{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T12:54:25Z","timestamp":1788526465504,"version":"build-2803163510"},"reference-count":21,"publisher":"S. Karger AG","issue":"1-2","license":[{"start":{"date-parts":[[2017,1,1]],"date-time":"2017-01-01T00:00:00Z","timestamp":1483228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2017,1,1]],"date-time":"2017-01-01T00:00:00Z","timestamp":1483228800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cerebrovasc Dis"],"published-print":{"date-parts":[[2017]]},"abstract":"<b><i>Background:<\/i><\/b> Clazosentan has been explored worldwide for the prophylaxis of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH). In a dose-finding trial (CONSCIOUS-1) conducted in Israel, Europe, and North America, clazosentan (1, 5, and 15 mg\/h) significantly reduced the incidence of cerebral vasospasm, but its efficacy in Japanese and Korean patients was unknown. We conducted a double-blind comparative study to evaluate the occurrence of cerebral vasospasm in Japanese and Korean patients with aSAH. <b><i>Methods:<\/i><\/b> The aim of this multicenter, double-blind, randomized, placebo-controlled, dose-finding phase 2 clinical trial, was to evaluate the efficacy, pharmacokinetics, and safety of clazosentan (5 and 10 mg\/h) against cerebral vasospasm after clipping surgery in Japanese and Korean patients with aSAH. Patients aged between 20 and 75 years were administered the study drug within 56 h after the aneurysm rupture and up to day 14 post-aSAH. The incidence of vasospasm, defined as an inner artery diameter reduction of major intracranial arteries \u226534% based on catheter angiography, was compared between each treatment group. Cerebral infarction due to vasospasm at 6 weeks and patients' outcome at 3 months was also compared. <b><i>Results:<\/i><\/b> Among 181 enrolled patients, 158 completed the study and were analyzed. The incidence of vasospasm up to day 14 after aSAH onset was 80.0% in the placebo group (95% CI 67.0-89.6), 38.5% in the 5 mg\/h clazosentan group (95% CI 25.3-53.0), and 35.3% in the 10 mg\/h clazosentan group (95% CI 22.4-49.9), indicating that the incidence of vasospasm was significantly reduced by clazosentan treatment (placebo vs. 5 mg\/h clazosentan, <i>p<\/i> < 0.0001; placebo vs. 10 mg\/h clazosentan, <i>p<\/i> < 0.0001). The occurrence of cerebral infarction due to vasospasm was 20.8% in the placebo group (95% CI 10.8-34.1), 3.8% in the 5 mg\/h clazosentan group (95% CI 0.5-13.2), and 4.2% in the 10 mg\/h clazosentan group (95% CI 0.5-14.3), indicating that clazosentan significantly reduced the occurrence of cerebral infarctions caused by vasospasm (placebo vs. 5 mg\/h clazosentan, <i>p<\/i> = 0.0151; placebo vs. 10 mg\/h clazosentan, <i>p<\/i> = 0.0165). The overall incidence of all-cause death and\/or vasospasm-related morbidity\/mortality was significantly reduced in the 10 mg\/h clazosentan group compared with the placebo group (<i>p<\/i> = 0.0003). <b><i>Conclusion:<\/i><\/b> These results suggest that clazosentan prevents cerebral vasospasm and subsequent cerebral infarction, and could thereby improve outcomes after performing a clipping surgery for aSAH in Japanese and Korean patients.<\/jats:p>","DOI":"10.1159\/000475824","type":"journal-article","created":{"date-parts":[[2017,5,2]],"date-time":"2017-05-02T21:01:59Z","timestamp":1493758919000},"page":"59-67","source":"Crossref","is-referenced-by-count":73,"title":["Preventive Effect of Clazosentan against Cerebral Vasospasm after Clipping Surgery for Aneurysmal Subarachnoid Hemorrhage in Japanese and Korean Patients"],"prefix":"10.1159","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0991-0516","authenticated-orcid":false,"given":"Miki","family":"Fujimura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Yang","family":"Joo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Soo","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motonori","family":"Hatta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinari","family":"Yokoyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3411-2900","authenticated-orcid":false,"given":"Teiji","family":"Tominaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2017,5,3]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1007\/s10143-006-0045-5"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1161\/STR.0b013e3182587839"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.25.4.904"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(94)90273-9"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1038\/332411a0"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.108.519942"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.111.648980"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-7091-1192-5_7"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2458-12-439"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1983.59.2.0223"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.106.477976"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1177\/0091270007307337"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.3171\/jns.2005.103.1.0009"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.109.547331"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.2176\/nmc.50.7"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1007\/s007010050260"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2013.246"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.7887\/jcns.24.232"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1586\/14779072.5.3.531"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-7091-1192-5_22"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.3171\/2013.3.JNS12683"}],"container-title":["Cerebrovascular Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/475824","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/475824","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/475824","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T16:23:36Z","timestamp":1745425416000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000475824"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017]]},"references-count":21,"journal-issue":{"issue":"1-2","published-online":{"date-parts":[[2017,7,28]]},"published-print":{"date-parts":[[2017,8,3]]}},"URL":"https:\/\/doi.org\/10.1159\/000475824","archive":["Portico"],"relation":{},"ISSN":["1015-9770","1421-9786"],"issn-type":[{"value":"1015-9770","type":"print"},{"value":"1421-9786","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017]]}}}