Surgical Indirect Revascularization For Symptomatic Intracranial Arterial Stenosis "ERSIAS"

Recruiting

Phase 2 Results N/A

Trial Description

Stroke due to intracranial arterial atherosclerosis is a significant medical problem, carrying one of the highest rates of recurrent stroke despite best medical therapy, with annual recurrence rates as elevated as 25% in high risk groups.
The goal of this investigation is to advance a promising surgical treatment for symptomatic atherosclerotic intracranial stenosis - encephaloduroarteriosynangiosis (EDAS). The investigation will test in a phase II futility trial the potential of EDAS for further development before proceeding with the design of a definitive clinical trial of EDAS Revascularization in patients with Symptomatic Intracranial Arterial Stenosis (ERSIAS).
The investigation is a 4-year futility trial to test the hypothesis that EDAS revascularization combined with aggressive medical therapy warrants further evaluation in a subsequent pivotal trial as an alternative to aggressive medical management alone for preventing the primary endpoint of stroke or death in patients with symptomatic intracranial arterial stenosis (Specific Aim 1). During the investigation the time course of collateralogenesis and perfusion improvement following EDAS will also be evaluated (Specific Aim 2.

Detailed Description

Intracranial arterial atherosclerosis is a significant medical problem, with elevated rates of recurrent stroke despite medical therapy, with annual recurrence rates for ischemic stroke reported in the SAMMPRIS Trial as high as 12.2% in the intensive medical therapy arm. The incidence of recurrence stroke can be even higher in some high-risk groups, as high as 25% in African-Americans and females. The ultimate goal of this project is to advance a promising surgical treatment for symptomatic atherosclerotic intracranial stenosis - encephaloduroarteriosynangiosis (EDAS). Compared with direct revascularization operations (bypass), EDAS has the advantages of being less technically demanding, avoiding temporary occlusion of cerebral vessels, and allowing gradual development of collateral circulation where the brain demands it, deterring early hyperperfusion and hemorrhage. There has been no systematic trial exploring the use of EDAS in cases of symptomatic, non-moyamoya intracranial arterial stenosis. Based on preliminary positive results, the investigators propose the long-term objective of demonstrating that EDAS improves the outcome in patients with symptomatic intracranial stenosis compared with aggressive medical therapy. This will require future phase III clinical trials. The present proposal has the purpose of testing in a phase II futility-design trial the potential of EDAS for further development before proceeding with the design of a definitive clinical trial of EDAS Revascularization in patients with Symptomatic Intracranial Arterial Stenosis (ERSIAS). The present project will be 4-year futility-design trial to determine if EDAS revascularization combined with aggressive medical therapy warrants further evaluation in a subsequent pivotal trial as an alternative to aggressive medical management alone for preventing the primary endpoint of stroke or death at two years in patients with symptomatic intracranial arterial stenosis (Specific Aim 1). During the investigation the investigators will systematically evaluate the time course of collateralogenesis and perfusion improvement following EDAS by using quantitative and semiquantitative perfusion MRI studies (Specific Aim 2). The new knowledge generated by this study on understanding the role of collateral circulation in stroke pathophysiology, patient selection, and use of non-invasive imaging will be useful not only for EDAS evaluation but potentially next generation stents and future novel medical therapies, such as use of angiogenic growth factors and/or endothelial stem cells.

Conditions

Interventions

  • Encephaloduroarteriosynangiosis (EDAS) Procedure
    Other Names: Indirect revascularization; Indirect bypass; EC-IC revascularization; EC-IC indirect bypass; EC-IC indirect revascularization
    Intervention Desc: The operation is a form of indirect revascularization or EC-IC bypass, performed under general endotracheal anesthesia, with intraoperative electroencephalographic monitoring. The surgery consists in the dissection and relocation of the superficial temporal artery (STA) and middle meningeal artery (MMA) branches, which are separated from their surrounding tissues under microscopic visualization and re-routed through a craniotomy to be placed intracranially in close proximity to the branches of the middle cerebral artery (MCA). The MCA branches are dissected in the arachnoid space and the STA and MMA are kept in position with microsutures to the arachnoid or MMA dural cuffs, maintaining close contact between the EC and MCA branches.
    ARM 1: Kind: Experimental
    Label: EDAS surgery
    Description: EDAS surgery is an established form of indirect revascularization. The study arm in this study will receive EDAS surgery

Trial Design

  • Masking: Open Label
  • Purpose: Treatment
  • Endpoint: Safety/Efficacy Study
  • Intervention: Single Group Assignment

Outcomes

Type Measure Time Frame Safety Issue
Primary Stroke or death after enrollment 30 days Yes
Primary Stroke or death in the territory of qualifying artery 1 year Yes
Secondary Any stroke or death 2 years Yes
Secondary Myocardial infarction 2 years Yes
Secondary Major non-stroke hemorrhage 2 years Yes
Secondary Functional outcome 2 years No
Secondary Cognitive outcome 2 years No
Secondary Improved collaterals 1 year No
Secondary Asymptomatic cerebral hemorrhage 1 year Yes

Sponsors