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Title: Modulation of thromboinflammation in hospitalized COVID-19 patients with aprotinin, low molecular weight heparin, and anakinra: The DAWn-Antico study
Authors: Engelen, Matthias M.
Van Thillo, Quentin
Betrains, Albrecht
Gyselinck, Iwein
Martens, Caroline P.
Spalart, Valerie
Ockerman, Anna
Devooght, Caroline
Wauters, Joost
Gunst, Jan
Wouters, Carine
Vandenbriele, Christophe
Rex, Steffen
Liesenborghs, Laurens
Wilmer, Alexander
Meersseman, Philippe
Van den Berghe , Greet
Dauwe , Dieter
Belmans, Ann
THOMEER, Michiel 
Fivez, Tom
Heytens, Luc
Dapper, Ilse
Tuyls, Sebastiaan
De Tavernier, Brecht
Verhamme, Peter
Vanassche, Thomas
Issue Date: 2022
Publisher: WILEY
Source: Research and Practice in Thrombosis and Haemostasis, 6 (7) (Art N° e12826)
Abstract: Background Thromboinflammation plays a central role in severe COVID-19. The kallikrein pathway activates both inflammatory pathways and contact-mediated coagulation. We investigated if modulation of the thromboinflammatory response improves outcomes in hospitalized COVID-19 patients. Methods In this multicenter open-label randomized clinical trial (EudraCT 2020-001739-28), patients hospitalized with COVID-19 were 1:2 randomized to receive standard of care (SOC) or SOC plus study intervention. The intervention consisted of aprotinin (2,000,000 IE IV four times daily) combined with low molecular weight heparin (LMWH; SC 50 IU/kg twice daily on the ward, 75 IU/kg twice daily in intensive care). Additionally, patients with predefined hyperinflammation received the interleukin-1 receptor antagonist anakinra (100 mg IV four times daily). The primary outcome was time to a sustained 2-point improvement on the 7-point World Health Organization ordinal scale for clinical status, or discharge. Findings Between 24 June 2020 and 1 February 2021, 105 patients were randomized, and 102 patients were included in the full analysis set (intervention N = 67 vs. SOC N = 35). Twenty-five patients from the intervention group (37%) received anakinra. The intervention did not affect the primary outcome (HR 0.77 [CI 0.50-1.19], p = 0.24) or mortality (intervention n = 3 [4.6%] vs. SOC n = 2 [5.7%], HR 0.82 [CI 0.14-4.94], p = 0.83). There was one treatment-related adverse event in the intervention group (hematuria, 1.49%). There was one thrombotic event in the intervention group (1.49%) and one in the SOC group (2.86%), but no major bleeding. Conclusions In hospitalized COVID-19 patients, modulation of thromboinflammation with high-dose aprotinin and LMWH with or without anakinra did not improve outcome in patients with moderate to severe COVID-19.
Notes: Engelen, MM (corresponding author), Herestr 49 Box 911-ON1, B-3000 Leuven, Belgium.
Keywords: anakinra;aprotinin;COVID-19;heparin;inflammation;low-molecular-weight;thrombosis
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e-ISSN: 2475-0379
DOI: 10.1002/rth2.12826
ISI #: 000875879800001
Rights: 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH). This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made
Category: A1
Type: Journal Contribution
Appears in Collections:Research publications

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