Table 3.

Combined treatment therapies with the use of NO-related compounds in clinical trials. SOC—standard of care.

Mode of Action	Combined Treatment	Effect
Free radical scavenger	Edaravone + Hyperbaric oxygen + Heparin (pilot trial)	-reduction of neurological symptoms (NIHSS)	[229]
	Edaravone + t-PA (pilot trial)	-early recanalization -higher percent of remarkable recovery (≥8-point reduction on NIHSS)	[230]
	Edaravone + t-PA (multicenter, prospective, randomized and open-label trial)	-no effect on the rate of early recanalization, symptomatic intracerebral hemorrhage or favorable outcome after tPA therapy	[231]
NMDA antagonist, VGSC and VGCC blocker, inhibitor of NO synthesis	Lubeluzole + t-PA (feasibility, safety and efficacy trial—uncompleted)	-study was terminated after Lubeluzole’s phase III trial showed no overall improvement	[232]
Statin	Simvastatin + t-PA (phase IV, prospective, randomized, double-blind, placebo-controlled trial)	-higher proportion of patients undergo major neurological recovery (post hoc analysis)	[233]
Typical antipsychotic + First-generation antihistamine	Chlorpromazine + Promethazine + SOC (pilot trial)	-no effect on neurological symptoms (NIHSS, mRS)	[234]