{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T19:17:34Z","timestamp":1773861454103,"version":"3.50.1"},"reference-count":30,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2013,3,12]],"date-time":"2013-03-12T00:00:00Z","timestamp":1363046400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["International Journal of Stroke"],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:sec><jats:title>Rationale<\/jats:title><jats:p> Epidemiological studies suggest that elevated homocysteine is linked to stroke and heart disease. However, the results of lowering homocysteine levels in reducing the risk of stroke recurrence are controversial. <\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p> The study aims to evaluate whether homocysteine-lowering therapy with folic acid and vitamins B<jats:sub>6<\/jats:sub> and B<jats:sub>12<\/jats:sub> reduces recurrent stroke events and other combined incidence of recurrent vascular events and vascular death in ischemic stroke patients of low folate regions. <\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p> This is a multicenter, randomized, double-blinded, placebo-controlled trial. Patients ( n = 8000, \u03b1 = 0\u00b705, \u03b2 = 0\u00b710) within one-month of ischemic stroke (large-artery atherosclerosis or small-vessel occlusion) or hypertensive intracerebral haemorrhage with plasma homocysteine level \u2a7e15 \u03bcmol\/l will be enrolled. Eligible patients will be randomized by a web-based, random allocation system to receive multivitamins (folic acid 0\u00b78 mg, vitamin B<jats:sub>6<\/jats:sub>10 mg, and vitamin B12 500 \u03bcg) or matching placebo daily with a median follow-up of three-years. <\/jats:p><\/jats:sec><jats:sec><jats:title>Study Outcomes<\/jats:title><jats:p> Patients will be evaluated at six monthly intervals. The primary outcome event is the composite event \u2018stroke, myocardial infarction, or death from any vascular cause\u2019, whichever occurs first. Secondary outcome measures include nonvascular death, transient ischemic attack, depression, dementia, unstable angina, revascularization procedures of the coronary, and cerebral and peripheral circulations. <\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p> This is the first multicenter randomized trial of secondary prevention for ischemic stroke in a Chinese population with a higher homocysteine level but without folate food fortification. <\/jats:p><\/jats:sec>","DOI":"10.1111\/ijs.12017","type":"journal-article","created":{"date-parts":[[2013,3,14]],"date-time":"2013-03-14T00:58:30Z","timestamp":1363222710000},"page":"264-268","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":12,"title":["The China Stroke Secondary Prevention Trial (CSSPT) Protocol: A Double-Blinded, Randomized, Controlled Trial of Combined Folic Acid and B Vitamins for Secondary Prevention of Stroke"],"prefix":"10.1177","volume":"10","author":[{"given":"Xuedong","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Neurology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junliang","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhirong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, School of Military Preventive Medicine, Fourth Military Medical University, Xi'an, Shaanxi, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, 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