Open AccessModulation of thromboinflammation in hospitalized COVID‐19 patients with aprotinin, low molecular weight heparin, and anakinra: The DAWn‐Antico study
Author(s) -
Engelen Matthias M.,
Van Thillo Quentin,
Betrains Albrecht,
Gyselinck Iwein,
Martens Caroline P.,
Spalart Valérie,
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,
Mesotten Dieter,
Ruttens David,
Heytens Luc,
Dapper Ilse,
Tuyls Sebastiaan,
De Tavernier Brecht,
Verhamme Peter,
Vanassche Thomas
Publication year - 2022
Publication title -
research and practice in thrombosis and haemostasis
Language(s) - English
Resource type - Journals
ISSN - 2475-0379
DOI - 10.1002/rth2.12826
Subject(s) - anakinra , medicine , randomized controlled trial , adverse effect , clinical endpoint , disease
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.