{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T21:31:54Z","timestamp":1793136714189,"version":"4.5.0"},"reference-count":34,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,1]]},"abstract":"\nOBJECTIVE<\/jats:title>\nIschemic complications account for significant patient morbidity following aneurysmal subarachnoid hemorrhage (aSAH). The Prevention and Treatment of Vasospasm with Clazosentan (REACT) study was designed to assess the safety and efficacy of clazosentan, an endothelin receptor antagonist, in preventing clinical deterioration due to delayed cerebral ischemia (DCI) in patients with aSAH.<\/jats:p>\n<\/jats:sec>\n\nMETHODS<\/jats:title>\nREACT was a prospective, multicenter, randomized, double-blind, phase 3 study. Eligible patients had aSAH secured by surgical clipping or endovascular coiling, and had presented with thick and diffuse clot on admission CT scan. Patients were randomized (1:1 ratio) to 15 mg\/hour intravenous clazosentan or placebo within 96 hours of the aSAH for up to 14 days, in addition to standard of care treatment including oral or intravenous nimodipine. The primary efficacy endpoint was the occurrence of clinical deterioration due to DCI up to 14 days after initiation of the study drug. The main secondary endpoint was the occurrence of clinically relevant cerebral infarction at day 16 after study drug initiation. Other secondary endpoints included clinical outcome assessed on the modified Rankin Scale (mRS) and the Glasgow Outcome Scale\u2013Extended (GOSE) at week 12 post-aSAH. Imaging and clinical endpoints were centrally adjudicated.<\/jats:p>\n<\/jats:sec>\n\nRESULTS<\/jats:title>\nA total of 409 patients were randomized between February 2019 and May 2022 across 74 international sites. Three patients did not start study treatment and were not included in the analysis set. The occurrence of clinical deterioration due to DCI was 15.8% (32\/202 patients) in the clazosentan group and 17.2% (35\/204 patients) in the placebo group, and the difference was not statistically significant (relative risk reduction [RRR] 7.2%, 95% CI \u201342.6% to 39.6%, p = 0.734). A nonsignificant RRR of 34.1% (95% CI \u201321.3% to 64.2%, p = 0.177) was observed in clinically relevant cerebral infarcts treated with clazosentan (7.4%, 15\/202) versus placebo (11.3%, 23\/204). Rescue therapy was less frequently needed for patients treated with clazosentan compared to placebo (10.4%, 21\/202 vs 18.1%, 37\/204; RRR 42.6%, 95% CI 5.4%\u201365.2%). A nonsignificant relative risk increase of 25.4% (95% CI \u201310.7% to 76.0%, p = 0.198) was reported in the risk of poor GOSE and mRS scores with clazosentan (24.8%, 50\/202) versus placebo (20.1%, 41\/204) at week 12 post-aSAH. Treatment-emergent adverse events were similar to those reported previously.<\/jats:p>\n<\/jats:sec>\n\nCONCLUSIONS<\/jats:title>\nClazosentan administered for up to 14 days at 15 mg\/hour had no significant effect on the occurrence of clinical deterioration due to DCI.<\/jats:p>\nClinical trial registration no.: NCT03585270 (ClinicalTrials.gov<\/jats:ext-link>)<\/jats:p>\nEU clinical trial registration no.: 2018-000241-39 (clinicaltrialsregister.eu<\/jats:ext-link>)<\/jats:p>\n<\/jats:sec>","DOI":"10.3171\/2024.4.jns232191","type":"journal-article","created":{"date-parts":[[2024,8,10]],"date-time":"2024-08-10T01:30:40Z","timestamp":1723253440000},"page":"1-12","source":"Crossref","is-referenced-by-count":46,"title":["REACT: a randomized trial to assess the efficacy and safety of clazosentan for preventing clinical deterioration due to delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage"],"prefix":"10.3171","author":[{"given":"Stephan A.","family":"Mayer","sequence":"first","affiliation":[{"name":"Neurocritical Care and Emergency Neurological Services, Westchester Medical Center Health Network, Valhalla, New York;"},{"name":"Department of Neurology and Neurosurgery, New York Medical College, New York, New York;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Bruder","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Critical Care, CHU Timone, APHM, Aix-Marseille University, Marseille, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Citerio","sequence":"additional","affiliation":[{"name":"School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Defreyne","sequence":"additional","affiliation":[{"name":"Department of Interventional Radiology and Neuroradiology, Ghent University, Ghent, Belgium;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecile","family":"Dubois","sequence":"additional","affiliation":[{"name":"Biometry, Idorsia Pharmaceuticals Ltd., Allschwil, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajiv","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Radiology, Division of Neuroradiology, Massachusetts General Hospital, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall","family":"Higashida","sequence":"additional","affiliation":[{"name":"Department of Radiology, Division of Neurointerventional Radiology, University of California, San Francisco Medical Center, San Francisco, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelina","family":"Marr","sequence":"additional","affiliation":[{"name":"Global Clinical Development, Idorsia Pharmaceuticals Ltd., Allschwil, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanh N.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Neurosurgery, and Radiology, Boston University Chobanian & Avedisian School of Medicine, Boston Medical Center, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Roux","sequence":"additional","affiliation":[{"name":"Global Clinical Development, Idorsia Pharmaceuticals Ltd., Allschwil, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Smr\u010dka","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University Hospital Brno, Czechia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramon Torn\u00e9","family":"Torn\u00e9","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Hospital Clinic of Barcelona, Spain; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. 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