{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:01:16Z","timestamp":1790744476246,"version":"4.1.0"},"reference-count":16,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Remote ischemic conditioning (RIC) has emerged as a promising non-invasive strategy to protect the brain, with evidence suggesting its benefit in patients with carotid artery stenting (CAS). However, the long-term benefit and safety of chronic RIC in this population remain unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate whether chronic RIC reduces the incidence of major vascular events in high-risk patients with carotid artery stenosis who received CAS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>RICSICAS is a prospective, randomized, open-label, blinded endpoint evaluation (PROBE), single-center trial. We plan to enroll 450 high-risk patients with symptomatic carotid artery stenosis (Essen score \u2265 3) scheduled for CAS. Participants will be randomly assigned (1:1) to receive either standard medical therapy plus RIC or standard medical therapy alone. The RIC protocol involves bilateral upper-arm cuff inflation to 200 mmHg (5-min inflation\/5-min deflation, 5 cycles) performed 1\u20132 times daily, starting 3 days before CAS and continuing for 12 months post-procedure, thus constituting a combined peri-procedural and chronic RIC strategy. The primary efficacy endpoint is the composite of stroke, myocardial infarction, TIA, and vascular death within 12 months. Safety endpoints include any RIC-related adverse event (e.g., limb pain, petechiae, peripheral nerve injury), and any serious adverse event.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Sample Size<\/jats:title>\n                    <jats:p>Assuming a 12-month event rate of 20% in the control group and a 40% relative risk reduction with RIC, with 80% power and a two-sided \u03b1 of 0.05, 355 patients are required. Accounting for a 20% dropout rate\/loss-to-follow-up, as well as the consumption of the interim analysis, the total sample size is set as 450.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This trial will provide high-level evidence on the role of long-term RIC as an adjunctive therapy for high-risk patients with symptomatic carotid artery stenosis undergoing CAS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>Clinicaltrials.gov<\/jats:ext-link>\n                      , identifier: NCT07412249.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1915534","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:51:40Z","timestamp":1790743900000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Remote ischemic conditioning plus stenting for symptomatic carotid artery stenosis (RICSICAS): rationale and design"],"prefix":"10.3389","volume":"17","author":[{"given":"Jing","family":"Qiu","sequence":"first","affiliation":[{"name":"Department of Neurology, General Hospital of Northern Theater Command","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, General Hospital of Northern Theater Command","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Gang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurology, General Hospital of Northern Theater Command","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Qi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, General Hospital of Northern Theater Command","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, General Hospital of Northern Theater Command","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Sheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, General Hospital of Northern Theater Command","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1136\/svn-2021-001374","article-title":"China stroke statistics: an update on the 2019 report from the national center for healthcare quality management in neurological diseases, China national clinical research center for neurological diseases, the Chinese stroke association, national center for chronic and non-communicable disease control and prevention, Chinese center for disease control and prevention and institute for global neuroscience and stroke collaborations","volume":"7","author":"Wang","year":"2022","journal-title":"Stroke Vasc Neurol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1056\/NEJM199108153250701","article-title":"Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis","volume":"325","author":"North American Symptomatic Carotid Endarterectomy Trial","year":"1991","journal-title":"N Engl J Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1016\/S0140-6736(06)69122-8","article-title":"30 day results from the SPACE trial of stent-protected angioplasty versus carotid endarterectomy in symptomatic patients: a randomised non-inferiority trial","volume":"368","author":"SPACE Collaborative","year":"2006","journal-title":"Lancet"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1660","DOI":"10.1056\/NEJMoa061752","article-title":"Endarterectomy versus stenting in patients with symptomatic severe carotid stenosis","volume":"355","author":"Mas","year":"2006","journal-title":"N Engl J Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1016\/S0140-6736(10)60239-5","volume":"375","year":"2010","journal-title":"Lancet"},{"key":"B6","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1016\/S1474-4422(10)70057-0","article-title":"New ischaemic brain lesions on MRI after stenting or endarterectomy for symptomatic carotid stenosis: a substudy of the international carotid stenting study (ICSS)","volume":"9","author":"Bonati","year":"2010","journal-title":"Lancet Neurol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1056\/NEJMoa2508800","article-title":"Medical management and revascularization for asymptomatic carotid stenosis","volume":"394","author":"Brott","year":"2026","journal-title":"N Engl J Med"},{"key":"B8","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1161\/STROKEAHA.108.521419","article-title":"The essen stroke risk score predicts recurrent cardiovascular events: a validation within the reduction of atherothrombosis for continued health (REACH) registry","volume":"40","author":"Weimar","year":"2009","journal-title":"Stroke"},{"key":"B9","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1007\/s00270-014-1000-4","article-title":"Results of the prospective, multicenter, non-randomized, independently adjudicated ASTI trial: carotid artery stenting in high-risk patients","volume":"38","author":"Bosiers","year":"2015","journal-title":"Cardiovasc Intervent Radiol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1177\/17474930231191082","article-title":"Remote ischemic conditioning for stroke: a critical systematic review","volume":"19","author":"Keevil","year":"2024","journal-title":"Int J Stroke."},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2015.223","article-title":"Remote ischaemic conditioning-a new paradigm of self-protection in the brain","author":"Hess","year":"2015","journal-title":"Nat Rev Neurol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1001\/jama.2022.18829","article-title":"Effect of remote ischemic conditioning vs usual care on neurologic function in patients with acute moderate ischemic stroke: the RICAMIS randomized clinical trial","volume":"328","author":"Cui","year":"2022","journal-title":"JAMA"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1016\/S1474-4422(22)00335-0","article-title":"Chronic remote ischaemic conditioning in patients with symptomatic intracranial atherosclerotic stenosis (the RICA trial): a multicentre, randomised, double-blind sham-controlled trial in China","volume":"21","author":"Hou","year":"2022","journal-title":"Lancet Neurol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"101796","DOI":"10.1016\/j.xcrm.2024.101796","article-title":"Effect of remote ischemic preconditioning on cerebral circulation time in severe carotid artery stenosis: results from the RIC-CCT trial","volume":"5","author":"Liu","year":"2024","journal-title":"Cell Rep Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1325","DOI":"10.1161\/CIRCULATIONAHA.116.024807","article-title":"Safety and efficacy of remote ischemic preconditioning in patients with severe carotid artery stenosis before carotid artery stenting: a proof-of-concept, randomized controlled trial","volume":"135","author":"Zhao","year":"2017","journal-title":"Circulation."},{"key":"B16","doi-asserted-by":"publisher","first-page":"2251","DOI":"10.2147\/NDT.S433383","article-title":"The predictive value of essen and SPI-II on the risk of 5-year recurrence in Chinese patients with acute ischemic stroke","volume":"19","author":"Zhao","year":"2023","journal-title":"Neuropsychiatr Dis Treat."}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1915534\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:51:43Z","timestamp":1790743903000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1915534\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,30]]},"references-count":16,"alternative-id":["10.3389\/fneur.2026.1915534"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2026.1915534","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,30]]},"article-number":"1915534"}}