Table 3.

Clinical trials of remote ischemic conditioning (RIC) targeting ischemic stroke

Name of study	Type of patients/pathology	size and phase of study	Primary outcomes	Secondary outcomes	RIC protocol*	Main results/observations	Status	Ref
RESIST	Acute ischemic stroke and intracerebral hemorrhage	intention of including 1000 patients	3 months modified Rankin Scale score	3 categories: clinical, neuroimaging and plasma biomarkers	5 cycles pre-hospital and in hospital	Not available	ongoing	[109]
RECAST	Acute ischemic stroke	pilot study with 26 patients	feasibility and tolerability	blood biomarkers and 90 day NIHSS score	4 cycles in the first 24 h after stroke onset	RIC decreased 90 day NIHSS score and increased plasma levels of HSP-27	completed	[110]
RECAST-2	Acute ischemic stroke	60 stroke patients phase IIb	feasibility and tolerability	blood biomarkers and 90 day NIHSS score	4 cycles in the first 24 h after stroke onset	no changes in NIHSS score but RIC decreased S100ß plasma concentration	completed	[111]
RECAST-3	Acute ischemic stroke	1300 stroke patients phase III	Death or dependency at day 90 (modified Rankin Scale)	At day 90: Cerebrovascular events; major adverse cardiac and cerebral events; acute kidney injury; COVID-19 status; disability; cognition; mood; frailty; quality of life; safety	4 doses of 4 cycles Dose 1 in the first 6 h after stroke onset; second dose 2 h after dose 1 and 2 doses at day 2	Multicenter clinical trial	ongoing	[112]
no name	Acute ischemic stroke	proof-of-concept study, 443 patients	penumbral salvage (assessed on multimodal magnetic resonance imaging)	infarct growth at 24 h and 1 month follow-up	4 cycles during the first 4 h (when transportation was too short less cycles were done)	mostly neutral, some indication that RIC reduces the risk of infarction after 1 month	completed	[113, 114]
RESCUE BRAIN	Carotid acute ischemic stroke	multicenter including 188 patients	Infarct volume at 24 h	NIHSS score at 24 h and at 90 days: activities of daily living, degree of disability, excellent outcome, successful recanalization	4 cycles up to 6 h after stroke onset	at 90 days no significant difference in mortality or symptomatic intracerebral hemorrhage	completed	[115, 116]
REPOST	Acute ischemic stroke	intention of including 200 acute ischemic stroke patients	Infarct size (MRI diffusion-weighted image) at the end of hospitalization	Modified Rankin Scale, NIHSS, quality of life, and cardiovascular and cerebrovascular morbidity and mortality	4 cycles twice daily during the hospitalization for a maximum of 4 days	Not available	ongoing	[117]
no name	Acute minor ischemic stroke or transient ischemic attack	165 patients, phase IIa	prevention of secondary stroke	not applicable	5 cycles on bilateral upper limbs twice a day for 90 days	RIC to be used and tested along with the antiplatelet strategy (aspirin and/or clopidogrel)	ongoing	[118]
no name	Acute ischemic stroke in patients treated with thrombectomy	pilot study with 20 patients treated with thrombectomy	safety, feasibility and assessment of any serious RIC-related adverse events	not applicable	4 cycles applied before and immediately after recanalization, and once a day for 7 days	no RIC-induced effect on intracranial pressure, cranial perfusion, mean arterial pressure or middle artery systolic flow velocity	completed	[119]
no name	Acute ischemic stroke in patients treated intravenous thrombolysis	pilot study with 49 patients treated with intravenous thrombolysis	safety	not applicable	4 cycles applied within 6-24 h of intravenous thrombolysis	No difference was found in: hemorrhagic transformation, clinical score, adverse events, blood pressure But RIC group presented lower levels of C reactive protein	completed	[120]