Balloon Angioplasty for Symptomatic Intracranial Artery Stenosis

Intracranial Artery Stenosis Clinical Trial

— BASIS  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03703635
• Other study ID #: 2017YFC1307900
• Status: Active, not recruiting
• Phase: N/A
• Start date: October 17, 2018
• Est. completion date: May 2025

Study information

• Verified date: June 2023
• Source: Ministry of Science and Technology of the People´s Republic of China
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 512
• Est. completion date: May 2025
• Est. primary completion date: May 2, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 35 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Constriction, Pathologic
• Intracranial Artery Stenosis

Intervention

Device:
• intracranial balloon angioplasty
A balloon (recommending the Neuro RX and Neuro LPS Intracranial Balloon Dilation Catheter [Sinomed Inc., Tianjin, China]) is navigated by the microwire to the lesion of the target artery.

Drug:
• aggressive medical management
Aspirin 100mg once/day during the follow-up period, Clopidogrel 75mg once/day for at least 90 days, Atorvastatin 20-80mg once/day as the situation requires and risk factors management including blood pressure to maintain 130-140/80-90 mmHg and LDL lower than 70 mg/dl or 1.8mmol/L.

Locations

Country	Name	City	State
China	Beijing Chao-Yang Hospital, Capital Medical University	Beijing	Beijing
China	Beijing Fengtai You Anmen Hospital	Beijing	Beijing
China	Beijing Luhe Hospital,Capital Medical University	Beijing	Beijing
China	Beijing ShunYi Hospital	Beijing	Beijing
China	Beijing Tian Tan Hospital, Capital Medical University	Beijing	Beijing
China	Chinese PLA General Hospital	Beijing	Beijing
China	Dongfang Hospital Beijing University of Chinese Medicine	Beijing	Beijing
China	The First Hospital of Jilin University	Chang chun	Jilin
China	Hunan Provincial People's Hospital	Changsha	Hunan
China	The First People's Hospital of Changzhou	Changzhou	Jiangsu
China	West China Hospital Sichuan University	Chendu	Sichuan
China	Guangdong Provincial Hospital of Traditional Chinese Medicine	Guangzhou	Guangdong
China	Guangdong Sanjiu Brain Hospital	Guangzhou	Guangdong
China	The First Affiliated Hospital,Sun Yat-sen University	Guangzhou	Guangdong
China	The Second Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong
China	The Affiliated Hospital of Guizhou Medical University	Guiyang	Guizhou
China	The First Affiliated Hospital of Anhui Medical University	Hefei	Anhui
China	The First Affiliated Hospital of Anhui University of CM	Hefei	Anhui
China	Qilu Hospital of Shandong University	Jinan	Shandong
China	Shandong Provincial Hospital	Jinan	Shandong
China	LiaochengI People's Hospital	Liaocheng	Shandong
China	Jiangxi Provincial People's Hospital	Nanchang	Jiangxi
China	Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School	Nanjing	Jiangsu
China	The Second Affiliated Hospital Of NanJing Medical University	Nanjing	Jiangsu
China	The Affiliated Hospital of Qingdao University	Qingdao	Shandong
China	General Hospital of The Northern Theater of The Chinese People's Liberation Army	Shenyang	Liaoning
China	Shenzhen Hospital of Southern Medical University	Shenzhen	Guangdong
China	Wuhan NO.1 Hospital	Wuhan	Hubei
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shanxi
China	The Affiliated Hospital of Northwest University	Xian	Shanxi
China	Henan Provincial People's Hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Ministry of Science and Technology of the People´s Republic of China

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	This outcome includes ischemic/hemorrhagic stroke and all-cause death within 30 days after enrollment or after balloon angioplasty procedure of the qualifying lesion during follow-up, or any ischemic stroke and revascularization from the original culprit symptomatic intracranial artery beyond 30 days through 12 months after enrollment.	12 months
Secondary	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	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.	30 days
Secondary	Any stroke (ischemic or hemorrhage stroke) inside of the territory of the target artery or all-cause deaths within 90 days after enrollment	Rat of any stroke (ischemic or hemorrhage stroke) inside of the territory of the target artery or all-cause deaths within 90 days after enrollment.	90 days
Secondary	Any stroke (ischemic or hemorrhage stroke) outside of the territory of the target artery within 90 days after enrollment	Rat of any stroke (ischemic or hemorrhage stroke) outside of the territory of the target artery within 90 days after enrollment.	90 days
Secondary	Neurological improvement assessed by mRS at 90 days	Modified Rankin Scale (mRS score) ranged from 0 to 6 is used to measure the recovery of neurological function in patients after stroke. Score 0 means completely no symptom. Score 6 means death. Higher values represent a worse outcome.	90 days
Secondary	Any stroke (ischemic or hemorrhage stroke) inside of the territory of the target artery or all-cause deaths within 12 months after enrollment	Rat of any stroke (ischemic or hemorrhage stroke) inside of the territory of the target artery or all-cause deaths within 12 months after enrollment.	12 months
Secondary	Revascularization of the target artery within 12 months after enrollment	Rat of revascularization of the target artery within 12 months after enrollment.	12 months
Secondary	Any stroke (ischemic or hemorrhage stroke) outside of the territory of the target artery within 12 months after enrollment	Rat of any stroke (ischemic or hemorrhage stroke) outside of the territory of the target artery within 12 months after enrollment.	12 months
Secondary	Neurological improvement assessed by mRS at 12 months	Modified Rankin Scale (mRS score) ranged from 0 to 6 is used to measure the recovery of neurological function in patients after stroke. Score 0 means completely no symptom. Score 6 means death. Higher values represent a worse outcome.	12 months
Secondary	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)	Restenosis is defined as rate of stenosis >70% or increased by 30% based on following-up neurovascular imaging.	12 months
Secondary	Combined events such as stroke, myocardial infarction, and vascular death within 12 months after enrollment	Combined events include stroke, myocardial infarction and vascular death etc; Myocardial infarction occurs when blood stops flowing properly to a part of the heart, and the heart muscle is injured because it is not receiving enough oxygen; vascular death means the death is due to vessel rupture or clot.	12 months
Secondary	Life quality assessment (EuroQol-5-Dimensions Scale [EQ-5D] questionnaire) within 12 months after enrollment	Quality of life evaluated by EuroQol-5-Dimensions Scale (EQ-5D) questionnaire at the 12 months follow-up. EQ-5D descriptive system covers five dimensions including mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has three response levels (no problem, some problems, and severe problems). The EQ-5D descriptive system generates 243 health states, each of which was assigned a utility. score ranging from -0.59 to 1.00 (full health)	12 months
Secondary	Any stroke (ischemic or hemorrhage stroke) inside of the territory of the target artery or all-cause deaths within 24 months after enrollment	Rat of any stroke (ischemic or hemorrhage stroke) inside of the territory of the target artery or all-cause deaths within 24 months after enrollment.	24 months
Secondary	Any stroke (ischemic or hemorrhage stroke) outside of the territory of the target artery within 24 months after enrollment	Rat of any stroke (ischemic or hemorrhage stroke) outside of the territory of the target artery within 24 months after enrollment.	24 months
Secondary	Neurological improvement assessed by mRS at 24 months	Modified Rankin Scale (mRS score) ranged from 0 to 6 is used to measure the recovery of neurological function in patients after stroke. Score 0 means completely no symptom. Score 6 means death. Higher values represent a worse outcome.	24 months
Secondary	Combined events such as stroke, myocardial infarction, and vascular death within 24 months after enrollment	Combined events include stroke, myocardial infarction and vascular death etc; Myocardial infarction occurs when blood stops flowing properly to a part of the heart, and the heart muscle is injured because it is not receiving enough oxygen; vascular death means the death is due to vessel rupture or clot.	24 months
Secondary	Any stroke (ischemic or hemorrhage stroke) inside of the territory of the target artery or all-cause deaths within 36 months after enrollment	Rat of any stroke (ischemic or hemorrhage stroke) inside of the territory of the target artery or all-cause deaths within 36 months after enrollment.	36 months
Secondary	Any stroke (ischemic or hemorrhage stroke) outside of the territory of the target artery within 36 months after enrollment	Rat of any stroke (ischemic or hemorrhage stroke) outside of the territory of the target artery or all-cause deaths within 36 months after enrollment.	36 months
Secondary	Neurological improvement assessed by mRS at 36 months	Modified Rankin Scale (mRS score) ranged from 0 to 6 is used to measure the recovery of neurological function in patients after stroke. Score 0 means completely no symptom. Score 6 means death. Higher values represent a worse outcome.	36 months
Secondary	Combined events such as stroke, myocardial infarction, and vascular death within 36 months after enrollment	Combined events include stroke, myocardial infarction and vascular death etc; Myocardial infarction occurs when blood stops flowing properly to a part of the heart, and the heart muscle is injured because it is not receiving enough oxygen; vascular death means the death is due to vessel rupture or clot.	36 months