eligibility. Many of the patients approached for participation had limited decision-making abilities as a result of their critical illness. If a patient was incapable of giving informed consent, consent for study inclusion was sought from authorised representatives according to applicable laws and regulations. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Clinical utility index (CUI) estimates for PEGylated adrenomedullin and placebo. (a) Overall CUI, (b) EVLWi mean treatment effect over Days 4–7, (c) mean percentual reduction in OI from baseline on Days 4–7, and (d) mean change in npSOFA from baseline at Day 7. CI, confidence interval; CUI, clinical utility index; EVLWi, extravascular lung water index; npSOFA, non-pulmonary Sequential Organ Failure Assessment score; OI, oxygenation index; PEG, polyethylene glycol; PEG-ADM, PEGylated adrenomedullin
Fig. 2
Fig. 2
Combined Kaplan–Meyer curve for mortality and Aalen–Johansen curve for onset of ventilator-free survival at Day 60. PEG, polyethylene glycol; PEG-ADM, PEGylated adrenomedullin; VFS, ventilator-free survival
Fig. 3
Fig. 3
Mortality and ventilator status at Days 28 and 60. PEG, polyethylene glycol; PEG-ADM, PEGylated adrenomedullin
See this image and copyright information in PMC

References

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