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

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

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.

Study Overview

• Status: Completed
• Conditions: Ischemic Stroke
• Intervention / Treatment: Device: NOVA Intracranial Sirolimus Eluting Stent System; Device: Apollo Intracranial Stent System

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.

• Study Type: Interventional
• Enrollment (Actual): 272
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100050
    • Beijing Tiantan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 18 to 75 years of age;
2. 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);
3. No transient ischemic attack (TIA) or ischemic stroke occurred within 2 weeks prior to stenting procedure;
4. ≥70% stenosis of intracranial responsible vessel under the DSA angiography (as judged through the WASID method);

5. 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;

6. 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;
7. Atherosclerosis lesions;
8. mRS < 3;
9. Written informed consent.

Exclusion Criteria:

1. >70% intracranial large-vessel stenosis beyond the responsible vessel;
2. >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;
3. Acute ischemic stroke within 3 weeks;
4. Obstruction of perforating branch artery under the skull MRI;
5. Intracranial hemorrhage in the angiopathic area within 6 weeks;
6. Patient was treated by thrombolytic therapy within 24 hours;
7. Patients underwent surgery within 30 days or plan for surgery within 3 months post-stenting procedure;
8. Severe calcified lesions;
9. Patients have been treated by intracranial/extracranial stenting procedures prior to this study;
10. Nonatherosclerosis lesions;
11. Patients with potential sources for cardiac embolism;
12. Concomitant intracranial tumor, aneurysm or intracranial arteriovenous malformation;
13. 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);
14. Hemoglobin <100g/L, platelet count <100,000 cells/mm3, International normalized ratio (INR) >1.5 (irreversible) or uncorrectable hemorrhagic factors;
15. Serious neural dysfunction due to the responsible angiopathy as the sequel of cerebral infarction (mRS≥3);
16. Known liver or renal insufficiency (ALT> 3x upper limit or AST > 3x upper limit, creatinine > 1.5x upper limit);
17. Life expectancy < 2 years;
18. Pregnant/lactating female patients;
19. Patients with cognitive impairment or mental diseases;
20. The patient participated in another investigational device or drug study within 3 months;
21. Inapplicable for intravascular stenting treatment as per investigators judgment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental; NOVA Intracranial sirolimus eluting stent system	Device: NOVA Intracranial Sirolimus Eluting Stent System; 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.
Active Comparator: Control; Apollo Intracranial stent system	Device: Apollo Intracranial Stent System; A 316L stainless steel balloon-expandable intracranial stent system

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	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

Collaborators and Investigators

• Sponsor: Sino Medical Sciences Technology Inc.
• Collaborators: Beijing Tiantan Hospital
• Investigators: Principal Investigator: Zhongrong Miao, M.D., Beijing Tiantan Hospital

Publications and helpful links

General Publications

• Jia B, Zhang X, Ma N, Mo D, Gao F, Sun X, Song L, Liu L, Deng Y, Xu X, Zhang Y, Liu Z, Guan S, Zhang F, Li B, Zheng H, Liu X, Liu Y, Chen K, Shuai J, Wan J, Wang J, Shi X, Li T, Chang B, Liebeskind DS, Yu W, Miao Z; NOVA Trial Investigators. Comparison of Drug-Eluting Stent With Bare-Metal Stent in Patients With Symptomatic High-grade Intracranial Atherosclerotic Stenosis: A Randomized Clinical Trial. JAMA Neurol. 2022 Feb 1;79(2):176-184. doi: 10.1001/jamaneurol.2021.4804.

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2015
• Primary Completion (Actual): January 1, 2020
• Study Completion (Actual): January 1, 2020

Study Registration Dates

• First Submitted: September 29, 2015
• First Submitted That Met QC Criteria: October 14, 2015
• First Posted (Estimate): October 16, 2015

Study Record Updates

• Last Update Posted (Actual): October 13, 2021
• Last Update Submitted That Met QC Criteria: October 11, 2021
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Ischemic Stroke; Intracranial Stenting
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: NOVA-001