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

Summary

In a multicenter phase 2 randomized, double-blind trial (n=90), inhaled pegylated adrenomedullin showed safety comparable to placebo but did not improve a composite clinical utility index or 28-day ventilator-free survival. Mortality and ongoing ventilation at days 28 and 60 were not different; the trial was stopped early for futility.

Key Findings

• Both PEG-ADM doses were well tolerated with adverse events similar to placebo.
• No improvement in the composite clinical utility index was observed versus placebo.
• 28-day ventilator-free survival was lower in the 960 μg group (52%) versus 1920 μg (67%) and placebo (65%).
• No significant differences in mortality or need for ongoing ventilation at days 28 and 60; early futility termination.

Clinical Implications

Do not adopt inhaled pegylated adrenomedullin for ARDS outside research. Focus clinical practice on proven supportive strategies and consider phenotypic enrichment in future trials.

Limitations

• Phase 2 sample size (n=90) may limit power to detect modest benefits.
• Heterogeneity of ARDS etiologies and care practices could dilute treatment effects; early stopping limits longer-term assessment.

Future Directions

Consider alternative delivery or systemic dosing of adrenomedullin, phenotype-enriched enrollment, and endpoints aligned with specific ARDS subphenotypes in larger phase 3 trials.