Department of Neurosurgery, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Center for Stroke Research Berlin, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
JAMA Neurol. 2024 Oct 1;81(10):1060-1065. doi: 10.1001/jamaneurol.2024.2564.
Cerebral vasospasm largely contributes to a devastating outcome after aneurysmal subarachnoid hemorrhage (aSAH), with limited therapeutic options.
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.
DESIGN, SETTING, AND PARTICIPANTS: 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.
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).
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.
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 (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.
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.
ClinicalTrials.gov Identifier: NCT04269408.
蛛网膜下腔出血（aSAH）后血管痉挛在很大程度上导致了毁灭性的结果，目前治疗选择有限。
研究局部尼卡地平释放植入物在 aSAH 后基底脑血管发生近端血管痉挛风险部位的安全性和疗效。
设计、地点和参与者：这是一项单盲随机临床试验，随访 52 周，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。连续纳入因前循环破裂性动脉瘤需要显微手术动脉瘤修复的世界神经外科学会 3 级或 4 级 aSAH 患者。
在动脉瘤修复过程中，患者被随机分为 1:1 组，在术中接受 10 个 4mg 尼卡地平的植入物，加标准护理（植入物组）或仅接受动脉瘤修复加标准护理（对照组）。
主要终点是通过数字减影血管造影术确定的动脉瘤破裂后第 7 至 9 天中度至重度脑血管造影性血管痉挛（aVS）的发生率。
41 例患者中，20 例被随机分配至对照组（平均[标准差]年龄 54.9[9.1]岁；17 例女性[85%]），21 例至植入物组（平均[标准差]年龄 53.6[11.9]岁；14 例女性[67%]）。共有 39 例患者纳入主要疗效分析。对照组 19 例患者中有 11 例（58%）发生中度或重度 aVS，而植入物组 20 例患者中有 4 例（20%）（P=0.02）。在植入物组中，临床需要血管痉挛挽救治疗的比例较低（20 例患者中有 2 例[10%]），而对照组中则较高（19 例患者中有 11 例[58%]；P=0.002）。在动脉瘤破裂后第 13 至 15 天，对照组 19 例患者中有 6 例（32%）出现新的脑梗死，而植入物组 20 例患者中有 2 例（10%）（P=0.13）。在 52 周时，对照组 18 例患者中有 12 例（67%）和植入物组 19 例患者中有 16 例（84%）的结局良好（P=0.27）。两组的不良事件发生率无差异。
这些发现表明，在显微手术动脉瘤修复过程中放置尼卡地平释放植入物可安全有效地预防 aSAH 后中度至重度 aVS。可能需要进行一项关于尼卡地平植入物对临床结局影响的 3 期临床试验。
ClinicalTrials.gov 标识符：NCT04269408。
