Clinical Trial: Surgical Indirect Revascularization For Symptomatic Intracranial Arterial Stenosis

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: EDAS (Surgical) Revascularization for Symptomatic Intracranial Arterial Stenosis

Brief Summary:

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 Summary: 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 invest
Sponsor: Cedars-Sinai Medical Center

Current Primary Outcome:

• Stroke or death after enrollment [ Time Frame: 30 days ]
  First primary study endpoint is stroke or death within 30 days after enrollment. Ischemic stroke is defined as a new focal neurological deficit of sudden onset, lasting at least 24 hours and not associated with CT or MRI findings of hemorrhage. Symptomatic cerebral hemorrhage is defined as parenchymal, subarachnoid or intraventricular bleeding detected in any imaging modality that is associated with new neurological deficits. Hemorrhage would only contribute to the primary endpoint if it occurs within 30 days after surgery.
• Stroke or death in the territory of qualifying artery [ Time Frame: 1 year ]
  The primary study endpoint is the composite of (1) any stroke or death within 30 days after enrollment, or (2) any ischemic stroke or death attributable to ischemia in the territory of the qualifying artery at one year. Ischemic stroke is defined as a new focal neurological deficit of sudden onset, lasting at least 24 hours and not associated with CT or MRI findings of hemorrhage.

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Any stroke or death [ Time Frame: 2 years ]
  Ischemic stroke is defined as a new focal neurological deficit of sudden onset, lasting at least 24 hours and not associated with CT or MRI findings of hemorrhage.
• Myocardial infarction [ Time Frame: 2 years ]
• Major non-stroke hemorrhage [ Time Frame: 2 years ]
  Systemic hemorrhage, subdural or epidural hemorrhages
• Functional outcome [ Time Frame: 2 years ]
  Functional outcome at the end of follow-up measured by the modified Rankin scale and Barthel Index
• Cognitive outcome [ Time Frame: 2 years ]
  Cognitive outcome at the end of follow-up measured by the Montreal Cognitive Assessment
• Improved collaterals [ Time Frame: 1 year ]
  Increase by at least one grade on the ASITN/SIR Angiographic Collateral Flow scale at one year.
• Asymptomatic cerebral hemorrhage [ Time Frame: 1 year ]
  Asymptomatic cerebral hemorrhage, defined as parenchymal or intraventricular bleeding detected in any imaging modality that is not associated with neurological deficits.

Original Secondary Outcome: Same as current

Information By: Cedars-Sinai Medical Center

Dates:
Date Received: March 24, 2013
Date Started: March 2013
Date Completion: February 2018
Last Updated: September 8, 2016
Last Verified: May 2016