Clopidogrel With Aspirin in High-risk Patients With Acute Non-disabling Cerebrovascular Events II

Stroke Clinical Trial

— CHANCE-2  

Official title:

Clopidogrel With Aspirin in High-risk Patients With Acute Non-disabling Cerebrovascular Events II

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04078737
• Other study ID #: 2017ZX09304018001
• Status: Completed
• Phase: Phase 3
• Start date: September 23, 2019
• Est. completion date: July 1, 2021

Study information

• Verified date: November 2021
• Source: Beijing Tiantan Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this trial is to assess the effects of ticagrelor plus aspirin versus clopidogrel plus aspirin on reducing the 3-month risk of any stroke (both ischemic and hemorrhagic, primary outcome) when initiated within 24 hours of symptom onset in CYP2Y19 LOF alleles carriers with TIA or minor stroke.

Description:

According to the Global Burden of Disease(GBD) Study 2016, China bears the greatest lifetime risk of stroke from 25-year-age onward. Minor ischemic events, including minor stroke and TIA, were major parts of stroke manifestations. Events (CHANCE) has shown that 21-day dual antiplatelet therapy (clopidogrel and aspirin) compared to aspirin alone which initiated within 24 hours after symptoms onset would reduce 32% risk of stroke recurrence within 90 day, but not in carriers of CYP2C19 loss-of-function (LOF) alleles. The primary purpose of this study is to compare ticagrelor plus aspirin with clopidogrel plus aspirin on reducing the 3-month risk of any stroke (both ischemic and hemorrhagic, primary outcome) when initiated within 24 hours of symptom onset in CYP2Y19 LOF alleles carriers with TIA or minor stroke. Both intent analysis (ITT) and compliance program set (PPS) were used for analysis. We will use Kaplan-Meier estimates of the cumulative risk of stroke (ischemic or hemorrhagic) event during maximum 90-day follow-up, with hazards ratios and 95% CI calculated using Cox proportional hazards methods and the log-rank test to evaluate the treatment effect. All statistics will be 2-sided with P<0.05 considered significant, accounting for interim analyses. All patients who received study drugs and with at least one safety follow-up record will be included in the safety population. The data for safety evaluation included adverse reactions observed during the trial and changes in laboratory data before and after treatment.

Other known NCT identifiers

• NCT04952311

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6412
• Est. completion date: July 1, 2021
• Est. primary completion date: June 24, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria

1. 40 years or older than 40 years;

2. Acute cerebral ischemic event due to:

• Acute non-disabling ischemic stroke (NIHSS=3 at the time of randomization)or,
• TIA with moderate-to-high risk of stroke (ABCD2 score = 4 at the time of randomization);

3. Can be treated with study drug within 24 hours of symptoms onset*(*Symptom onset is defined by the "last seen normal" principle);

4. CYP2C19 loss-of-function allele carriers;

5. Informed consent signed. Exclusion Criteria

1. Malformation, tumor, abscess or other major non-ischemic brain disease (e.g., multiple sclerosis) on baseline head CT or MRI.

2. Isolated or pure sensory symptoms (e.g., numbness), isolated visual changes, or isolated dizziness/vertigo without evidence of acute infarction on baseline head CT or MRI.

3. Iatrogenic causes (angioplasty or surgery) of minor stroke or TIA.

4. Preceding moderate or severe dependency (modified Rankin scale [mRS] score 3-5).

5. Contraindication to clopidogrel, ticagrelor or aspirin

• Known allergy
• Severe renal (creatinine exceeding 1.5 times of the upper limit of normal range) or hepatic (ALT or AST > twice the upper limit of normal range) insufficiency
• Severe cardiac failure (NYHA level: III to IV)
• History of hemostatic disorder or systemic bleeding
• History of thrombocytopenia or neutropenia
• History of drug-induced hematologic disorder or hepatic dysfunction
• Low white blood cell (<2×109/L) or platelet count (<100×109/L)

6. Hematocrit (HCT) <30%

7. Clear indication for anticoagulation (presumed cardiac source of embolus, e.g., atrial fibrillation, prosthetic cardiac valves known or suspected endocarditis)

8. History of intracranial hemorrhage or amyloid angiopathy

9. History of aneurysm (including intracranial aneurysm and peripheral aneurysm)

10. History of asthma or COPD (chronic obstructive pulmonary disease)

11. High-risk for bradyarrhythmia (first-degree or second-degree AV block caused by sinus node disease, and brady-arrhythmic syncope without pacemaker)

12. History of hyperuricemia nephropathy

13. Anticipated requirement for long-term (>7 days) non-steroidal anti-inflammatory drugs (NSAIDs)

14. Planned or likely revascularization (any angioplasty or vascular surgery) within the next 3 months

15. Scheduled for surgery or interventional treatment requiring study drug cessation

16. Severe non-cardiovascular comorbidity with life expectancy < 3 months

17. Inability to understand and/or follow research procedures due to mental, cognitive, or emotional disorders

18. Dual antiplatelet treatment (or more than two antiplatelet agents) in 72 hours before randomization

19. Current treatment (last dose given within 10 days before randomization) with heparin therapy or oral anti coagulation

20. Intravenous thrombolytic therapy (such as intravenous rtPA) or mechanical thrombectomy within 24 hours prior to randomization

21. Gastrointestinal bleed within 3 months or major surgery within 30 days

22. Diagnosis or suspicious diagnosis of acute coronary syndrome

23. Participation in another clinical study with an experimental product during the last 30 days

24. Currently receiving an experimental drug or device

25. Pregnant, currently trying to become pregnant, or of child-bearing potential and not using birth control

Related Conditions & MeSH terms

• Ischemic Attack, Transient
• Stroke
• Transient Ischemic Attack

Intervention

Drug:
• Ticagrelor and Aspirin
Day of randomization: Day1:Ticagrelor 180mg; placebo of clopidogrel 300mg; aspirin 75-300mg (open label) Day2-21st: Ticagrelor 90mg bid/day; placebo of clopidogrel 75mg; aspirin 75mg (open label) Day 22nd-3 months:Ticagrelor 90mg bid/day; placebo of clopidogrel 75mg
• Clopidogrel and Aspirin
Day of randomization: Day 1: Clopidogrel 300mg; placebo of ticagrelor 180mg; aspirin 75-300mg (open label) Day2-21st: Clopidogrel 75mg/day; placebo of ticagrelor 90mg bid/day; aspirin 75mg (open label) Day 22nd-3 months:Clopidogrel 75mg; placebo of ticagrelor 90mg bid/day

Locations

Country	Name	City	State
China	Anqing Municipal Hospital	Anqing	Anhui
China	Anyang People's Hospital	Anyang	Henan
China	Affiliated Hospital of Hebei Medical University	Baoding	Hebei
China	Affiliated Hospital of Hebei University	Baoding	Hebei
China	Baoji High-tech People's Hospital	Baoji	Shaanxi
China	Baotou CentralHospital	Baotou	Inner Mongolia Autonomous Region
China	The first Affiliated Hospital of Baotou Medical College	Baotou	Inner Mongolia Autonomous Region
China	The second Affiliated Hospital of Baotou Medical College	Baotou	Inner Mongolia Autonomous Region
China	Wuyuan County People's Hospital	Bayan Nur	Inner Mongolia Autonomous Region
China	Beijing Chaoyang Hospital, Capital MedicalUniversity(west Hospital)	Beijing	Beijing
China	Beijing Coal Group Hospital	Beijing	Beijing
China	Beijing Shunyi Airport Hospital	Beijing	Beijing
China	Beijing Tian tan Hospital	Beijing	Beijing
China	Peking University Third Hospital	Beijing	Beijing
China	The First Hospital of Fangshan District	Beijing	Beijing
China	The First Affiliated Hospital of Bengbu Medical College	Bengbu	Anhui
China	Hulun Buir People's Hospital	Buri	Inner Mongolia Autonomous Region
China	Jilin Provincial People's Hospital	Changchun	Jilin
China	Sino-Japanese Friendship Hospital Of Jilin University	Changchun	Jilin
China	The First Hospital Of Jilin University	Changchun	Jilin
China	Changge People's Hospital	Changge	Henan
China	First hospital of Changsha city	Changsha	Hunan
China	Changzhi People's Hospital	Changzhi	Shanxi
China	Heping Hospital affiliated to Changzhi Medical College	Changzhi	Shanxi
China	The Affiliated Hospital of Chengde Medical College	Chengde	Hebei
China	West China Hospital Of Sichuan University	Chengdou	Sichuan
China	Chengdu second Municipal People'sHospital	Chengdu	Sichuan
China	Sichuan Provincial People's Hospital	Chengdu	Sichuan
China	Chenzhou First People's Hospital	Chenzhou	Hunan
China	Fourth People's Hospital of Chenzhou	Chenzhou	Hunan
China	Affiliated Hospital of Chifeng University	Chifeng	Inner Mongolia Autonomous Region
China	Chifeng City Hospital	Chifeng	Inner Mongolia Autonomous Region
China	Chongqing Fifth People's Hospital	Chongqing	Chongqing
China	Chongqing Fuling Central Hospital	Chongqing	Chongqing
China	Chongqing Kaizhou District People's Hospital	Chongqing	Chongqing
China	Chongqing Nanchuan District People's Hospital	Chongqing	Chongqing
China	Chongqing People's Hospital	Chongqing	Chongqing
China	Chongqing Sanbo Chang 'an Hospital	Chongqing	Chongqing
China	Chongqing Three Gorges Central Hospital	Chongqing	Chongqing
China	Daping Hospital of Army Military Medical University	Chongqing	Chongqing
China	People's Hospital of Rongchang District, Chongqing,	Chongqing	Chongqing
China	The First Affiliated Hospital of Chongqing Medical University	Chongqing	Chongqing
China	The Second Affiliated Hospital of Chongqing Medical University	Chongqing	Chongqing
China	The Third Affiliated Hospital of Chongqing Medical University	Chongqing	Chongqing
China	Xiushan Tujia and Miao Autonomous County People's Hospital	Chongqing	Chongqing
China	Xinhua Hospital affiliated to Dalian University	Dalian	Liaoning
China	Hainan West Central Hospital	Danzhou	Hainan
China	Daqing Oilfield Gengeal Hospital	Daqing	Heilongjiang
China	Daqing People's Hospital	Daqing	Heilongjiang
China	Datong Fifth People's Hospital	Datong	Shanxi
China	The Third People's Hospital of Datong	Datong	Shanxi
China	dazhou Central Hospital	Dazhou	Sichuan
China	Dezhou People's Hospital	Dezhou	Shandong
China	Ningjin County People's Hospital	Dezhou	Shandong
China	Dongguan People's Hospital	Dongguan	Guangdong
China	Fuzhou Second Hospital	Fuzhou	Fujian
China	The Third Affiliated Hospital of Fujian University of Traditional Chinese Medicine	Fuzhou	Fujian
China	Ganzhou city people's Hospital	Ganzhou	Jiangxi
China	Nanfang Hospital Of Southern Medical University	Guangzhou	Guangdong
China	The First Affiliated Hospital of Jinan University	Guangzhou	Guangdong
China	The Second Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong
China	Affiliated Hospital of Guizhou Medical University	Guiyang	Guizhou
China	First Affiliated Hospital of Xinjiang Medical University	Guiyang	Xinjiang Autonomous Region
China	Guiyang Second People's Hospital	Guiyang	Guizhou
China	Guyuan people's hospital	Guyuan	Ningxia Hui Autonomous Region
China	The First Affiliated Hospital of Hainan Medical University	Haikou	Hainan
China	Hangzhou first people's Hospital	Hangzhou	Zhejiang
China	The First Hospital of Harbin Medical University	Harbin	Heilongjiang
China	The Second Hospital of Harbin Medical University(Department of Neurology ward )	Harbin	Heilongjiang
China	The Second Hospital of Harbin Medical University(Department of Neurology ward 1)	Harbin	Heilongjiang
China	Hejian People's Hospital	Hejian	Hebei
China	HaLixun InternationalPeace Hospital	Hengshui	Hebei
China	Hengshui fourth People Hospital(Department of Neurology ward 2)	Hengshui	Hebei
China	The Fourth People's Hospital of Hengshui City(Department of Neurology ward 1)	Hengshui	Hebei
China	The First Affiliated Hospital of Nanhua University	Hengyang	Hunan
China	Inner Mongolia International Mongolian Hospital	Hohhot	Inner Mongolia Autonomous Region
China	Inner Mongolia People's Hospital	Hohhot	Inner Mongolia Autonomous Region
China	Huaian Hospital of Traditional Chinese Medicine	Huai'an	Jiangsu
China	Lianshui County People's Hospital	Huai'an	Jiangsu
China	Second People's Hospital of Huludao City	Huludao	Liaoning
China	The First Affiliated Hospital of Jiamusi University	Jiamusi	Heilongjiang
China	Xiuwu County People's Hospital	Jiaozuo	Henan
China	Shandong Provincial Hospital	Jinan	Shandong
China	The First People's Hospital of Jingdehzne City	Jingdezhen	Jiangxi
China	Affiliated Hospital of Jiujiang College	Jiujiang	Jiangxi
China	Jiujiang first people's Hospital	Jiujiang	Jiangxi
China	Jiyuan People's Hospital	Jiyuan	Henan
China	Kaifeng Central Hospital	Kaifeng	Henan
China	weishi county Central Hospital	Kaifeng	Henan
China	First People's Hospital of Yunnan Province	Kunming	Yunnan
China	The Second People's Hospital of Lianyungang	Lianyungang	Jiangsu
China	Dongchangfu people's Hospital	Liaocheng	Shandong
China	Guanxian People's Hospital	LiaoCheng	Shandong
China	Liaocheng Central Hospital	Liaocheng	Shandong
China	Liaocheng City Second People's Hospital	Liaocheng	Shandong
China	Liaocheng City Third People's Hospital	Liaocheng	Shandong
China	Liaocheng People's Hospital	Liaocheng	Shandong
China	Liaocheng Veterans Hospital	Liaocheng	Shandong
China	The Brain Hospital of Liaocheng People's Hospital	Liaocheng	Shandong
China	Linqing People's Hospital	Linqing	Shandong
China	lishui municipal Central Hospital	Lishui	Zhejiang
China	Loudi City Central Hospital	Loudi	Hunan
China	Luohe Central Hospital	Luohe	Henan
China	Luoyang Central Hospital	Luoyang	Henan
China	Luoyang New District People's Hospital	Luoyang	Henan
China	The first Affiliated Hospital of Henan University of Science and Technology	Luoyang	Henan
China	The Second Affiliated Hospital of Henan University of Science and Technology	Luoyang	Henan
China	Hongqi Hospital affiliated to Mudanjiang Medical University	Mudanjiang	Heilongjiang
China	First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	Jiangxi Provincial People's Hospital	Nanchang	Jiangxi
China	BenQ Hospital affiliated to Nanjing Medical University	Nanjing	Jiangsu
China	Jiangsu Provincial Hospital of Traditional Chinese Medicine	Nanjing	Jiangsu
China	Nanjing Brain Hospital	Nanjing	Jiangsu
China	Nanjing Gaochun People's Hospital	Nanjing	Jiangsu
China	Nanjing Gulou Hospital	Nanjing	Jiangsu
China	Nanjing Jiangbei People's Hospital	Nanjing	Jiangsu
China	Nanjing Jiangning Hospital	Nanjing	Jiangsu
China	The Fourth Affiliated Hospital of Nanjing Medical University	Nanjing	Jiangsu
China	The Second Affiliated Hospital of Nanjing Medical University	Nanjing	Jiangsu
China	Affiliated Hospital of Nantong University	Nantong	Jiangsu
China	Hai 'an People's Hospital	Nantong	Jiangsu
China	Nantong 6th People's Hospital	Nantong	Jiangsu
China	Nantong First People's Hospital	Nantong	Jiangsu
China	Nantong Fourth People's Hospital	Nantong	Jiangsu
China	Nantong Hospital of Traditional Chinese Medicine	Nantong	Jiangsu
China	Nantong Second People's Hospital	Nantong	Jiangsu
China	Nantong Third People's Hospital	Nantong	Jiangsu
China	Rudong County People's Hospital	Nantong	Jiangsu
China	Rugao People's Hospital	Nantong	Jiangsu
China	The Third People's Hospital in Tongzhou District, Nantong	Nantong	Jiangsu
China	Tongzhou District 8th People's Hospital of Nantong City	Nantong	Jiangsu
China	Tongzhou District People's Hospital of Nantong City	Nantong	Jiangsu
China	Pingdingshan First People's Hospital	Pingdingshan	Henan
China	Affiliated Hospital of Qingdao University Medical College	Qingdao	Shandong
China	Qingdao Municipal Hospital	Qingdao	Shandong
China	Qingdao West Coast New Area People's Hospital	Qingdao	Shandong
China	Qiqihar Rongjian Institute of Stroke Prevention and Treatment	Qiqihar	Heilongjiang
China	Zhejiang Wenzhou Medical College Third Affiliated Hospital	Ruian	Zhejiang
China	Sanmenxia Central Hospital	Sanmenxia	Henan
China	Sanming First Hospital Affiliated to Fujian Medical University	Sanming	Fujian
China	Putuo District Central Hospital	Shanghai	Shanghai
China	Shanghai 7th People's Hospital	Shanghai	Shanghai
China	Shangqiu Fourth People's Hospital	Shangqiu	Henan
China	Suixian county Hospital of Traditional Chinese Medicine	Shangqiu	Henan
China	Shangrao City People's Hospital	Shangrao	Jiang XI
China	The first Affiliated Hospital of Shantou University Medical College	Shantou	Guangdong
China	shaoyang Central Hospital	Shaoyang	Hunan
China	First People's Hospital of Shenyang	Shenyang	Liaoning
China	Shengjing Hospital of China Medical University	Shenyang	Liaoning
China	Huazhong University of Science and Technology Union Shenzhen Hospital	Shenzhen	Shenzhen
China	Shenzhen Integrated Chinese and Western Medicine Hospital	Shenzhen	Shenzhen
China	Shenzhen Luohu People's Hospital	Shenzhen	Shenzhen
China	Shenzhen Second People's Hospital	Shenzhen	Shenzhen
China	The Second Hospitalof Hebei Medical University	Shijiazhuang	Hebei
China	Second people's Hospital of shizuishan	Shizuishan	Ningxia Hui Autonomous Region
China	Shizuishan First People's Hospital	Shizuishan	Ningxia Hui Autonomous Region
China	The Fifth People's Hospital of Ningxia Hui Autonomous Region	Shizuishan	Ningxia Hui Autonomous Region
China	The Second People's Hospital of Shizuishan	Shizuishan	Ningxia Hui Autonomous Region
China	Siyang County People's Hospital	Suqian	Jiangsu
China	Siyang Kangda Hospital	Suqian	Jiangsu
China	Suqian People's Hospital	Suqian	Jiangsu
China	Suzhou Municipal Hospital	Suzhou	Jiangsu
China	The Second Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	Shanxi Bethune Hospital	Taiyuan	Shanxi
China	Shanxi cardiovascular disease hospital	Taiyuan	Shanxi
China	Taiyuan Iron and Steel (Group) Co, Ltd,General Hospital	Taiyuan	Shanxi
China	The First Hospital of Shanxi Medical University	Taiyuan	Shanxi
China	Taizhou First People's Hospital	Taizhou	Zhejiang
China	Taizhou People's Hospital	Taizhou	Jiangsu
China	Xinghua People's Hospital	Taizhou	Jiangsu
China	Tianjin Medical University General Hospital	Tianjin	Tianjin
China	People's Hospital Of Xinjiang Uygur Autonomous Region	Urumqi	Xinjiang Autonomous Region
China	Affiliated Hospital of Weifang Medical University	Weifang	Shandong
China	Sunshine Union Hospital	Weifang	Shandong
China	weihai Central Hospital	Weihai	Shandong
China	Wendeng District People's Hospital	Weihai	Shandong
China	weinan Central Hospital	Weinan	Shaanxi
China	The Central Hospital of Wuhan	Wuhan	Hubei
China	Wuhan No.1 Hospital	Wuhan	Hubei
China	Wuwei People's Hospital	Wuwei	Gansu
China	Affiliated Hospital of Jiangnan University	Wuxi	Jiangsu
China	Jiangyin People's Hospital	Wuxi	Jiangsu
China	Wuxi People's Hospital	Wuxi	Jiangsu
China	Yixing People's Hospital	Wuxi	Jiangsu
China	Xi 'an Fengcheng Hospital	Xi'an	Shaanxi
China	Xi 'an First Hospital	Xi'an	Shanxi
China	Xi 'an Hi-tech Hospital	Xi'an	Shaanxi
China	Xian 141 Hospital	Xi'an	Shaanxi
China	Xiangtan Central Hospital	Xiangtan	Hunan
China	Xingyang People's Hospital	Xingyang	Henan
China	The first Affiliated Hospital of Xinxiang Medical University	Xinxiang	Henan
China	Affiliated Hospital of Xuzhou Medical University(Department of Neurology ward 1)	Xuzhou	Jiangsu
China	Affiliated Hospital of Xuzhou Medical University(Department of Neurology ward 2)	Xuzhou	Jiangsu
China	xuzhou Central Hospital	Xuzhou	Jiangsu
China	Xuzhou coal mining group General Hospital	Xuzhou	Jiangsu
China	Affiliated Hospital of Yangzhou University	Yangzhou	Jiangsu
China	Subei People's Hospital of Jiangsu province	Yangzhou	Jiangsu
China	Penglai People's Hospital	Yantai	Shandong
China	Yantai Beihai Hospita	Yantai	Shandong
China	Cardiovascular and Cerebrovoscular Hospital of General Hospital of Ningxia Med. Univ	Yinchuan	Ningxia Hui Autonomous Region
China	General Hospital of Ningxia Medical University	Yinchuan	Ningxia Hui Autonomous Region
China	People's Hospital of Ningxia Hui Autonomous Region	Yinchuan	Ningxia Hui Autonomous Region
China	Yinchuan First People's Hospital	Yinchuan	Ningxia Hui Autonomous Region
China	Friendship Hospital of Ili Kazak Autonomous Prefecture	Yining	Xinjiang Autonomous Region
China	Yueyang Second People's Hospital	Yueyang	Hunan
China	The First Affiliated Hospital of Hebei North University	Zhangjiakou	Hebei
China	Zhangye People's Hospital Affiliated to Hexi College	Zhangye	Gansu
China	Gongyi People's Hospital	Zhengzhou	Henan
China	The First Affiliated Hospital of Henan University of Traditional Chinese Medicine	Zhengzhou	Henan
China	The fourth peoples hospital of zhenjiang city	Zhenjiang	Jiangsu
China	Zhongwei People's Hospital	Zhongwei	Ningxia Hui Autonomous Region
China	Zhoukou Yongshan Hospital	Zhoukou	Henan
China	Zhumadian Hospital of Traditional Chinese Medicine	Zhumadian	Henan
China	Second Central Hospital of Baoding	Zhuozhou	Hebei

Sponsors (2)

Lead Sponsor	Collaborator
Beijing Tiantan Hospital	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
Other	Moderate and severe bleeding events according to the GUSTO criteria	Severe bleeding incidence (GUSTO definition), including fatal bleeding and symptomatic intracranial hemorrhage.	3 months after randomization
Other	Moderate and severe bleeding events according to the GUSTO criteria	Severe bleeding incidence (GUSTO definition), including fatal bleeding and symptomatic intracranial hemorrhage.	1 year after randomization
Other	All bleeding events	All bleeding events (severe/moderate bleeding and intracranial hemorrhage)	3 months and 1 year after randomization
Other	Total mortality	Total mortality	3 months and 1 year after randomization
Other	Incidence symptomatic intracranial hemorrhagic events	Incidence symptomatic intracranial hemorrhagic events	3 months and 1 year after randomization
Other	Adverse events	Adverse events	3 months and 1 year after randomization
Primary	Any new stroke events (ischemic stroke or hemorrhagic stroke) within 3 months	The aim is to assess the effects of ticagrelor plus aspirin versus clopidogrel plus aspirin on reducing the 3-month risk of any stroke (both ischemic and hemorrhagic, primary outcome) when initiated within 24 hours of symptom onset in CYP2Y19 LOF alleles carriers with TIA or minor stroke.	3 months after randomization
Secondary	Any new stroke events within 30 days and 1 year	Percentage of patients with the 30 days and 1 year new stroke events (ischemic stroke/ hemorrhagic stroke) as a cluster and evaluated individually.	30 days and 1 year after randomization
Secondary	New clinical vascular events including stroke, TIA, myocardial infarction, and vascular deaths within 3 months and 1 year	Percentage of patients with the 3 months and 1 year new clinical vascular events (ischemic stroke/ hemorrhagic stroke/ TIA/ myocardial infarction/vascular death)	3 months and 1 year after randomization
Secondary	New ischemic stroke within 3 months and 1 year	Percentage of patients with the 3 months and 1 year new ischemic stroke will be evaluated.	3 months and 1 year after randomization
Secondary	Disabling stroke (Modified Rankin Scale score, mRS>1) at 3 months and 1 year	Modified Rankin Scale, a commonly used scale for measuring the degree of dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. 0 - No symptoms.1 - No significant disability. Able to carry out all usual activities, despite some symptoms.2 - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.3 - Moderate disability. Requires some help, but able to walk unassisted.4 - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.5 - Severe disability. Requires constant nursing care and attention, bedridden, incontinent.6 - Dead. The mRS scores between 3 to 6 points are considered to be poor functional outcome. (dead).	3 months and 1 year after randomization
Secondary	Incidence and severity of recurrent stroke and TIA during follow-up to 3 months and 1-year	(Severity is measured using a six-level ordered categorical scale that incorporates the mRS: fatal stroke/severe non-fatal stroke [mRS 4 or 5]/moderate stroke [mRS 2 or 3]/mild stroke [mRS 0 or 1]/TIA/no stroke-TIA).	3 months and 1 year after randomization
Secondary	Neurological impairment at 3 months (NIHSS increased=4 from baseline)	The National Institutes of Health Stroke Scale (NIHSS) score classifies neurologic deficit from 0 (no deficit) to 42 (most severe).	3 months after randomization
Secondary	Quality of Life (EuroQol EQ-5D scale) at 3 months and at 1 year	Further efficacy exploratory analysis:Quality of Life (EuroQol EQ-5D scale). We will use the EQ-5D-5L scale to evaluate the quality of life. EQ-5D-5L is a standardized instrument for measuring generic health status. It has been widely used in population health surveys, clinical studies, economic evaluation and in routine outcome measurement in the delivery of operational healthcare. The EQ-5D-5L has five domain scales (mobility, self-care, usual activities, pain and discomfort, and anxiety and depression) and five levels for each domain.	3 months and 1 year after randomization
Secondary	Stratified analysis	The influence on treatment effect of age, gender, Body Mass Index (BMI), index event type (TIA vs. minor stroke), time from index event to randomization, etiology subtype, diabetes mellitus, hypertension, type of LOF allele, previous ischemic stroke or TIA, prior antiplatelet therapy, prior statin therapy, prior smoking status, and symptomatic intracranial and extracranial artery stenosis will be evaluated in subgroup analyses.	3 months and 1 year after randomization