Surgical Indirect Revascularization For Symptomatic Intracranial Arterial Stenosis

NCT01819597 | Completed Results DMC

• 1 other identifier: K23NS079477-01A1
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

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.

Conditions

Intracranial Arterial Stenosis; Intracranial Atherosclerosis; Ischemic Stroke; Cerebral Angiogenesis

Keywords

Intracranial Arterial Stenosis; Atherosclerosis; Stroke; EDAS; Angiogenesis

Outcome Measures

Primary Outcomes (1)

• Stroke or Death in the Territory of Qualifying Artery

  The primary study endpoint is the number of participants with any stroke or death within 30 days after enrollment, or 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.

  1 year

Secondary Outcomes (6)

• Myocardial Infarction

  30 days

• Major Non-stroke Hemorrhage

  2 years

• Functional Outcome

  2 years

• Cognitive Outcome

  2 years

• Improved Collaterals

  1 year

Study Arms (1)

EDAS surgery

OTHER

EDAS surgery is an established form of indirect revascularization. The study arm in this study will receive EDAS surgery

Procedure: Encephaloduroarteriosynangiosis (EDAS)

Interventions

Encephaloduroarteriosynangiosis (EDAS) PROCEDURE

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.

Also known as: Indirect revascularization, Indirect bypass, EC-IC revascularization, EC-IC indirect bypass, EC-IC indirect revascularization

EDAS surgery

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• TIA or non-severe stroke within 30 days of enrollment attributed to 70% to 99% stenosis\* of a major intracranial artery (carotid artery or MCA)
• \*May be diagnosed by TCD, MRA, or CTA to qualify, but must be confirmed by catheter angiography as per usual clinical practice.
• Modified Rankin scale score of ≤3
• Target area of stenosis in an intracranial artery that has a normal diameter of 2.00 mm to 4.50 mm
• Target area of stenosis is ≤14 mm in length
• Age ≥30 years and ≤80 years
• \* Patients 30 to 49 years of age are required to meet at least 1 additional criteria (i-vi) provided below to qualify for the study. This additional requirement is to increase the likelihood that the symptomatic intracranial stenosis in patients 30 to 49 years is atherosclerotic: i. Insulin-dependent diabetes for at least 15 years ii. At least 2 of the following atherosclerotic risk factors: hypertension (BP ≥ 140/90 mm Hg or on antihypertensive therapy); dyslipidemia (LDL ≥130 mg/dL or HDL ≤40 mg/dL or fasting triglycerides ≥150 mg/dL or on lipid lowering therapy); smoking; non-insulin-dependent diabetes or insulin-dependent diabetes of \<15 years duration; family history of any of the following: myocardial infarction, coronary artery bypass, coronary angioplasty or stenting, stroke, carotid endarterectomy or stenting, and peripheral vascular surgery in parent or sibling who was \< 55 years of age for men or \< 65 for women at the time of the event.
• iii. History of any of the following: myocardial infarction, coronary artery bypass, coronary angioplasty or stenting, carotid endarterectomy or stenting, or peripheral vascular surgery for atherosclerotic disease iv. Any stenosis of an extracranial carotid or vertebral artery, another intracranial artery, subclavian artery, coronary artery, iliac or femoral artery, other lower or upper extremity artery, mesenteric artery, or renal artery that was documented by noninvasive vascular imaging or catheter angiography and is considered atherosclerotic v. Aortic arch atheroma documented by noninvasive vascular imaging or catheter angiography vi. Any aortic aneurysm documented by noninvasive vascular imaging or catheter angiography that is considered atherosclerotic
• Negative pregnancy test in a female who has had any menses in the last 18 months
• Patient is willing and able to return for all follow-up visits required by the protocol.
• Patient is available by phone.
• Patient understands the purpose and requirements of the study, can make him/herself understood, and has provided informed consent.
• Demonstration of poor or no collateral flow in the territory of the qualifying stenotic vessel (ASITN/SIR Collateral Flow Grades 0-2) and hypoperfusion of the vascular territory in MRI.

You may not qualify if:

• Tandem extracranial or intracranial stenosis (70-99%) or occlusion that is proximal or distal to the target intracranial lesion
• Bilateral intracranial vertebral artery stenosis of 70% to 99% and uncertainty about which artery is symptomatic (e.g., if patient has pontine, midbrain, or temporal occipital symptoms)
• Stenting, angioplasty, or endarterectomy of an extracranial (carotid or vertebral artery) or intracranial artery within 30 days before the expected enrollment date
• Previous treatment of target lesion with a stent, angioplasty, or other mechanical device, or plan to perform staged angioplasty followed by stenting of target lesion
• Plan to perform concomitant angioplasty or stenting of an extracranial vessel tandem to an intracranial stenosis
• Presence of intraluminal thrombus proximal to or at the target lesion
• Any aneurysm proximal to or distal to the stenotic intracranial artery
• Intracranial tumor (including meningioma) or any intracranial vascular malformation
• Computed tomographic or angiographic evidence of severe calcification at target lesion
• Thrombolytic therapy within 24 hours before enrollment
• Progressive neurologic signs within 24 hours before enrollment
• Brain infarct within previous 30 days of enrollment that is of sufficient size (\> 5 cm) to be at risk of hemorrhagic conversion during or after surgery
• Any hemorrhagic infarct within 14 days before enrollment
• Any hemorrhagic infarct within 15 to 30 days that is associated with mass effect
• Any history of a primary intracerebral (parenchymal) hemorrhage

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Related Publications (5)

• Dusick JR, Liebeskind DS, Saver JL, Martin NA, Gonzalez NR. Indirect revascularization for nonmoyamoya intracranial arterial stenoses: clinical and angiographic outcomes. J Neurosurg. 2012 Jul;117(1):94-102. doi: 10.3171/2012.4.JNS111103. Epub 2012 May 4.

  PMID: 22559848 BACKGROUND

• Gonzalez NR, Liebeskind DS, Dusick JR, Mayor F, Saver J. Intracranial arterial stenoses: current viewpoints, novel approaches, and surgical perspectives. Neurosurg Rev. 2013 Apr;36(2):175-84; discussion 184-5. doi: 10.1007/s10143-012-0432-z. Epub 2012 Oct 25.

  PMID: 23097149 BACKGROUND

• Dusick JR, Gonzalez NR, Martin NA. Clinical and angiographic outcomes from indirect revascularization surgery for Moyamoya disease in adults and children: a review of 63 procedures. Neurosurgery. 2011 Jan;68(1):34-43; discussion 43. doi: 10.1227/NEU.0b013e3181fc5ec2.

  PMID: 21150753 BACKGROUND

• Gonzalez NR, Jiang H, Lyden P, Song S, Schlick K, Dumitrascu O, Quintero-Consuegra MD, Toscano JF, Liebeskind DS, Restrepo L, Rao N, Hinman J, Alexander MJ, Schievink W, Piantadosi S, Saver JL. Encephaloduroarteriosynangiosis (EDAS) revascularization for symptomatic intracranial atherosclerotic steno-occlusive (ERSIAS) Phase-II objective performance criterion trial. Int J Stroke. 2021 Aug;16(6):701-709. doi: 10.1177/1747493020967256. Epub 2020 Oct 29.

  PMID: 33115382 DERIVED

• Laiwalla AN, Ooi YC, Van De Wiele B, Ziv K, Brown A, Liou R, Saver JL, Gonzalez NR. Rigorous anaesthesia management protocol for patients with intracranial arterial stenosis: a prospective controlled-cohort study. BMJ Open. 2016 Jan 19;6(1):e009727. doi: 10.1136/bmjopen-2015-009727.

  PMID: 26787251 DERIVED

MeSH Terms

Conditions

Intracranial Arteriosclerosis; Ischemic Stroke; Atherosclerosis; Stroke

Condition Hierarchy (Ancestors)

Intracranial Arterial Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Limitations and Caveats

None. Trial was completed as planned

Results Point of Contact

• Title: Nestor Gonzalez, MD. Professor of Neurosurgery
• Organization: Cedars-Sinai Medical Center

nestor.gonzalez@cshs.org

310 423 0783

Study Officials

• Nestor R Gonzalez, MD, MSCR

  Cedars Sinai Neurosurgery

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurosurgery

Model Details: EDAS surgery for Intracranial atherosclerosis. Non-futility design

Study Record Dates

• First Submitted: March 24, 2013
• First Posted: March 27, 2013
• Study Start: March 1, 2013
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2018
• Last Updated: May 10, 2019
• Results First Posted: May 10, 2019

Record last verified: 2019-05

Locations

US (1)