Clinical trial NCT03703635: Balloon Angioplasty for Symptomatic Intracranial Artery Stenosis
Official title: A Multicenter, Prospective, Randomized, Open-label, Blinded End-point Clinical Study to Evaluate the Safety and Efficacy of Intracranial Balloon Angioplasty Plus Aggressive Medical Management for Symptomatic Intracranial Artery Stenosis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Intracranial Artery Stenosis
Keywords: ICAD
Intracranial Artery Stenosis
Ischemic Stroke
TIA
Angioplasty
Aggressive Medical Care
Lead sponsor: Ministry of Science and Technology of the People´s Republic of China
Sponsor class: OTHER_GOV
First posted: 2018-10-12
Enrollment: 512
Sex: ALL
Minimum age (years): 35
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Intracranial atherosclerotic disease (ICAD) is the most common cause of ischemical cerebrovascular events. The risk of stroke recurrence or death of ICAD patients remains very high. Even with aggressive medical management including dual antiplatelet therapy and strict management of risk factors, 12.2 percent of patients with 70-99 percent stenosis of intracranial artery had stroke or death during 1 year follow-up. In the real world, the 30-day risk of recurrent stroke of patients with aggressive medical management was as high as 20.2 percent. Balloon angioplasty and stent for intracranial artery have become important alternative treatments to prevent recurrent stroke for patients with severe intracranial atherosclerotic stenosis. Nevertheless, the SAMMPRIS trial has suggested intracranial stenting has higher stroke and death rate than aggressive medication with high peri-procedure complication rate. Previous nonrandomized studies have showed that stroke and death rate of angioplasty for ICAD patients with severe stenosis of intracranial artery is lower than that of aggressive medication. The primary purpose of this trial is to compare intracranial angioplasty plus aggressive medical management with aggressive medical management alone for the treatment of patients with 70-99 percent intracranial artery stenosis because of ICAD and to clarify the efficacy and safety of intracranial angioplasty through a multicenter, prospective, randomized, open-label, blinded end-point trial.

Detailed description: This trial is a multicenter, prospective, randomized, parallel controlled trial. A total of approximately 512 patients (35-80 years of age) with primary or recurrent sICAS (a recent TIA\[\<90 days\] or ischemic stroke \[14-90 days\] before enrollment attributed to 70-99% atherosclerotic stenosis of a major intracranial artery) receiving treatment with at least one antithrombotic drug and/or standard medical management of vascular risk factors will be enrolled. Patients fulfilling all of the inclusion criteria and none of the exclusion criteria will be randomized into two groups according to the 1:1 ratio after offering informed content: 1) Experimental group will receive intracranial angioplasty plus aggressive medical management which is the same as the control group; 2) Control group will receive aggressive medical management only. Aggressive medical management includes 100 mg/day of aspirin during the follow-up period; 75 mg/day of clopidogrel within 90 days after enrollment, and whether clopidogrel should continue to be used depends on the actual situation of the subjects; 20-80mg/day of atorvastatin should be used during the year after enrollment, and dose adjustment to target LDL \<1.8mmol/L or \<70 mg/dl. Both groups will receive risk factors management including blood pressure to maintain 130-140/80-90 mmHg and LDL lower than 70 mg/dl or 1.8mmol/L. The primary objective is to evaluate the safety and efficacy of intracranial angioplasty combined with aggressive medical management for symptomatic intracranial artery stenosis. The study consists of 11 visits including the day of screening and randomization, the day when the subject receive intracranial angioplasty and/or aggressive medical management, the day before the subject is discharged from hospital, 30, 90,180 days and 1 year after enrollment, and every half a year after then until the third year. Demographic information, symptoms and signs, laboratory test, neuro-imaging assessment neurological function rating scale will be recorded during the program. The trial is anticipated to last from October 2018 to May 2025 with 512 subjects recruited from 31 centers in China. All the related investigative organization and individuals will obey the Declaration of Helsinki and Chinese Good Clinical Practice standard. A Data and Safety Monitoring Board (DSMB) will regularly monitor safety during the study. The trial has been approved by the ethics committee of Beijing Tiantan Hospital and corresponding branch centers.

Eligibility criteria: Inclusion Criteria:

1. Age 35-80 years.
2. Participants with primary or recurrent sICAS (a recent TIA\[\<90 days\] or ischemic stroke \[14-90 days\] before enrollment attributed to 70-99% atherosclerotic stenosis of a major intracranial artery) receiving treatment with at least one antithrombotic drug and/or standard medical management of vascular risk factors;
3. Diagnosed by DSA: a major intracranial artery (terminal internal carotid artery \[ICA\] \[C4-C7 segments\], middle cerebral artery \[MCA\] M1 segment, vertebral artery \[VA\] V4 segment, and basilar artery \[BA\]) severe atherosclerotic stenosis (70-90% according to WASID method) with lesion length ≤ 10mm, diameter ≥1.5mm, and normal distal artery. (Regarding the curvature and angle of the lesion, whether the patient is enrolled in BASIS per the investigator's determination based on the patient's situation);
4. Informed consent signed.

Exclusion Criteria:

1. Surgery within the past 30 days or plan to receive ≥ 3-grade surgery within 90 days;
2. Thrombolytic therapy within 24 hours before enrollment;
3. Neurological deficits worsen within 24 hours before enrollment;
4. Acute ischemic stroke onset within 14 days before enrollment;
5. Other intracranial arteries with severe stenosis (70-99%) besides the target artery and its supplying artery;
6. Target artery's supplying artery stenosis \> 50%. For example, patient with MCA severe stenosis (target artery) and the ipsilateral ICA stenosis \> 50% should be excluded; patient with BA severe stenosis (target artery) and the dominant VA stenosis \> 50% should be excluded; the patient with extracranial artery (non-lesion side) stenosis \> 70% should be excluded; For patients with balanced VA, if bilateral VA stenosis \> 70% at the same time, should be excluded (unable to determine which VA is the lesion artery). However, if patient's dominant VA is the lesion artery with a dysplasia or slender contralateral VA or a non-dominant contralateral VA terminating at posteroinferior cerebellar artery, should not be excluded.
7. Participant with perforator stroke (except for severe stenosis of supplying artery combined with hemodynamic compromise or poor collaterals) 12;
8. Baseline modified Rankin Scale ≥ 3;
9. Non-atherosclerotic diseases (e.g., arterial dissection, moyamoya disease, vascular inflammatory lesions caused by infection, autoimmune diseases, post-irradiation, postpartum status; developmental or genetic abnormalities such as fibromuscular dysplasia, sickle cell anemia, suspected vasospasm);
10. Target artery with severely calcified and adjacent to stenosis;
11. Suspected ischemic event caused by embolism or the arterial embolism from extracranial segment (ipsilateral chest or neck vascular occlusive disease) or potential cardioembolism (e.g., atrial fibrillation, mitral stenosis, patent foramen ovale, left ventricular thrombus, myocardial infarction within 6 weeks, etc.);
12. Coexistent with Intracranial tumors, aneurysms or intracranial arteriovenous malformations;
13. Intracranial hemorrhage within the past 3 months, including parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, epidural hemorrhage or subdural hemorrhage, etc.;
14. Angioplasty procedure (including balloon dilatation, stenting, or endarterectomy) performed at the original target vessel or its primary supplying artery, or a planned stenting procedure;
15. Unable to receive dual antiplatelet therapy due to other diseases;
16. Tortuous vascular approach that cannot be stabilized to obtain vascular access;
17. Allergic to heparin, aspirin, clopidogrel, contrast agents, anesthetics, and balloon components;
18. Hemoglobin \< 100g/L, platelet count \< 100×109/ L, international normalized ratio (INR) \>1.5 (irreversible), Coagulation dysfunction or uncorrectable bleeding factors;
19. Severe liver or kidney dysfunction. ALT \> three-fold higher than the upper limit of normal value or AST \> three-fold higher than the upper limit of normal value, or serum creatinine \> two-fold higher than the upper limit of normal value;
20. Pregnant and lactating women;
21. Participants with renal artery, radial artery, and cardiac coronary artery requiring concurrent intervention;
22. Expected survival expectation is less than\< 1 year;
23. Unable to complete follow-up due to mental illness, cognitive or emotional disorders;
24. Participants participating in other drug/medical device clinical trials who have not yet completed the program requirements;
25. Participants are not suitable for BASIS trial per investigator's opinion.

Primary outcomes:
measure: Stroke or death within 30 days after enrollment or after balloon angioplasty procedure of the qualifying lesion during follow-up, or any ischemic stroke or revascularization from the qualifying artery beyond 30 days through 12 months after enrollment
timeFrame: 12 months
Secondary outcomes:
measure: Any stroke (ischemic or hemorrhage stroke) or all-cause deaths within 30 days after enrollment or after balloon angioplasty procedure of the qualifying lesion during follow-up
timeFrame: 30 days
measure: Any stroke (ischemic or hemorrhage stroke) inside of the territory of the target artery or all-cause deaths within 90 days after enrollment
timeFrame: 90 days
measure: Any stroke (ischemic or hemorrhage stroke) outside of the territory of the target artery within 90 days after enrollment
timeFrame: 90 days
measure: Neurological improvement assessed by mRS at 90 days
timeFrame: 90 days
measure: Any stroke (ischemic or hemorrhage stroke) inside of the territory of the target artery or all-cause deaths within 12 months after enrollment
timeFrame: 12 months
measure: Revascularization of the target artery within 12 months after enrollment
timeFrame: 12 months
measure: Any stroke (ischemic or hemorrhage stroke) outside of the territory of the target artery within 12 months after enrollment
timeFrame: 12 months
measure: Neurological improvement assessed by mRS at 12 months
timeFrame: 12 months
measure: Restenosis rate of the target artery within 12 months (defined as rate of stenosis >70% or increased by 30% based on following-up neurovascular imaging)
timeFrame: 12 months
measure: Combined events such as stroke, myocardial infarction, and vascular death within 12 months after enrollment
timeFrame: 12 months
measure: Life quality assessment (EuroQol-5-Dimensions Scale [EQ-5D] questionnaire) within 12 months after enrollment
timeFrame: 12 months
measure: Any stroke (ischemic or hemorrhage stroke) inside of the territory of the target artery or all-cause deaths within 24 months after enrollment
timeFrame: 24 months
measure: Any stroke (ischemic or hemorrhage stroke) outside of the territory of the target artery within 24 months after enrollment
timeFrame: 24 months
measure: Neurological improvement assessed by mRS at 24 months
timeFrame: 24 months
measure: Combined events such as stroke, myocardial infarction, and vascular death within 24 months after enrollment
timeFrame: 24 months
measure: Any stroke (ischemic or hemorrhage stroke) inside of the territory of the target artery or all-cause deaths within 36 months after enrollment
timeFrame: 36 months
measure: Any stroke (ischemic or hemorrhage stroke) outside of the territory of the target artery within 36 months after enrollment
timeFrame: 36 months
measure: Neurological improvement assessed by mRS at 36 months
timeFrame: 36 months
measure: Combined events such as stroke, myocardial infarction, and vascular death within 36 months after enrollment
timeFrame: 36 months
Other outcomes:
Locations:
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
state: Anhui
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui University of CM
state: Anhui
city: Beijing
country: China
facility: Beijing Chao-Yang Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing Fengtai You Anmen Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Tian Tan Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Dongfang Hospital Beijing University of Chinese Medicine
state: Beijing
city: Beijing
country: China
facility: Chinese PLA General Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Luhe Hospital,Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing ShunYi Hospital
state: Beijing
city: Guangzhou
country: China
facility: The First Affiliated Hospital,Sun Yat-sen University
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong Provincial Hospital of Traditional Chinese Medicine
state: Guangdong
city: Guangzhou
country: China
facility: The Second Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong Sanjiu Brain Hospital
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen Hospital of Southern Medical University
state: Guangdong
city: Guiyang
country: China
facility: The Affiliated Hospital of Guizhou Medical University
state: Guizhou
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Wuhan
country: China
facility: Wuhan NO.1 Hospital
state: Hubei
city: Changsha
country: China
facility: Hunan Provincial People's Hospital
state: Hunan
city: Changzhou
country: China
facility: The First People's Hospital of Changzhou
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School
state: Jiangsu
city: Nanjing
country: China
facility: The Second Affiliated Hospital Of NanJing Medical University
state: Jiangsu
city: Nanchang
country: China
facility: Jiangxi Provincial People's Hospital
state: Jiangxi
city: Chang chun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Shenyang
country: China
facility: General Hospital of The Northern Theater of The Chinese People's Liberation Army
state: Liaoning
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Jinan
country: China
facility: Shandong Provincial Hospital
state: Shandong
city: Liaocheng
country: China
facility: LiaochengI People's Hospital
state: Shandong
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
state: Shandong
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shanxi
city: Xian
country: China
facility: The Affiliated Hospital of Northwest University
state: Shanxi
city: Chendu
country: China
facility: West China Hospital Sichuan University
state: Sichuan
Study officials:
affiliation: Beijing Tiantan Hospital
name: Zhongrong Miao, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Tiantan Hospital
name: Yilong Wang, MD
role: PRINCIPAL_INVESTIGATOR
References: