Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.
Int J Stroke. 2021 Aug;16(6):701-709. doi: 10.1177/1747493020967256. Epub 2020 Oct 29.
Intracranial atherosclerotic disease (ICAD) is one of the most challenging stroke etiologies, with frequent recurrences despite optimized medical management. Encephaloduroarteriosynangiosis (EDAS) is an indirect revascularization method that produces extra-cranial collaterals to intracranial vessels. We present the results of a phase-II trial of EDAS in intracranial atherosclerotic disease patients.
To evaluate the feasibility, safety, and preliminary efficacy of EDAS in intracranial atherosclerotic disease patients.
ERSIAS was a prospective objective-performance-criterion trial of EDAS plus intensive medical management (IMM) in intracranial atherosclerotic disease (ICAD) patients failing medical treatment. Primary endpoint was any stroke/death within 30-days post-surgery or stroke in the territory of the qualifying artery beyond 30 days. The primary analysis compared event rates through one year with an objective-performance-criterion based on a 10% reduction from the 20% rate in the intensive medical management arm of the stenting versus aggressive medical management for preventing recurrent stroke in intracranial stenosis trial (SAMMPRIS) in patients with poor collaterals. Event rates through two years were compared with propensity-score-matched (PSM) medically treated patients from SAMMPRIS and the carotid occlusion surgery study (COSS).
During a median follow-up of 24.5 months, 5 (9.6%) of 52 patients had a primary endpoint event. The primary endpoint rate at one year met the threshold for nonfutility and advancement to phase III (<10%). In the sensitivity analysis, primary endpoint event rate at two years was lower than in PSM controls, 9.6% versus 21.2% (p < 0.07). Overall, 86% of EDAS-plus-intensive medical management patients were functionally independent at last follow-up and 89% demonstrated neovascularization. There were two (3.8%) surgical complications and no intracranial hemorrhages.
ERSIAS phase II provides evidence of safety and strong signals of efficacy of EDAS-plus-intensive medical management, supporting advancement to a seamless phase-IIb/III trial.
颅内动脉粥样硬化性疾病（ICAD）是最具挑战性的中风病因之一，尽管进行了优化的药物治疗，但仍频繁复发。硬脑膜血管融通术（EDAS）是一种间接的血管再通方法，可使颅外血管与颅内血管形成侧支循环。我们报告了 EDAS 在颅内动脉粥样硬化性疾病患者中的 II 期试验结果。
评估 EDAS 在颅内动脉粥样硬化性疾病患者中的可行性、安全性和初步疗效。
ERSIAS 是一项前瞻性的 EDAS 加强化药物治疗（IMM）治疗颅内动脉粥样硬化性疾病（ICAD）患者的目标-性能-标准试验，这些患者经药物治疗后无效。主要终点是术后 30 天内任何中风/死亡或 30 天后 qualifying 动脉区域内的中风。主要分析通过一年的时间比较事件发生率，该发生率基于一项基于 10%降低的客观性能标准，即支架治疗颅内狭窄预防复发性中风试验（SAMMPRIS）中强化药物治疗组 20%的比率，以及狭窄性颈动脉闭塞手术研究（COSS）中的药物治疗患者。通过倾向性评分匹配（PSM）与 SAMMPRIS 和 COSS 的药物治疗患者比较两年的事件发生率。
在中位随访 24.5 个月期间，52 例患者中有 5 例（9.6%）发生主要终点事件。一年时的主要终点事件发生率达到非无效性和推进到 III 期的阈值（<10%）。在敏感性分析中，两年时的主要终点事件发生率低于 PSM 对照组，分别为 9.6%和 21.2%（p<0.07）。总的来说，86%的 EDAS 加强化药物治疗患者在最后一次随访时具有独立的功能，89%的患者显示出新生血管化。有 2 例（3.8%）手术并发症，无颅内出血。
ERSIAS II 期提供了 EDAS 加强化药物治疗的安全性证据和疗效的强烈信号，支持无缝的 IIb/III 期试验推进。
网址：https://www.clinicaltrials.gov. NCT01819597。
