Enterprise Stent Implantation in the Treatment of Carotid Artery Stenosis With Ischemic Stroke
Enterprise Stent Implantation in the Treatment of Carotid Artery Stenosis With Ischemic Stroke
To investigate the long-term effects of intracranial implantation of Enterprise stent system
 versus antiplatelet medication on neurologic deficits, daily living abilities, and carotid
 artery stenosis in patients with atherosclerotic ischemic stroke.
Atherosclerosis is a chronic degenerative disease that can cause intracranial carotid artery
 stenosis, which is a leading cause of ischemic stroke. The currently used interventions for
 carotid artery stenosis in ischemic stroke include internal medication, carotid
 endarterectomy (CEA) and carotid angioplasty and stenting (CAS). Internal medication for
 carotid artery stenosis is mainly performed to reduce risk factors for cerebrovascular
 disease, including anti-platelet aggregation, anticoagulation, lowering blood lipid and blood
 pressure, controlling blood glucose and improving living habits. As for patients with mild
 carotid artery stenosis, internal medication is generally recommended. Carotid endarterectomy
 has been confirmed to be a gold standard for the treatment of carotid artery stenosis.
 However, it is also limited by some factors including sophisticated technique, great trauma,
 general anesthesia, severe stroke, 9% fatality rate, and 7.6% cranial nerve injury. In
 addition, carotid endarterectomy is not suitable for patients with high-position or tandem
 carotid artery stenosis or carotid artery stenosis complicated by contralateral carotid
 artery occlusion. In recent years, CAS has been increasingly used for the treatment of
 carotid artery stenosis in patients with ischemic stroke because of its minimally invasive
 procedure, rapid recovery process and wide indications.

 Enterprise stent system is a U.S. Food and Drug Administration (FDA)-approved closed loop
 recoverable self-expanding stent that has been confirmed to be highly effective in the
 treatment of intracranial aneurysm. Existing evidence on use of Enterprise stent system for
 intracranial artery stenosis in patients with ischemic stroke mainly focus on case series and
 case reports.

 There is a lack of randomized controlled trial evidence regarding long-term effects of
 Enterprise stent implantation for the treatment of carotid artery stenosis after ischemic
 stroke. The existing related reports are case series or case reports with the caveats like
 non-randomized, non-blinded design with small sample sizes. Therefore, in this study, the
 investigators designed a double-blind, randomized, drug control trial to investigate the
 efficacy of Enterprise stent implantation in the treatment of carotid artery stenosis in
 patients with ischemic stroke.

 Enterprise stent system is a novel closed loop self-expanding stent that is made of Ni-Ti
 alloy and shows favorable flexibility and ease in use, and its use was approved in 2009 in
 China. The current clinical evidence regarding use of Enterprise stent system mainly address
 on aneurismal treatment. In this study, the investigators will use Enterprise stent system to
 treat carotid artery stenosis in patients with ischemic stroke, which is of important
 clinical significance for secondary prevention of ischemic stroke. In addition, there is no
 long-term follow-up evidence regarding Enterprise stent implantation of carotid artery
 stenosis after ischemic stroke, so 3-year follow-up will be performed in this study.

 In this study, simple antiplatelet drug will be used as controls to investigate the
 superiority of Enterprise stent implantation in combination with antiplatelet over
 antiplatelet medication only in the treatment of carotid artery stenosis. Outcomes from this
 study will add objective, rigorous, double-blind, randomized, controlled long-term follow-up
 trial evidence to Enterprise stent implantation for the treatment of carotid artery stenosis
 after ischemic stroke.

 Adverse events Possible adverse events associated with Enterprise stent implantation include
 puncture site hematoma, vascular spasm, bradycardia, hypotension, cerebral hyperperfusion
 syndrome, device shifting, local ischemia, vascular occlusion, ischemic stroke,
 intraoperative hypertension, postoperative hypotension and hypoglycemia. If adverse events
 occur, details of the event including the date of occurrence, measures taken related to the
 treatment, causal relationship with the treatment and treatment of the adverse event will be
 reported to the principal investigator and the institutional review board within 24 hours.

 Data collection, management, analysis and open access All data will be collected in case
 report forms and collated. Collated data will be input into an electronic database using a
 double-data entry strategy by trained professional stall. Information accuracy will be
 checked when all included patients will be followed up. The collected data will be locked by
 a researcher in charge and will not be altered for later review. All data related to this
 trial will be preserved by Beijing Chao-yang Hospital, Capital Medical University, China. The
 electronic database will be fully known to a professional statistician for statistical
 analysis. Anonymized trial data will be published at http://www.figshare.com.

 Statistical analysis All data will be statistically analyzed by a statistician blinded to
 randomization using SPSS 17.0 software. The successive normally distributed variables will be
 expressed as the mean ± SD. The non-normally distributed variables will be expressed as
 median and quartile. Classification variables will be expressed as counts and the percentage.
 Two-sample t-test (normally distributed data) or Mann-Whitney U test (non-normally
 distributed data) will be used for comparison of NIHSS score and Barthel index between stent
 implantation and drug groups. Chi-square test or Fisher's exact test will be used for
 comparison of carotid stenosis rate between these two groups. A level of P < 0.05 will be
 accepted as statistically significant.

 Auditing Trial progression will be reported to the ethics committee of Beijing Chao-yang
 Hospital, Capital Medical University, China every 1 year and the trial's status will be
 updated in the registration database.

 Confidentiality Trial data include paper and electronic forms. Electronic data will be
 preserved in a dedicated password-protected computer and managed by a data management
 professional. Data reported on paper will be preserved in a secure, locked place for future
 viewing.
Inclusion Criteria:

 -  Atherosclerotic plague-caused carotid artery stenosis

 -  Severe carotid artery stenosis (unilateral stenosis > 70%) diagnosed according to
 angiography

 -  Age 18-75 years

 -  Of either sex

 -  Provision of informed consent regarding trial procedure

 Exclusion Criteria:

 -  Non-atherosclerotic intracranial artery stenosis

 -  Severe cognitive or mental disorder

 -  Severe cardiovascular, hepatic, renal, or blood system diseases

 -  Pregnant or lactating

 -  Hemorrhagic disease or unable to receive anticoagulation or antiplatelet aggregation
 treatment

 -  Allergy to stent material

 -  Unable to or declined to cooperate with follow-up examination

 -  Unable to provide informed consent because of intellectual disability or language
 disorder