Abstract 113: Novel Tissue Factor Inhibition For Thromboprophylaxis In COVID-19: Primary Results Of The ASPEN-COVID-19 Phase 2b Randomized Trial

Abstract

Background: Tissue factor contributes to thrombo-inflammation in viral infection and may be a target in COVID-19. Recombinant nematode anticoagulant protein c2 (rNAPc2), a tissue factor inhibitor with anticoagulant, anti-inflammatory, and antiviral properties, has not been studied in COVID-19. Methods: In Phase 2b of ASPEN-COVID-19 (NCT04655586), an open-label blinded endpoint study, COVID-19 inpatients with elevated D-dimer are randomized 1:1:2 to higher or lower dose rNAPc2 given subcutaneously up to 5 days or local standard of care heparin. Primary efficacy and safety endpoints are D-dimer change (to Day 8 or discharge if earlier) and ISTH major bleeding. Recovery time is an exploratory outcome. Results: 160 patients were randomized at 24 sites in 3 countries. The average age was 56 years, 43% were female, 19% were Hispanic, and 21% were black. Baseline comorbidities included hypertension (51%), diabetes (35%), and smoking (35%); 11% were critically ill. On average, randomization occurred 10 days after COVID-19 symptom onset, and qualifying D-dimers were elevated 3.7-fold above the upper limit of normal. Median recovery time was 6 days (aggregate distribution shown in Figure). Enrollment has completed, database lock is anticipated Q1 2022, and final results will be ready for presentation at Vascular Discovery. Conclusion: ASPEN tests the hypothesis that compared to heparin, rNAPc2 reduces D-dimer in COVID-19. Results may help to provide a novel therapy for thromboprophylaxis in virus-related coagulopathies.

TF-FVIIa PAR2-β-Arrestin Signaling Sustains Organ Dysfunction in Coxsackievirus B3 Infection of Mice

“…9 More recently, NAPc2 was also evaluated in COVID19 and showed anticoagulant efficacy without apparent interference with antiviral immunity. 69…”

Tissue Factor and COVID-19 Associated Thrombosis

“…The ASPEN-COVID-19 trial (Assessing Safety, Hospitalization and Efficacy of rNAPc2 in COVID-19) compared the effect of 8 days of treatment with recombinant NAPc2 to heparin (low molecular weight or unfractionated) on the activation of coagulation in patients with COVID-19. 38 Recombinant NAPc2 reduced plasma TF activity by 20.3%. However, it should be noted that measurement of TF in plasma is inferior to measurement of TF in isolated EVs, 37 and this low level of reduction may not accurately reflect the anticoagulant activity of rNAPc2.…”