Pathway | Agent | Animal study outcomes | Clinical study outcomes | Recruiting COVID-19 trials | ||
Tissue factor | TFPI | Coagulation activation | Reduced [42, 107, 108] | Coagulation activation | Reduced [37, 109] | |
Inflammation | Reduced [36, 110, 111] No effect [108, 112] | Inflammation | Reduced [37] No effect [109] | |||
Bacterial clearance | Increased [110] | Mortality | Reduced [40]# No effect [37, 39, 41]¶,+ | |||
Risk of bleeding | Increased [37, 39]§ | |||||
Factor X | Rivaroxaban Apixabanƒ | Inflammation | Reduced [113] | NCT04416048 NCT04394377 NCT04351724 | ||
Alveolar leak | Reduced [113] | |||||
Thrombin | Anti-thrombin Dabigatranƒ Bivalirudinƒ | Coagulation activation | Reduced [46] | Mortality | No effect [45, 47] Reduced mortality in subgroup not receiving concomitant heparin [47] | |
Inflammation | Reduced [42, 46] | Risk of bleeding | Increased [47]§ | |||
Alveolar leak | Reduced [42, 46] | |||||
Bacterial clearance | Increased [46] | |||||
Heparin | Coagulation activation | Reduced [46] No effect [42] | Mortality | No effect [51–53, 79] | NCT04372589 NCT04401293 NCT04367831 NCT04345848 NCT04373707 NCT04366960 NCT04359277 NCT04397510 | |
Inflammation | No effect [42, 46] | |||||
Alveolar leak | No effect [42, 46] | |||||
Bacterial clearance | No effect [42, 46] | |||||
APC | rhAPC | Coagulation activation | Reduced [46, 60] | Coagulation activation | Reduced [63] | |
Inflammation | Reduced [61] No effect [60] | Lung injury score | Reduced [63] | |||
Alveolar leak | Reduced [61] | Mortality | Reduced [22] No effect [55, 65–67] | |||
Fibrosis | Reduced [61] | |||||
Bacterial clearance | No effect [61] | |||||
Fibrinogen | tPA uPA | Coagulation activation | No effect [74] | Mortality | Reduced [79] | NCT04356833 NCT04357730 |
Inflammation | Reduced [78] No effect [74, 76] | |||||
Alveolar leak | Reduced [76, 78] No effect [74] | |||||
Fibrinolysis | Increased [74, 78] | |||||
PAR-1 | Vorapaxar RWJ-58269 | Coagulation activation | Reduced [114] | |||
Inflammation | Reduced [94, 115] | |||||
Alveolar leak | Reduced [94, 115] | |||||
Bacterial clearance | No effect [94, 115] |
TFPI: tissue factor pathway inhibitor; APC: activated protein C; rhAPC: recombinant human APC; tPA: tissue-type plasminogen activator; uPA: urokinase-type plasminogen activator; PAR-1: proteinase-activated receptor-1. #: trend towards reduced mortality in TFPI-treated group of community-acquired pneumonia patients who had not received concomitant heparin and in whom the pathogen was identified [40]; ¶: trend towards reduced mortality in TFPI group not receiving concomitant heparin [39]; +: trend towards reduced mortality in TFPI group (trial not powered for effect on mortality) [37]; §: difference in risk of major bleeding was not significant in those who did not receive concomitant heparin [47]; ƒ: no relevant studies were identified using this anticoagulant.