Summary of COVID-19 inhaled heparin studies

1. van Haren et al., 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

478 patient inhaled heparin late treatment RCT: 58% lower mortality (p=0.01), 47% lower ventilation (p=0.01), and 23% lower hospitalization (p=0.02).
Meta-trial of 6 RCTs with 478 hospitalized COVID-19 patients showing significant benefit with inhaled nebulized unfractionated heparin (UFH). Patients receiving nebulized UFH had lower rates of intubation or death at longest follow-up (11.2% vs 22.4%, OR 0.43, p=0.001) and lower in-hospital mortality (4.3% vs 14.3%, OR 0.26, p<0.001). Authors hypothesize the benefits result from UFH's combined antiviral, anti-inflammatory, and anticoagulant properties that prevent viral entry, reduce lung injury progression, and limit pulmonary thrombosis.
Oct 2025, eClinicalMedicine, https://www.sciencedirect.com/science/article/pii/S2589537025002718, https://c19p.org/vanharen

2. DeNucci et al., Inhaled nebulised unfractionated heparin (UFH) for the treatment of hospitalised patients with COVID-19: A randomised controlled pilot study

76 patient inhaled heparin late treatment RCT: 42% lower mortality (p=0.27), 42% lower ventilation (p=0.27), and 5% shorter hospitalization (p=0.8).
RCT 75 hospitalized patients with COVID-19 showing reduced mortality with inhaled nebulized unfractionated heparin (UFH).
Jun 2023, Pulmonary Pharmacology & Therapeutics, https://www.sciencedirect.com/science/article/pii/S109455392300024X, https://c19p.org/denucci

3. Smith et al., A randomised, open-label trial of nebulised unfractionated heparin in patients mechanically ventilated for COVID-19

50 patient inhaled heparin ICU RCT: 70% higher mortality (p=1).
RCT 50 intubated COVID-19 patients showing no improvement with inhaled nebulized unfractionated heparin. Time to separation from invasive ventilation among survivors to day 28 was significantly slower in the heparin group.
Mar 2025, Anaesthesia and Intensive Care, https://journals.sagepub.com/doi/10.1177/0310057X251322783, https://c19p.org/smith5

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