Abstract Number: OC 13.5
Meeting: ISTH 2022 Congress
Background: Thromboinflammation in severe COVID-19 is associated with disease severity and inferior outcome. Evidence suggests that the kallikrein pathway potentially plays a vital role in COVID-19 associated thromboinflammation as it both activates downstream inflammatory pathways and contact-mediated coagulation.
Aims: To investigate whether modulation of this pronounced thromboinflammatory response can improve outcomes in hospitalized patients with severe COVID-19.
Methods: This multicenter randomized clinical trial was approved by the ethics committee and supported by the KU Leuven COVID-19 fund and Research Foundation Flanders (FWO). After informed consent, eligible patients were 1:2 randomized to receive standard of care (SOC) or SOC plus study intervention (figure 1). The intervention consisted of off-label – kallikrein-inhibiting – aprotinin combined with low molecular weight heparin (LMWH). Additionally, patients with predefined hyperinflammation were treated with the interleukin-1 receptor antagonist anakinra. The primary endpoint was time to sustain a 2-point improvement in the WHO ordinal scale for clinical status.
Results: Three hospitals in Belgium included 102 patients (35 SOC vs. 67 intervention). Twenty-five patients from the intervention group (37%) were treated with anakinra. Patients had elevated D-dimers (mean 1012.4 µg/L; SD 991.9 µg/L) and C-reactive protein (mean 81.4 mg/L; SD 59.6 mg/L) at admission confirming baseline activation of coagulation and inflammatory pathways. During hospitalization, 37% of patients were admitted to the ICU (29% SOC vs. 42% intervention), and 20% needed invasive ventilation (12% SOC vs. 25% intervention). The intervention did not affect the time to sustained clinical improvement or hospital discharge (figure 2), nor secondary clinical endpoints. Except for D-dimers at day 3, there was no significant C-reactive protein or D-dimer reductions. There were no differences in treatment-related adverse events.
Conclusion(s): In hospitalized COVID-19 patients, additional modulation of thromboinflammation with high-dose aprotinin and LMWH with or without anakinra was feasible and safe but did not improve clinical nor biochemical outcomes.
To cite this abstract in AMA style:Engelen M, Wauters J, Gunst J, Wouters C, Vandenbriele C, Rex S, Thomeer M, Fivez T, Mesotten D, Ruttens D, Heytens L, Verhamme P, Vanassche T. A Multicenter Randomized Clinical Trial of Modulation of Host Thromboinflammatory Response in Hospitalized Patients with COVID-19: The DAWn-Antico study [abstract]. https://abstracts.isth.org/abstract/a-multicenter-randomized-clinical-trial-of-modulation-of-host-thromboinflammatory-response-in-hospitalized-patients-with-covid-19-the-dawn-antico-study/. Accessed September 21, 2023.
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