{"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":1793136714209,"version":"4.5.0"},"reference-count":17,"publisher":"American Medical Association (AMA)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2024,10,1]]},"abstract":"\n Importance<\/jats:title>\n Cerebral vasospasm largely contributes to a devastating outcome after aneurysmal subarachnoid hemorrhage (aSAH), with limited therapeutic options.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To investigate the safety and efficacy of localized nicardipine release implants positioned around the basal cerebral vasculature at risk for developing proximal vasospasm after aSAH.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This single-masked randomized clinical trial with a 52-week follow-up was performed between April 5, 2020, and January 23, 2023, at 6 academic neurovascular centers in Germany and Austria. Consecutive patients with World Federation of Neurological Surgeons grade 3 or 4 aSAH due to a ruptured anterior circulation aneurysm requiring microsurgical aneurysm repair participated.<\/jats:p>\n <\/jats:sec>\n \n Intervention<\/jats:title>\n During aneurysm repair, patients were randomized 1:1 to intraoperatively receive 10 implants at 4 mg of nicardipine each plus standard of care (implant group) or aneurysm repair alone plus standard of care (control group).<\/jats:p>\n <\/jats:sec>\n \n Main Outcome and Measures<\/jats:title>\n The primary end point was the incidence of moderate to severe cerebral angiographic vasospasm (aVS) between days 7 and 9 after aneurysm rupture as determined by digital subtraction angiography.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Of 41 patients, 20 were randomized to the control group (mean [SD] age, 54.9 [9.1] years; 17 female [85%]) and 21 to the implant group (mean [SD] age, 53.6 [11.9] years; 14 female [67%]). A total of 39 patients were included in the primary efficacy analysis. In the control group, 11 of 19 patients (58%) developed moderate or severe aVS compared with 4 of 20 patients (20%) in the implant group (\n P<\/jats:italic>\n \u2009=\u2009.02). This outcome was paralleled by a lower clinical need for vasospasm rescue therapy in the implant group (2 of 20 patients [10%]) compared with the control group (11 of 19 patients [58%];\n P<\/jats:italic>\n \u2009=\u2009.002). Between days 13 and 15 after aneurysm rupture, new cerebral infarcts were noted in 6 of 19 patients (32%) in the control group and in 2 of 20 patients (10%) in the implant group (\n P<\/jats:italic>\n \u2009=\u2009.13). At 52 weeks, favorable outcomes were noted in 12 of 18 patients (67%) in the control group and 16 of 19 patients (84%) in the implant group (\n P<\/jats:italic>\n \u2009=\u2009.27). The adverse event rate did not differ between groups.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n These findings show that placing nicardipine release implants during microsurgical aneurysm repair can provide safe and effective prevention of moderate to severe aVS after aSAH. A phase 3 clinical trial to investigate the effect of nicardipine implants on clinical outcome may be warranted.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT04269408<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaneurol.2024.2564","type":"journal-article","created":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T11:00:42Z","timestamp":1724065242000},"page":"1060","source":"Crossref","is-referenced-by-count":18,"title":["Localized Nicardipine Release Implants for Prevention of Vasospasm After Aneurysmal Subarachnoid Hemorrhage"],"prefix":"10.1001","volume":"81","author":[{"given":"Lars","family":"Wessels","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany"},{"name":"Center for Stroke Research Berlin, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Wolf","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany"},{"name":"Center for Stroke Research Berlin, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Adage","sequence":"additional","affiliation":[{"name":"Brain Implant Therapeutics (BIT) Pharma GmbH, Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Breitenbach","sequence":"additional","affiliation":[{"name":"Brain Implant Therapeutics (BIT) Pharma GmbH, Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudius","family":"Thom\u00e9","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Medizinische Universit\u00e4t Innsbruck, Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Kerschbaumer","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Medizinische Universit\u00e4t Innsbruck, Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Bendszus","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, Ruprecht-Karls Universit\u00e4t Heidelberg, Heidelberg, 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