ImportanceCerebral vasospasm largely contributes to a devastating outcome after aneurysmal subarachnoid hemorrhage (aSAH), with limited therapeutic options.ObjectiveTo investigate the safety and efficacy of localized nicardipine release implants positioned around the basal cerebral vasculature at risk for developing proximal vasospasm after aSAH.Design, Setting, and ParticipantsThis 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.InterventionDuring 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).Main Outcome and MeasuresThe 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.ResultsOf 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 (P = .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%]; P = .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 (P = .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 (P = .27). The adverse event rate did not differ between groups.Conclusions and RelevanceThese 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.Trial RegistrationClinicalTrials.gov Identifier: NCT04269408

中文翻译：

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局部尼卡地平释放植入物预防动脉瘤性蛛网膜下腔出血后血管痉挛


重要性脑血管痉挛在很大程度上导致了动脉瘤性蛛网膜下腔出血 （aSAH） 后的破坏性结果，治疗选择有限。目的探讨定位尼卡地平释放植入物位于基底脑血管系统周围且有发生近端血管痉挛风险的 aSAH.Design、环境和参与者这项为期 52 周的单盲随机临床试验于 2020 年 4 月 5 日至 2023 年 1 月 23 日在德国和奥地利的 6 个学术神经血管中心进行。由于需要显微外科动脉瘤修复的前循环动脉瘤破裂而患有世界神经外科医师联合会 3 级或 4 级 aSAH 的连续患者参加了研究。干预在动脉瘤修复期间，患者以 1：1 的比例随机接受术中 10 个植入物，每个种植体 4 mg 尼卡地平加标准护理（种植体组）或单独动脉瘤修复加标准护理（对照组）。主要结局和测量主要终点是通过数字减影血管造影确定动脉瘤破裂后第 7 天至第 9 天之间中度至重度脑血管造影血管痉挛 （aVS） 的发生率。结果41 例患者中，20 例被随机分配到对照组 （平均 [SD] 年龄，54.9 [9.1] 岁;17 例女性 [85%]），21 例被随机分配到植入组 （平均 [SD] 年龄，53.6 [11.9] 岁;14 例女性 [67%]）。主要疗效分析共纳入 39 例患者。在对照组中，19 名患者中有 11 名 （58%） 发生中度或重度 aVS，而植入组 20 名患者中有 4 名 （20%） 发生中度或重度 aVS （P = .02）。 与对照组 （19 名患者中有 11 名 [58%] 相比，种植体组 （20 名患者中有 2 名 [10%]）对血管痉挛挽救治疗的临床需求较低;P = .002）。在动脉瘤破裂后第 13 天至第 15 天之间，对照组 19 例患者中有 6 例 （32%） 出现新脑梗死，种植体组 20 例患者中有 2 例 （10%） 出现新脑梗死 （P = .13）。在 52 周时，对照组 18 例患者中有 12 例 （67%） 和种植体组 19 例患者中有 16 例 （84%） 预后良好 （P = .27）。不良事件发生率在组间没有差异。结论和相关性这些发现表明，在显微外科动脉瘤修复过程中放置尼卡地平释放植入物可以安全有效地预防 aSAH 后中度至重度 aVS。可能需要进行 3 期临床试验，以调查尼卡地平植入物对临床结果的影响。试验注册临床试验。gov 标识符： NCT04269408