Clinical trial NCT02578069: First-in-man Trial Evaluating the Safety and Efficacy of the NOVA Intracranial Stent (NOVA Trial)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Ischemic Stroke
Keywords: Ischemic Stroke
Intracranial Stenting
Lead sponsor: Sino Medical Sciences Technology Inc.
Sponsor class: INDUSTRY
Collaborators: name: Beijing Tiantan Hospital
First posted: 2015-10-16
Enrollment: 272
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: In stent restenosis rate (> 50% restenosis)
timeFrame: 12 months post-procedure
Secondary outcomes:
measure: Stroke and death events
timeFrame: within 30 days after stenting
measure: Target vessel ischemic stroke event
timeFrame: between 30 days and 1 year post-procedure
measure: Acute procedural success rate (stenosis < 30%)
timeFrame: 1 year
measure: Target vessel stroke or death events
timeFrame: within 30 days after stenting
measure: Non-target vessels ischemic stroke event
timeFrame: between 30 days and 1 year post-procedure
measure: Recurrent ischemic stroke in the involved vascular area
timeFrame: between 30 days and 1 year post-procedure
measure: Cerebral parenchyma hemorrhage, subarachnoid hemorrhage and intraventricular bleeding events
timeFrame: between 30 days and 1 year post-procedure
measure: Death event
timeFrame: between 30 days and 1 year post-procedure
measure: Transient ischemic attack event
timeFrame: within 1 year post-procedure
measure: National Institutes of Health Stroke Scale (NIHSS) evaluation
timeFrame: at 1 and 12 months
measure: modulate RANK score （mRS）evaluation
timeFrame: at 1 and 12 months
measure: Montreal Cognitive Assessment (MoCA) evaluation
timeFrame: at 1 and 12 months
measure: EQ-5D score evaluation
timeFrame: at 12 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tiantan Hospital
Study officials:
affiliation: Beijing Tiantan Hospital
name: Zhongrong Miao, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.