EDAS Revascularization for Symptomatic Intracranial Atherosclerotic Steno-Occlusive Disease (ERSIAS) Phase-II Trial

Abstract

Background: 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 collaterals from the extracranial circulation into cerebral hypoperfused areas. We present the results of a phase-II trial of EDAS in patients with ICAD failing medical management. Methods: ERSIAS was a prospective objective performance criterion (OPC) trial of EDAS plus intensive medical management (IMM) in patients with symptomatic ICAD despite optimized medical management, and poor angiographic collaterals. The primary endpoint was any stroke or death within 30 days postsurgery or stroke in the territory of the qualifying artery beyond 30 days. The primary analysis compared event rates through one year with the OPC of 10·1%, based on a 10% reduction from the 20·1% rate in the IMM arm of SAMMPRIS trial. The event rates through two years were compared with propensity-score-matched (PSM) medically treated patients from the SAMPPRIS and COSS trials. Secondary endpoints included functional neurological outcome and angiographic neovascularization. Findings: Fifty-two patients underwent EDAS-plus-IMM. The median age was 52 years (IQR=38·3-65·8), and 32 were females (61·5%). The primary endpoint rate at one year was 9·6%, lower than the OPC of 10·1% (p=0·07), meeting the p<0·10 threshold for nonfutility and advancement to phase-III. In the sensitivity analysis, the primary endpoint event rate at two years was lower than in PSM control patients, 9·6 % vs. 21·2% (p<0·07). Overall, 86% of EDAS-plus-IMM patients were functionally independent at last follow-up, and 89% demonstrated neovascularization. There were two (3·8%) surgical complications (wound dehiscence) and no intracranial hemorrhages. Interpretation: ERSIAS phase-II provides evidence of safety and strong signals of the efficacy of EDAS-plus-IMM, supporting testing of the technique in a randomized controlled clinical trial. Trial Registration: NCT01819597. Funding Statement: Research reported in this publication was supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (NIH), under award no. K23NS079477. Declaration of Interests: None. Ethics Approval Statement: Protocol ID:IRB#12-000439 UCLA IRB Initial Approval Date: 7/19/2012 Committee: Medical IRB 3