Inhaled nebulised unfractionated heparin for the treatment of hospitalised patients with COVID-19: A multicentre case series of 98 patients

TY - JOUR

T1 - Inhaled nebulised unfractionated heparin for the treatment of hospitalised patients with COVID-19

T2 - A multicentre case series of 98 patients

AU - van Haren, Frank M.P.

AU - van Loon, Lex M.

AU - Steins, Anne

AU - Smoot, Thomas L.

AU - Sas, Caitlin

AU - Staas, Sabrina

AU - Vilaseca, Alicia B.

AU - Barbera, Ruben A.

AU - Vidmar, Gustavo

AU - Beccari, Hugo

AU - Popilevsky, Frida

AU - Daribayeva, Eleonora

AU - Venkatesan, Bhuvaneshwari

AU - Mozes, Susan

AU - Postel, Rachel

AU - Popilevski, Natalie

AU - Webb, Andrew

AU - Nunes, Quentin

AU - Laffey, John G.

AU - Artigas, Antonio

AU - Smith, Roger

AU - Dixon, Barry

AU - Richardson, Alice

AU - Yoon, Hwan Jin

AU - Page, Clive

N1 - Funding Information: A.A. reports a research grant for preclinical research from Grifols and from Fisher & Paykel, and payment as Scientific Advisor for Grifols, outside the submitted work. J.L. reports receiving an Academic Collaboration grant funded by Science Foundation Ireland and Aerogen Inc. for a different, but related, clinical study (CHARTER‐Ireland). C.P. reports receiving personal fees from Cipla, Immune Regulation, EpiEndo and Glycosynnovation, and has equity in Verona Pharma, outside of the submitted work. All other authors have nothing to disclose. Publisher Copyright: © 2022 British Pharmacological Society

PY - 2022/6

Y1 - 2022/6

N2 - Aims: 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 (5000 IU q8h, 10 000 IU q4h, or 25 000 IU q6h) for 6 ± 3 (mean ± standard deviation) days. Outcomes were activated partial thromboplastin time (APTT) before treatment (baseline) and highest-level during treatment (peak), and adverse events including bleeding. Exploratory efficacy outcomes were oxygenation, assessed by ratio of oxygen saturation to fraction of inspired oxygen (FiO2) and FiO2, and the World Health Organisation modified ordinal clinical scale. Results: There were 98 patients 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 <.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 =.17). Two patients had serious adverse events: bleeding gastric ulcer requiring transfusion and thigh haematoma; both were on therapeutic anticoagulation. Minor bleeding occurred in 16 patients, 13 of whom were on therapeutic anticoagulation. The oxygen saturation/FiO2 ratio and the FiO2 worsened before and improved after commencement of inhaled UFH (change in slope, P <.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.

AB - Aims: 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 (5000 IU q8h, 10 000 IU q4h, or 25 000 IU q6h) for 6 ± 3 (mean ± standard deviation) days. Outcomes were activated partial thromboplastin time (APTT) before treatment (baseline) and highest-level during treatment (peak), and adverse events including bleeding. Exploratory efficacy outcomes were oxygenation, assessed by ratio of oxygen saturation to fraction of inspired oxygen (FiO2) and FiO2, and the World Health Organisation modified ordinal clinical scale. Results: There were 98 patients 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 <.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 =.17). Two patients had serious adverse events: bleeding gastric ulcer requiring transfusion and thigh haematoma; both were on therapeutic anticoagulation. Minor bleeding occurred in 16 patients, 13 of whom were on therapeutic anticoagulation. The oxygen saturation/FiO2 ratio and the FiO2 worsened before and improved after commencement of inhaled UFH (change in slope, P <.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.

UR - http://www.scopus.com/inward/record.url?scp=85122888935&partnerID=8YFLogxK

U2 - 10.1111/bcp.15212

DO - 10.1111/bcp.15212

M3 - Article

AN - SCOPUS:85122888935

SN - 0306-5251

VL - 88

SP - 2802

EP - 2813

JO - British Journal of Clinical Pharmacology

JF - British Journal of Clinical Pharmacology

IS - 6

ER -