Encephaloduroarteriosynangiosis (EDAS) revascularization for symptomatic intracranial atherosclerotic steno-occlusive (ERSIAS) Phase-II objective performance criterion 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 extra-cranial collaterals to intracranial vessels. We present the results of a phase-II trial of EDAS in intracranial atherosclerotic disease patients. Aims To evaluate the feasibility, safety, and preliminary efficacy of EDAS in intracranial atherosclerotic disease patients. Methods 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). Results 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. Conclusion 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. Clinical Trial Registration URL: https://www.clinicaltrials.gov.NCT01819597 .

Encephaloduroarteriosynangiosis Operative Technique and Intraoperative Anesthesia Management: Treatment From Both Sides of the Curtain

“…Based on our experience, we believe there are 3 main factors that mitigate the risk of perioperative stroke in patients with ICAD undergoing EDAS: standardized hemodynamic and ventilatory parameters that are strictly controlled during the anesthetic period, consistent and rigorous IMM in the perioperative period, and decreased risk of surgical complications, given the simplicity of the EDAS procedure compared with direct bypass. This hypothesis is further supported by the recent ERSIAS PC trial that showed a 7.7% risk of perioperative stroke after EDAS in patients with ICAD, 7 a more favorable rate than those demonstrated in EC-IC (12%) 22 and COSS 23 (15%) direct bypass trials.…”

“…Although the EDAS technique has been described several times in the literature, no reports have evaluated the multidisciplinary approach to improve operative outcomes and the effects of maintaining strict medical management in patients at high risk of recurrent stroke. As the role of EDAS potentially expands to treat conditions such as ICAD, 3,5,7,21 it is necessary to identify the detailed nuances and variables that can be controlled to ensure good outcomes.…”

“…In association with stroke neurologists and neuroanesthesiologists, we developed protocols focused on continuous maintenance of intensive medical management (IMM) of stroke risk factors and strict intraoperative control of hemodynamic parameters, which improved EDAS outcomes in challenging patients with intracranial atherosclerotic disease (ICAD) and hemodynamic failure. 6,7,9,10 Specifically, we have generated and implemented medical management and anesthesia-specific guidelines to reduce cerebral perfusion pressure (CPP) variability during surgery. 9,10 To adapt to the medical and physiologic demands during surgery, we modified the surgical technique with standardized methods that reduce undesirable surgical events during the operation.…”

Trends in Literature on Cerebral Bypass Surgery: A Systematic Review

“…The findings of the still ongoing Chinese Middle Cerebral Artery Occlusion Surgery Study [23] are expected to provide further insights into the role of bypass surgery for steno-occlusive disease. Furthermore, the recently published American Encephaloduroarteriosynangiosis Revascularization for Symptomatic Intracranial Arterial Stenosis phase II trial provided the evidence of safety and strong signals of efficacy of indirect bypass in addition to the best medical management [24], supporting advancement to a consecutive phase IIb/III trial.…”

Commentary: Modern Appraisal of Patency and Complications in Cerebral Bypass Surgery: A Single Institution Experience

“…6,15 However, for steno-occlusive disease, recent evidence has raised the possibility that indirect bypass may provide good protection against future stroke. 16,17 Over time, it is likely that at least for STA-middle cerebral artery bypass for moyamoya disease, a standard benchmark for perioperative complications may be established similar to that for carotid endarterectomy or carotid stenting. In this context, it is essential that the right patients are selected for surgery, and the right procedures are offered.…”