Table 1.

Summary of the potential treatment approaches, their mechanisms of action, and ongoing clinical development.

Thrombus component target	Molecule	Mechanism of action	Ongoing clinical trials
Fibrin network	Tenecteplase	Genetically modified form of human tPA	Several randomized phase 3 trials are ongoing to confirm the efficacy of tenecteplase compared to alteplase (NCT03854500; NCT04915729)
	TAFI inhibitor	Inhibitor of fibrinolysis inhibitor	Two ongoing phase 1–2 clinical trials are assessing the safety of a TAFI inhibitor infusion (NCT03198715; NCT02586233)
	PAI-1 inhibitor	Inhibitor of fibrinolysis inhibitor	None
vWF multimers	N-acetylcysteine (NAC)	Reducing intrachain disulfide bonds in large polymeric proteins	The NAC for thrombolysis in acute stroke (NAC-S) trial (ClinicalTrials.gov: NCT04920448) is an ongoing phase 2 randomized study assessing the safety of NAC combined with IV tPA in AIS setting
	rhADAMTS-13	Specific VWF-cleaving metalloprotease	None
Platelet aggregates	Cangrelor	Platelet P2Y12 receptor inhibitor	A phase 3 randomized trial is currently assessing the benefit of cangrelor infusion in imaging-selected AIS patients eligible for EVT (ClinicalTrials.gov: NCT04667078)
	Glenzocimab	Antibody to platelet glycoprotein VI	Phase 2 randomized trial is currently assessing the safety of glenzocimab infusion on top of IV tPA in AIS patients (ClinicalTrials.gov: NCT03803007)
Extracellular DNA	Dornase Alfa	Recombinant human form of DNAse 1	A pilot phase 2 trial is assessing the safety and efficacy of IV DNase 1 in AIS patients receiving IV tPA and eligible for EVT (NETs-TARGET study, ClinicalTrials.gov: NCT04785066)