Efficacy of inhaled nebulised unfractionated heparin to prevent intubation or death in hospitalised patients with COVID-19: an investigator-initiated international meta-trial of randomised clinical studies.

Summary

In a prospective collaborative meta-trial pooling six randomized clinical studies across six countries (n=478), inhaled nebulised unfractionated heparin reduced the composite of intubation or death (OR 0.43, 95% CI 0.26–0.73; p=0.001) and lowered in-hospital mortality (OR 0.26, 95% CI 0.13–0.54; p<0.001), without pulmonary or systemic bleeding.

Key Findings

• Reduced intubation or death with nebulised UFH vs. standard care (OR 0.43, 95% CI 0.26–0.73; p=0.001)
• Lower in-hospital mortality with nebulised UFH (OR 0.26, 95% CI 0.13–0.54; p<0.001)
• No pulmonary or systemic bleeding events reported in the UFH group
• Prospective, pre-specified collaborative meta-trial across six countries (n=478)

Clinical Implications

Consider implementing nebulised UFH within protocolized pathways for hospitalized, non-intubated COVID-19 patients at risk of deterioration, while standardizing dosing/nebulization and monitoring for bleeding; further trials should evaluate generalizability to non-COVID ARDS.

Limitations

• Heterogeneity in UFH dosing and nebulisation methods across contributing trials
• Evidence limited to COVID-19-related respiratory failure; generalizability to non-COVID ARDS uncertain

Future Directions

Head-to-head randomized trials to standardize dosing, delivery devices, and timing; evaluation in non-COVID ARDS and phenotype-specific subgroups; mechanistic studies on antiviral, anti-inflammatory, and antithrombotic effects in vivo.