A randomized, open-label, adaptive, proof-of-concept clinical trial of modulation of host thromboinflammatory response i
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A randomized, open-label, adaptive, proofof-concept clinical trial of modulation of host thromboinflammatory response in patients with COVID-19: the DAWn-Antico study T. Vanassche1,2* , M. M. Engelen1,2, Q. Van Thillo3, J. Wauters4, J. Gunst5, C. Wouters6,7, C. Vandenbriele1,2, S. Rex2,8, L. Liesenborghs1,9, A. Wilmer4, P. Meersseman4, G. Van den Berghe5, D. Dauwe5, G. Verbeke10, M. Thomeer11,12, T. Fivez12,13, D. Mesotten12,13, D. Ruttens11, L. Heytens14, I. Dapper15, S. Tuyls16, B. De Tavernier15, P. Verhamme1,2 and DAWn consortium members
Abstract Background: The peak of the global COVID-19 pandemic has not yet been reached, and many countries face the prospect of a second wave of infections before effective vaccinations will be available. After an initial phase of viral replication, some patients develop a second illness phase in which the host thrombotic and inflammatory responses seem to drive complications. Severe COVID-19 disease is linked to high mortality, hyperinflammation, and a remarkably high incidence of thrombotic events. We hypothesize a crucial pathophysiological role for the contact pathway of coagulation and the kallikrein-bradykinin pathway. Therefore, drugs that modulate this excessive thromboinflammatory response should be investigated in severe COVID-19. Methods: In this adaptive, open-label multicenter randomized clinical trial, we compare low molecular weight heparins at 50 IU anti-Xa/kg twice daily—or 75 IU anti-Xa twice daily for intensive care (ICU) patients—in combination with aprotinin to standard thromboprophylaxis in hospitalized COVID-19 patients. In the case of hyperinflammation, the interleukin-1 receptor antagonist anakinra will be added on top of the drugs in the interventional arm. In a pilot phase, the effect of the intervention on thrombotic markers (D-dimer) will be assessed. In the full trial, the primary outcome is defined as the effect of the interventional drugs on clinical status as defined by the WHO ordinal scale for clinical improvement. (Continued on next page)
* Correspondence: [email protected] 1 Center for Molecular and Vascular Biology, KU Leuven Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium 2 Department of Cardiovascular Sciences, University Hospitals Leuven, Leuven, Belgium Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by
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