Br J Clin Pharmacol. 2022 Jan 4. doi: 10.1111/bcp.15212. Online ahead of print.
ABSTRACT
OBJECTIVE: To determine the safety and efficacy-potential of inhaled nebulised unfractionated heparin (UFH) in the treatment of hospitalised patients with COVID-19.
METHODS: Retrospective, uncontrolled multicentre single-arm case series of hospitalised patients with laboratory-confirmed COVID-19, treated with inhaled nebulised UFH (5000IU 8-hourly, 10000IU 4-hourly, or 25000IU 6-hourly) for 6±3 (mean±SD) days. Outcomes were APTT before treatment (baseline) and highest-level during treatment (peak), and adverse events including bleeding. Exploratory efficacy outcomes were oxygenation, assessed by SpO2 to FiO2 (S/F) ratio and FiO2, and the WHO modified ordinal clinical scale (MOCS).
RESULTS: 98 patients were included. In patients on stable prophylactic or therapeutic systemic anticoagulant therapy but not receiving therapeutic UFH infusion, APTT levels increased from baseline of 34±10 seconds to a peak of 38±11 seconds (p<0.0001). In 3 patients on therapeutic UFH infusion, APTT levels did not significantly increase from baseline of 72±20 to a peak of 84±28 seconds (p=0.17). Two patients had serious adverse events: bleeding gastric ulcer requiring transfusion; thigh haematoma; both were on therapeutic anticoagulation. Minor bleeding occurred in 16 patients, 13 of which were on therapeutic anticoagulation. The S/F ratio and the FiO2 worsened before and improved after commencement of inhaled UFH (change in slope, p<0.001).
CONCLUSION: Inhaled nebulised UFH in hospitalised patients with COVID-19 was safe. Although statistically significant, inhaled nebulised UFH did not produce a clinically relevant increase in APTT (peak values in the normal range). Urgent randomised evaluation of nebulised UFH in patients with COVID-19 is warranted and several studies are currently underway.
PMID:34984714 | DOI:10.1111/bcp.15212
