Clinical trial NCT03179774: Endovascular Revascularization for Chronic Carotid Artery Occlusion Trial
Official title: Endovascular Revascularization for Chronic Carotid Artery Occlusion Trial (ERCAO Trial) Part 1: Prospective Clinical Registry Study Part 2: Prospective Randomized Control Trial Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Carotid Occlusion
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2017-06-07
Enrollment: 200
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Part 1: Clinical registry study (Optimal medical therapy group vs. Endovascular revascularization and optimal medical therapy) Part 2: Randomized control trial (Optimal medical therapy group vs. Endovascular revascularization and optimal medical therapy)
Primary purpose: TREATMENT

Brief summary: Revascularization for carotid artery occlusion (CAO) remained controversial, there is no prospective randomized control trial (RCT) regarding carotid artery stenting (CAS) in CAO patients. The investigators conduct a prospective study composed of clinical registry arm and RCT arm. The main purpose of the study is investigate neurocognitive function at 3 months and thereafter up to 12 months.

Detailed description: Carotid artery stenosis is an important cause of stroke. Carotid artery stenting (CAS) provides non-inferior clinical outcome comparing to carotid endarterectomy (CEA). However, revascularization for carotid artery occlusion (CAO) remained controversial, owing to failed extracranial-to-intracranial (EC-IC) artery bypass trials, anatomical hindrance for CEA, and technical limitation for CAS. In the past 10 years, the investigators devoted in endovascular therapy for CAO and published innovative and pilot study results regarding feasibility of CAS for CAO, neurocognitive function (NCF) improvement after successful CAS for CAO, and predictors for CAS success in CAO, all in high-ranking journals. Moreover, successful CAS for CAO would lead to lower mortality and stroke rate during long-term follow-up, according to the preliminary analysis from the investigators. However, there is no prospective randomized control trial (RCT) regarding CAS in CAO patients, and in fact, most of the CAS trials excluded CAO.

The investigators, with the largest volume and experience in CAO recanalization in the world, felt obliged and responsible to propose the following RCT to evaluate endovascular revascularization for chronic CAO.

The study composed of two parts. The first part composed of prospective clinical registry for CAO. The second part compose of a prospective superiority trial, rater blinded, with 1:1 randomization to evaluate the clinical efficacy of interventional therapy for CAO. Eligible candidates for CAO revealed by CT, ultrasonography, angiography, or magnetic resonance imaging (MRI), with abnormal brain perfusion demonstrated by CT perfusion study (CTP) or MRI, will be enrolled in to study. If the participants agreed for randomization, participants will be randomized into 2 groups: the optimal medical therapy (OMT) group and the endovascular revascularization plus optimal medical therapy (ER+OMT) group. The primary end-point of the trial is the NCF improvement at 3 months and thereafter up to 12 months. The secondary endpoint includes: cumulative incidence of death and stroke within 30 days after the procedure; death or ipsilateral stroke between 31 days and 1 year; major stroke, ischemic stroke, or hemorrhagic stroke within 30 days after the procedure; major stroke, ischemic stroke, or hemorrhagic stroke between 31 days and 1 year; cognitive function measured by CANTAB; change of cerebral perfusion measured by CTP; target vessel revascularization rate; technique success rate; procedure success rate; and major procedure complication.

Eligibility criteria: Part 1: Clinical registry study

Inclusion criteria for clinical registry study

* Patient age 20 years or older
* Abnormal cerebral perfusion by CTP or MRI
* No medical history of stroke or transient ischemic attack (TIA) ipsilateral to the carotid occlusion within 90 days of randomization
* Women must not be of childbearing potential or, if of childbearing potential, have a negative pregnancy test prior to randomization.

Exclusion Criteria for clinical registry study

* Patient has acute stroke within 90 days,
* Intolerance or allergic reaction to a study medication without a suitable management alternative.
* Patient is expected to have the ADP antagonist therapy interruption within 3 months after the procedure.
* GI hemorrhage within 1 month prior to enrollment that would preclude antiplatelet therapy
* Bleeding diathesis
* Intracranial hemorrhage within the past 12 months.
* Platelet count \<100,000/μl or history of heparin-induced thrombocytopenia.
* Other high-risk cardiac sources of emboli, including left ventricular aneurysm, severe cardiomyopathy, aortic or mitral mechanical heart valve, severe calcific aortic stenosis (valve area \< 1.0 cm2), endocarditis, moderate to severe mitral stenosis, left atrial thrombus, or any intracardiac mass, or known unrepaired patent foramen ovale (PFO) with prior paradoxical embolism.
* Any major surgery, major trauma, revascularization procedure within the past 1 month.
* Acute coronary syndrome within the past 1 month or acute coronary syndrome (ACS) that is not amenable to revascularization (patients should undergo planned coronary revascularization at least 30 days before randomization).
* Inability to understand and cooperate with study procedures or provide informed consent.
* Patients with \< 5 years life expectancy
* Concomitant vascular conditions precluding endovascular revascularization procedure;
* Previous ipsilateral carotid artery stenting
* Intracranial aneurysm or arteriovenous malformation;
* Educational level lower than elementary school;
* Aphasia or right-sided hemiparesis
* Marked depression.
* Severe dementia.

Part 2: Randomized control study

Inclusion Criteria for randomized control study

* Patient age 20 years or older
* Abnormal cerebral perfusion by CTP or MRI
* No medical history of stroke or TIA ipsilateral to the carotid occlusion within 90 days of randomization
* Patients must have a modified Rankin Scale (mRS) ≤2 at the time of informed consent.
* Women must not be of childbearing potential or, if of childbearing potential, have a negative pregnancy test prior to randomization.
* Randomization will apply to only 1 carotid artery occlusion for patients with bilateral carotid occlusion. Intervention of the contralateral stenosis, should it exists, may be done in according to clinical indications at least 30 days prior to randomization.

Exclusion Criteria randomized control study

* Patient has acute stroke within 90 days,
* Prior major ipsilateral stroke in the past with moderate disability (mRS ≥ 3) that is likely to confound study outcomes.
* Current neurologic illness characterized by fleeting or fixed neurologic deficits that cannot be distinguished from TIA or stroke.
* Patient has significant renal insufficiency with estimated glomerular filtration rate (eGFR) \<30 ml/min (at screening). and would not receive renal replacement therapy if contrast agent related nephropathy occurs
* Intolerance or allergic reaction to a study medication without a suitable management alternative.
* Patient is expected to have the ADP antagonist therapy interruption within 3 months after the procedure.
* GI hemorrhage within 1 month prior to enrollment that would preclude antiplatelet therapy
* Bleeding diathesis
* Intracranial hemorrhage within the past 12 months.
* Platelet count \<100,000/μl or history of heparin-induced thrombocytopenia.
* Other high-risk cardiac sources of emboli, including left ventricular aneurysm, severe cardiomyopathy, aortic or mitral mechanical heart valve, severe calcific aortic stenosis (valve area \< 1.0 cm2), endocarditis, moderate to severe mitral stenosis, left atrial thrombus, or any intracardiac mass, or known unrepaired PFO with prior paradoxical embolism.
* Major (non-carotid) surgery/procedures planned within 3 months after enrollment.
* Any major surgery, major trauma, revascularization procedure within the past 1 month.
* Acute coronary syndrome within the past 1 month or ACS that is not amenable to revascularization (patients should undergo planned coronary revascularization at least 30 days before randomization).
* Coronary artery disease with two or more proximal or major diseased coronary arteries with ≥ 70% stenosis that have not, or cannot, be revascularized.
* Inability to understand and cooperate with study procedures or provide informed consent.
* Patients with \< 5 years life expectancy
* Concomitant vascular conditions precluding endovascular revascularization procedure;
* Previous ipsilateral carotid artery stenting
* Intracranial aneurysm or arteriovenous malformation;
* Educational level lower than elementary school;
* Aphasia or right-sided hemiparesis
* Marked depression.
* Severe dementia.

Primary outcomes:
measure: NCF improvement by Alzheimer Disease Assessment Scale-Cognitive subscale (ADAS-Cog)
timeFrame: at 3 months and thereafter up to 12 months
measure: NCF improvement by Mini-Mental State Examination (MMSE)
timeFrame: at 3 months and thereafter up to 12 months
measure: NCF improvement by verbal fluency test
timeFrame: at 3 months and thereafter up to 12 months
measure: NCF improvement by verbal fluency test Color Trails Test Parts 1
timeFrame: at 3 months and thereafter up to 12 months
measure: NCF improvement by verbal fluency test Color Trails Test Parts 2
timeFrame: at 3 months and thereafter up to 12 months
Secondary outcomes:
measure: Death and stroke
timeFrame: within 30 days after the procedure and between 31 days and 1 year
measure: Major stroke, ischemic stroke, or hemorrhagic stroke
timeFrame: within 30 days after the procedure and between 31 days and 1 year
measure: Cambridge Neuropsychological Test Automated Battery (CANTAB)
timeFrame: at 3 months and thereafter up to 12 months
measure: Change of cerebral perfusion
timeFrame: at 3 months and thereafter up to 12 months
measure: Target vessel revascularization rate
timeFrame: one year
measure: Technique success rate
timeFrame: 30 days
measure: Procedure success rate
timeFrame: 30 days
Other outcomes:
measure: Major procedure complication
timeFrame: 30 days
measure: Bleeding complication
timeFrame: one year
Locations:
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: National Taiwan University Hospital
name: Hsien-Li Kao, MD
role: PRINCIPAL_INVESTIGATOR
References: