Clinical trial NCT03381534: Safety and Efficacy of Distal Embolic Protection Device in Vertebral Artery Origin Stenting
Official title: Safety and Efficacy of Distal Embolic Protection Device in Vertebral Artery Origin Stent Angioplasty :A Prospective, Multicenter, Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Adverse Event
Keywords: vertebral artery origin
angioplasty
distal embolic protection
Lead sponsor: Xuanwu Hospital, Beijing
Sponsor class: OTHER
First posted: 2017-12-22
Enrollment: 256
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a prospective single-center,randomized controlled trial,aiming to investigate the safety and efficacy of distal EPD in vertebral artery origin stenting(VAOS);256 subjects will be recruited in this study,after randomized recruitment, treatment group(128 subjects each group) undergo VAOS with adjuvant distal embolic protection device（EPD）,control group undergo routine VAOS without distal embolic protection device.Intraprocedural and postprocedural in-hospital adverse events,including stroke,death and dis-retrieval of EPD,will be noted and cost-effectiveness analysis also will be conduct,including economic cost,hospital stays.

Detailed description: Ischemic cerebrovascular diseases are associated with a high rate of mortality and disability rate, as a consequence, many related trials were conducted to perfect prophylaxis and treatment of ischemic stroke. 2/3 of cerebral blood supply is offered by Internal carotid artery(ICA) , due to high morbility and disability rate of carotid territory stroke, stoke caused by ICA stenosis is always emphasized by authors. With the development to the depth in this field, ischemic stroke in posterior circulation related to vertebral artery stenosis is gradually paid attention recently. Outcome from New England medical center posterior circulation registry study revealed that 20% of patients were found to have vertebral artery origin(VAO) stenosis, in 9% of these patients, no other cause of stroke was identified. The relative risk of having a stroke or dying in patients with VAO stenosis was 6 times than that of patients without VAO stenosis. Therefore, VAO stenosis need appropriate management to prevent potentiality of ischemic stroke.

Nowadays there are three treatment alternatives for extracranial VAO stenosis: medicine, surgery and endovascular stent angioplasty. However, medical therapy mainly focus on prevention and delay of severe ischemic events other than radical therapy, and it's not always effective to improve symptoms of posterior circulation ischemia. Surgery are limited by its serious trauma and the combined postoperative morbidity and mortality rates ranging from 10% to 20%.Endovascular stent angioplasty was feasible in ICA stenosis as reported in literatures, and that promotes the utilization of stent in VAO stenosis in recent years. Related retrospective studies have demonstrated the safety and efficacy of vertebral artery origin stenting(VAOS) in VAO stenosis. In a Meta analysis that summarized 27 articles about extracranial vertebral artery stenting, Stayman observed that the rate of transient ischemic attack(TIA) and stroke within postprocedural 30 days was 1.1% and 0.8% respectively. Compter etc. are conducting a prospective case-control study to assess the safety and feasibility of VAOS, which final outcome is thought to be relatively authentic.

However, some drawbacks in VAOS needs additional resolution, like embolization caused by plaque debris, high restenosis rate, vasospasm, vessel dissection. Especially, embolization is associated with not only plaque characteristic, but also anatomy of the vertebral arteries, which is potentially essential to high risk of plaque debris dislodgment. The origin of vertebral artery is characterized with small diameter and tortuous course. Dodevski analyzed 30 patients' vertebral arteries and found that 40% of patients' vertebral artery was tortuous, the diameter of the VAO on the left side was in the range between 1.60-5.2 mm, mean 3.33 ± 0.89 mm, and on the right side from 1.64-5.40 mm, mean 3.19 ± 0.98 mm. Tortuosity and small diameter in VAO will increase operation difficulty and procedural time. Borhanisummarized 27 articles focusing on vertebral origin angioplasty and concluded that of the 808 patients underwent stent angioplasty, the combined rate of stroke and TIA within 1 month after stenting was 6.9%.

Concerning dislodgement of plaque debris, embolic protection device(EPD) is applied recently to decrease the risk of embolization. But utilization of EPD in VAOS is mainly based on its safety and feasibility in carotid artery stenting(CAS). In CAS, cerebral embolic protection devices can effectively reduce the incidence of transient ischemic attack, stroke and other related adverse events. The U.S. Safety Committee recommended stopping unprotected CAS, because the 30-day rate of stroke was 3.9 times higher than that of CAS with cerebral protection. However, VAOS is different from CAS, and its performance in CAS cann't serve as medical science evidence for distal EPD in VAOS. Firstly, the rate of postoperative restenosis after VAOS is higher than that of CAS, ranging from 20% to 66.7%.Secondly, VAO are characterized by concentric, fibrous, and smooth lesions with lower incidence of ulceration and intraluminal hemorrhage compared with extracranial carotid artery circulation\[13\]. Thirdly, the microscopic structure of VAO is featured with elastic fibers and smooth muscles. These distinctions indicate that investigators should make a distinction between CAS and VAOS in terms of intravascular intervention. As to the use of EPD in VAOS, no Class Ⅰ evidence can verify the safety and efficacy of EPD and clinicians share discrepant opinions. Some authors thought that distal protection devices will suspend operation process, increase operation-related risk and may cause embolization during crossing lesion and retrieval which may be referable to transient shear stress. In addition, some patients are intolerable to flow cessation caused by distal EPD. Moreover, foreign case reports even noted that utilization of distal EPD was probable to induce vasospasm and difficult retrieval of distal EPD was finally managed by secondary surgery in some cases\[14, 15\]. However, small sample-size studies demonstrated it's safe and feasible to use distal EPD in VAOS. Qureshi etc.retrospectively analyzed clinical data of 12 patients underwent VAOS with filter protection, outcome revealed that no stroke and death events occured within 1 month follow-up. In a multicenter study, Edgell etc. contrastively analyzed the data of patients underwent VAOS with and without distal EPD, the rate of TIA and stroke within 1 month between the two groups showed no significant difference. Divani etc. analyzed plaque debris captured by EPDs in 14 patients who underwent VAOS with distal protection devices, the outcome revealed that relative to the size of the filter, the proportion of captured debris ranged from 0.1% to 22% in the VA filters, hence, Divani recommended the use of distal EPD in VAOS.

In summary, the use of distal EPD in VAOS is debatable, no class I evidence can support the advantage of use of distal EPD in VAOS. Here, the investigators will conduct this prospective, single-center, randomize controlled trial aiming to analyzed the safety and efficacy of distal EPD in VAOS.

Eligibility criteria: Inclusion Criteria:

1. Aged 40 to 80 years old;
2. VAO atherosclerotic stenosis results in posterior circulation ischemic symptom refractory to best medical treatment;
3. symptomatic VAO atherosclerotic stenosis\>70% evaluated by computed tomograph angiography(CTA) or Magnetic Resonance Angiography(MRA) or digital subtraction angiography(DSA);
4. the diameter of the normal segment of the artery beyond the stenosis \>3.5mm;
5. written informed consent.

Exclusion Criteria:

1. VAO stenosis is combined with ipsilateral vertebrobasilar disease including severe cranial vertebral artery stenosis and severe basilar artery stenosis.
2. VAO is occluded;
3. Patients who will be underwent bilateral VAOS due to bilateral VAO stenosis including someone with bilateral VAO stenosis \>70% and the patient who need contralateral VAOS after stenting in unilateral VAO due to recurrent posterior circulation ischemia refractory to best medical treatment.
4. VAO stenosis caused by arteritis,artery dissection, aplasia, vasculopathy caused by radiotherapy etc, other than atherosclerosis;
5. stroke within 30 days or myocardial infarction within 6 months;
6. contraindication of anticoagulant and antiplatelet agents; allergy to iodinated contrast agent;
7. severe comorbid diseases and intolerant to procedure; patient unlikely to cooperate with the procedure or provide informed consent.
8. High risk of difficulty or failure in EPD advance and retrieval due to the tortuosity of the culprit vertebral artery origin.

Primary outcomes:
measure: embolus capture rate in patients treated with VAO stenting with EPD
timeFrame: during procedure
Secondary outcomes:
measure: incidence of ischemic stroke in the two group
timeFrame: 30 days after procedure
measure: incidence of disable or fatal ischemic stroke in EPD group
timeFrame: 1 month after procedure
Other outcomes:
Locations:
city: Beijing
country: China
facility: XuanWu hospital
Study officials:
affiliation: Xuanwu Hospital of Capital Medical University
name: Jiao Li Qun, MD
role: PRINCIPAL_INVESTIGATOR
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