Use of novel antithrombotic agents for COVID-19: Systematic summary of ongoing randomized controlled trials.
COVID-19
RCT
anti-inflammatory
antithrombotic
antiviral
Journal
Journal of thrombosis and haemostasis : JTH
ISSN: 1538-7836
Titre abrégé: J Thromb Haemost
Pays: England
ID NLM: 101170508
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
received:
25
06
2021
accepted:
16
09
2021
pubmed:
20
9
2021
medline:
24
11
2021
entrez:
19
9
2021
Statut:
ppublish
Résumé
Coronavirus disease 2019 (COVID-19) is associated with macro- and micro-thromboses, which are triggered by endothelial cell activation, coagulopathy, and uncontrolled inflammatory response. Conventional antithrombotic agents are under assessment in dozens of randomized controlled trials (RCTs) in patients with COVID-19, with preliminary results not demonstrating benefit in several studies. Given the possibility that more novel agents with antithrombotic effects may have a potential utility for management of patients with COVID-19, we assessed ongoing RCTs including these agents with their potential mechanism of action in this population. We searched clinicaltrials.gov and the World Health Organization International Clinical Trials Registry Platform to identify RCTs of novel antithrombotic agents in patients with COVID-19. Based on a systematic literature search, 27 RCTs with 10 novel antithrombotic agents (including nafamostat, dociparstat, rNAPc2, and defibrotide) were identified. The results from these trials have not been disseminated yet. The studied drugs in the ongoing or completed RCTs include agents affecting the coagulation cascade, drugs affecting endothelial activation, and mixed acting agents. Their postulated antithrombotic mechanisms of action and their potential impact on patient management are summarized. Some novel antithrombotic agents have pleiotropic anti-inflammatory and antiviral effects, which may help reduce the viral load or fibrosis, and improve oxygenation. Results from ongoing RCTs will elucidate their actual role in the management of patients with COVID-19.
Sections du résumé
BACKGROUND
Coronavirus disease 2019 (COVID-19) is associated with macro- and micro-thromboses, which are triggered by endothelial cell activation, coagulopathy, and uncontrolled inflammatory response. Conventional antithrombotic agents are under assessment in dozens of randomized controlled trials (RCTs) in patients with COVID-19, with preliminary results not demonstrating benefit in several studies.
OBJECTIVES
Given the possibility that more novel agents with antithrombotic effects may have a potential utility for management of patients with COVID-19, we assessed ongoing RCTs including these agents with their potential mechanism of action in this population.
METHODS
We searched clinicaltrials.gov and the World Health Organization International Clinical Trials Registry Platform to identify RCTs of novel antithrombotic agents in patients with COVID-19.
RESULTS
Based on a systematic literature search, 27 RCTs with 10 novel antithrombotic agents (including nafamostat, dociparstat, rNAPc2, and defibrotide) were identified. The results from these trials have not been disseminated yet. The studied drugs in the ongoing or completed RCTs include agents affecting the coagulation cascade, drugs affecting endothelial activation, and mixed acting agents. Their postulated antithrombotic mechanisms of action and their potential impact on patient management are summarized.
CONCLUSION
Some novel antithrombotic agents have pleiotropic anti-inflammatory and antiviral effects, which may help reduce the viral load or fibrosis, and improve oxygenation. Results from ongoing RCTs will elucidate their actual role in the management of patients with COVID-19.
Identifiants
pubmed: 34538017
doi: 10.1111/jth.15533
pmc: PMC8646701
pii: S1538-7836(22)00554-2
doi:
Substances chimiques
Antiviral Agents
0
Fibrinolytic Agents
0
Types de publication
Journal Article
Systematic Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
3080-3089Informations de copyright
© 2021 International Society on Thrombosis and Haemostasis.
Références
Br J Haematol. 2021 Apr;193(1):43-51
pubmed: 33538335
J Thromb Haemost. 2004 Jan;2(1):65-70
pubmed: 14717968
Inflamm Regen. 2016 Jun 3;36:11
pubmed: 29259684
J Thromb Haemost. 2020 Nov;18(11):3113-3115
pubmed: 32945111
J Thromb Haemost. 2020 Nov;18(11):2812-2822
pubmed: 32762081
J Thromb Haemost. 2021 Sep;19(9):2225-2234
pubmed: 34236768
EClinicalMedicine. 2020 Nov;28:100590
pubmed: 33173853
J Am Coll Cardiol. 2021 Apr 20;77(15):1903-1921
pubmed: 33741176
JAMA. 2021 Apr 27;325(16):1620-1630
pubmed: 33734299
Lancet. 2021 Jun 12;397(10291):2253-2263
pubmed: 34097856
Cell. 2020 Apr 16;181(2):271-280.e8
pubmed: 32142651
Blood Coagul Fibrinolysis. 2009 Dec;20(8):627-34
pubmed: 19809307
Mol Med Rep. 2018 Jan;17(1):1717-1723
pubmed: 29138863
J Thromb Haemost. 2021 Apr;19(4):1038-1048
pubmed: 33534149
Br J Haematol. 2020 Jun;189(6):e227-e230
pubmed: 32369610
Eur Heart J. 2020 Jul 1;41(32):3058-3068
pubmed: 32656565
Am J Physiol Lung Cell Mol Physiol. 2020 Jun 1;318(6):L1237-L1238
pubmed: 32464083
Explore (NY). 2020 Nov - Dec;16(6):354-356
pubmed: 32229082
Eur Heart J. 2020 Sep 1;41(32):3038-3044
pubmed: 32882706
Int J Hematol. 2021 Mar;113(3):330-336
pubmed: 33471294
N Engl J Med. 2021 Aug 26;385(9):777-789
pubmed: 34351722
Circulation. 2021 Feb 23;143(8):865-868
pubmed: 33405941
J Am Coll Cardiol. 2020 Jun 16;75(23):2950-2973
pubmed: 32311448
J Thromb Haemost. 2020 Nov;18(11):3106-3108
pubmed: 32692894
ACS Infect Dis. 2020 Sep 11;6(9):2304-2318
pubmed: 32687696
J Clin Med. 2020 Jun 30;9(7):
pubmed: 32629976
Thromb Haemost. 2022 Jan;122(1):131-141
pubmed: 33865239