Can nebulised heparin reduce acute lung injury in patients with SARS‑CoV‑2 requiring advanced respiratory support in Ireland: the CHARTER‑Ireland phase Ib/IIa, randomised, parallel-group, open-label study.

Summary

In this multicenter randomized open-label phase Ib/IIa trial (n=40), nebulised unfractionated heparin did not reduce D-dimer over 10 days and was associated with worse oxygenation in COVID-19 ARDS, despite an acceptable safety profile without severe bleeding or HIT.

Key Findings

• No significant reduction in D-dimer from baseline to day 10 with nebulised heparin versus standard care (p=0.996).
• Acceptable safety profile: more bleeding events in the heparin group but no pulmonary bleeding, severe hemorrhage, or HIT.
• Patients receiving heparin had worse oxygenation indices (lower PaO2/FiO2).

Clinical Implications

Nebulised unfractionated heparin should not be used routinely in COVID-19 ARDS outside trials, given lack of biomarker benefit and worsened oxygenation; careful monitoring for bleeding remains prudent.

Limitations

• Open-label design with small sample size (n=40) likely underpowered for clinical outcomes.
• COVID-19-specific context and surrogate primary endpoint (D-dimer) limit generalizability to non-COVID ARDS and hard outcomes.

Future Directions

Conduct adequately powered, blinded RCTs testing inhaled anticoagulants with hard clinical endpoints and stratification by thrombosis phenotype; evaluate non-COVID ARDS populations.