First-in-man Trial Evaluating the Safety and Efficacy of the NOVA Intracranial Stent (NOVA Trial)

Study Overview
=================
Brief Summary
-----------------
Prospective, multi-center, randomized 1:1 single blind trial using NOVA sirolimus eluting stent versus Apollo bare metal stent conducted in approximately 15 interventional neurology centers in China. The study was sponsored by Sino Medical Sciences Technology Inc.

Detailed Description
-----------------
The study will enroll 264 subjects overall in two groups (randomized 1:1). The study follow-up will occur at 1, 6 and 12 months post-stent implantation. All patients will undergo angiography assessment (DSA/CTA) at 12 months follow-up. Angiography assessment will be performed at baseline (pre- and post-procedure) and 12 months follow-up.

Official Title
-----------------
A Prospective, Multi-center, Randomized Controlled Study to Evaluate the Safety and Efficacy of the NOVA Sirolimus Eluting Stent Versus the Apollo Stent

Conditions
-----------------
Ischemic Stroke

Intervention / Treatment
-----------------
* Device: NOVA Intracranial Sirolimus Eluting Stent System
* Device: Apollo Intracranial Stent System


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18 to 75 years of age; Primary or recurrent symptomatic intracranial arteriostenosis through the internal medicine treatment (i.e. stroke or transient ischemic attack within 90 days during the treatment with at least one anti-thrombotic drugs and vascular risk factor intervention e.g. hypertensors for hypertension and hypolipidemics for hyperlipidemia); No transient ischemic attack (TIA) or ischemic stroke occurred within 2 weeks prior to stenting procedure; ≥70% stenosis of intracranial responsible vessel under the DSA angiography (as judged through the WASID method); Poor blood circulation in the side branch of responsible vessel area under the angiography within one week prior to stenting procedure: Score of blood circulation in the side branch under the DSA <3 or blood flow rate peak ≥200cm/s at the systolic phase under the transcranial doppler ultrasonic examination (TCD); or no apparent side branch compensation in the responsible vessel area under CTA or score of blood circulation in the side branch under the CTA <2; The target lesion reference diameter must be visually estimated to be ≥2.0 mm in diameter, and lesion length must be <15 mm; no lesion observed in the distal vessel; Atherosclerosis lesions; mRS < 3; Written informed consent. Exclusion Criteria: >70% intracranial large-vessel stenosis beyond the responsible vessel; >70% stenosis observed at the intracranial large-vessel distal to the responsible vessel or >70% stenosis observed at the intracranial/extracranial large-vessel proximal to the responsible vessel; Acute ischemic stroke within 3 weeks; Obstruction of perforating branch artery under the skull MRI; Intracranial hemorrhage in the angiopathic area within 6 weeks; Patient was treated by thrombolytic therapy within 24 hours; Patients underwent surgery within 30 days or plan for surgery within 3 months post-stenting procedure; Severe calcified lesions; Patients have been treated by intracranial/extracranial stenting procedures prior to this study; Nonatherosclerosis lesions; Patients with potential sources for cardiac embolism; Concomitant intracranial tumor, aneurysm or intracranial arteriovenous malformation; Known hypersensitivity or contraindication to aspirin, heparin, antiplatelet medication specified for use in the study, sirolimus, poly(lactic-co-glycolic acid) polymers, or poly(n-butyl methacrylate); Hemoglobin <100g/L, platelet count <100,000 cells/mm3, International normalized ratio (INR) >1.5 (irreversible) or uncorrectable hemorrhagic factors; Serious neural dysfunction due to the responsible angiopathy as the sequel of cerebral infarction (mRS≥3); Known liver or renal insufficiency (ALT> 3x upper limit or AST > 3x upper limit, creatinine > 1.5x upper limit); Life expectancy < 2 years; Pregnant/lactating female patients; Patients with cognitive impairment or mental diseases; The patient participated in another investigational device or drug study within 3 months; Inapplicable for intravascular stenting treatment as per investigators judgment.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>NOVA Intracranial sirolimus eluting stent system | Device: NOVA Intracranial Sirolimus Eluting Stent System<br>* A sirolimus eluting intracranial stent system with polylactic-co-glycolic acid (PLGA) biodegradable drug carrier and electro-grated polybutyl methacrylate (PBMA) base coating. The stent platform is made of 316L stainless steel.<br>|
| Active Comparator: Control<br>Apollo Intracranial stent system | Device: Apollo Intracranial Stent System<br>* A 316L stainless steel balloon-expandable intracranial stent system<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In stent restenosis rate (> 50% restenosis) | Angiography assessment at 12 months post-procedure | 12 months post-procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stroke and death events |  | within 30 days after stenting | 
| Target vessel ischemic stroke event |  | between 30 days and 1 year post-procedure | 
| Acute procedural success rate (stenosis < 30%) |  | 1 year | 
| Target vessel stroke or death events |  | within 30 days after stenting | 
| Non-target vessels ischemic stroke event |  | between 30 days and 1 year post-procedure | 
| Recurrent ischemic stroke in the involved vascular area |  | between 30 days and 1 year post-procedure | 
| Cerebral parenchyma hemorrhage, subarachnoid hemorrhage and intraventricular bleeding events |  | between 30 days and 1 year post-procedure | 
| Death event |  | between 30 days and 1 year post-procedure | 
| Transient ischemic attack event |  | within 1 year post-procedure | 
| National Institutes of Health Stroke Scale (NIHSS) evaluation |  | at 1 and 12 months | 
| modulate RANK score （mRS）evaluation |  | at 1 and 12 months | 
| Montreal Cognitive Assessment (MoCA) evaluation |  | at 1 and 12 months | 
| EQ-5D score evaluation |  | at 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Ischemic Stroke, Intracranial Stenting