Localized Nicardipine Release Implants for Prevention of Vasospasm After Aneurysmal Subarachnoid Hemorrhage: A Randomized Clinical Trial.

IF 20.4 1区 医学 Q1 CLINICAL NEUROLOGY
Lars Wessels, Stefan Wolf, Tiziana Adage, Jörg Breitenbach, Claudius Thomé, Johannes Kerschbaumer, Martin Bendszus, Matthias Gmeiner, Andreas Gruber, Dorothee Mielke, Veit Rohde, Maria Wostrack, Bernard Meyer, Jens Gempt, Gerhard Bavinzski, Dorian Hirschmann, Peter Vajkoczy, Nils Hecht
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引用次数: 0

Abstract

Importance: Cerebral vasospasm largely contributes to a devastating outcome after aneurysmal subarachnoid hemorrhage (aSAH), with limited therapeutic options.

Objective: 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.

Intervention: 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).

Main outcome and measures: 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.

Results: 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.

Conclusions and relevance: 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.

Trial registration: ClinicalTrials.gov Identifier: NCT04269408.

预防动脉瘤性蛛网膜下腔出血后血管痉挛的局部尼卡地平释放植入物:随机临床试验
重要性:动脉瘤性蛛网膜下腔出血(aSAH)后,脑血管痉挛在很大程度上导致了破坏性后果,但治疗方案却很有限:目的:研究在动脉瘤性蛛网膜下腔出血(ASAH)后有发生近端血管痉挛风险的基底脑血管周围植入尼卡地平释放型局部植入物的安全性和有效性:这项单掩蔽随机临床试验于 2020 年 4 月 5 日至 2023 年 1 月 23 日在德国和奥地利的 6 家神经血管学术中心进行,随访 52 周。世界神经外科医师联合会3级或4级前循环动脉瘤破裂导致的aSAH、需要进行显微外科动脉瘤修补术的连续患者参与了该试验:在动脉瘤修补术中,患者按1:1随机分配到术中接受10个植入物,每个4毫克尼卡地平加标准治疗(植入物组)或单纯动脉瘤修补术加标准治疗(对照组):主要终点是动脉瘤破裂后第7天至第9天数字减影血管造影确定的中度至重度脑血管痉挛(aVS)的发生率:在 41 名患者中,20 人被随机分配到对照组(平均 [SD] 年龄为 54.9 [9.1] 岁;17 名女性 [85%]),21 人被随机分配到植入组(平均 [SD] 年龄为 53.6 [11.9] 岁;14 名女性 [67%])。共有 39 名患者被纳入主要疗效分析。对照组 19 位患者中有 11 位(58%)出现中度或重度 aVS,而植入组 20 位患者中有 4 位(20%)出现中度或重度 aVS(P = .02)。与对照组(19 名患者中有 11 名[58%];P = .002)相比,植入组(20 名患者中有 2 名[10%])对血管痉挛抢救治疗的临床需求更低,这与上述结果不谋而合。动脉瘤破裂后第 13-15 天,对照组 19 位患者中有 6 位(32%)出现新的脑梗塞,植入组 20 位患者中有 2 位(10%)出现新的脑梗塞(P = .13)。52 周时,对照组 18 名患者中有 12 名(67%)和植入组 19 名患者中有 16 名(84%)获得了良好的治疗效果(P = .27)。两组的不良事件发生率没有差异:这些研究结果表明,在显微外科动脉瘤修补术中植入尼卡地平释放植入物可安全有效地预防中度至重度腹主动脉瓣狭窄。可能有必要进行第 3 期临床试验,研究尼卡地平植入物对临床结果的影响:试验注册:ClinicalTrials.gov Identifier:NCT04269408.
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来源期刊
JAMA neurology
JAMA neurology CLINICAL NEUROLOGY-
CiteScore
41.90
自引率
1.70%
发文量
250
期刊介绍: JAMA Neurology is an international peer-reviewed journal for physicians caring for people with neurologic disorders and those interested in the structure and function of the normal and diseased nervous system. The Archives of Neurology & Psychiatry began publication in 1919 and, in 1959, became 2 separate journals: Archives of Neurology and Archives of General Psychiatry. In 2013, their names changed to JAMA Neurology and JAMA Psychiatry, respectively. JAMA Neurology is a member of the JAMA Network, a consortium of peer-reviewed, general medical and specialty publications.
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