Treatment with Allogenic Mesenchymal Stromal Cells for Moderate to Severe Acute Respiratory Distress Syndrome: A Double-Blind, Placebo-controlled, Multi-Center, Phase 2b Clinical Trial (STAT).

Summary

In this multicenter, double-blind phase 2b RCT (n=120; 84% COVID-19 ARDS), a single intravenous dose of allogeneic MSCs did not improve the 36-hour oxygenation index or mortality at 14, 28, 60, or 180 days versus placebo. Exploratory plasma proteomics and transcriptomics suggested biologically defined subgroups with differential responses, supporting future biomarker-enriched trials.

Key Findings

• No improvement in the primary endpoint (36-hour oxygenation index change) with MSCs versus placebo.
• No differences in mortality at 14, 28, 60, or 180 days.
• 84% of enrolled patients had COVID-19-related ARDS; baseline severity balanced between groups.
• Plasma protein and gene-expression analyses identified subgroups with differential clinical responses.

Clinical Implications

Single-dose IV MSCs should not be used for ARDS outside trials. Future studies should consider biomarker-enriched populations, dosing strategies (repeat/earlier dosing), and robust phenotyping.

Limitations

• Single-dose regimen; dosing frequency/timing not tested.
• Predominance of COVID-19 ARDS may limit generalizability to non-COVID ARDS.
• Biomarker subgroup findings are exploratory and require validation.

Future Directions

Biomarker-enriched RCTs evaluating alternative MSC dosing (repeat or earlier administration), cell sources, and combinations, with harmonized phenotyping and patient selection.