Clopidogrel With Aspirin in High-risk Patients With Acute Non-disabling Cerebrovascular Events II (CHANCE-2)

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.

Study Overview

• Status: Completed
• Conditions: Stroke; Transient Ischemic Attack
• Intervention / Treatment: Drug: Ticagrelor and Aspirin; Drug: Clopidogrel and Aspirin

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 6412
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Anqing, Anhui, China, 246003
      • Anqing Municipal Hospital
    • Bengbu, Anhui, China, 233004
      • The First Affiliated Hospital of Bengbu Medical College
  • Beijing
    • Beijing, Beijing, China
      • Peking University Third Hospital
    • Beijing, Beijing, China, 100043
      • Beijing Chaoyang Hospital, Capital MedicalUniversity（west Hospital）
    • Beijing, Beijing, China, 100070
      • Beijing Tian tan Hospital
    • Beijing, Beijing, China, 101318
      • Beijing Shunyi Airport Hospital
    • Beijing, Beijing, China, 102488
      • The First Hospital of Fangshan District
    • Beijing, Beijing, China
      • Beijing Coal Group Hospital
  • Chongqing
    • Chongqing, Chongqing, China, 400010
      • The Second Affiliated Hospital of Chongqing Medical University
    • Chongqing, Chongqing, China, 404000
      • Chongqing Three Gorges Central Hospital
    • Chongqing, Chongqing, China, 400010
      • Chongqing People's Hospital
    • Chongqing, Chongqing, China, 400023
      • Chongqing Sanbo Chang 'an Hospital
    • Chongqing, Chongqing, China, 400042
      • Daping Hospital of Army Military Medical University
    • Chongqing, Chongqing, China, 400060
      • The First Affiliated Hospital of Chongqing Medical University
    • Chongqing, Chongqing, China, 400062
      • Chongqing Fifth People's Hospital
    • Chongqing, Chongqing, China, 401120
      • The Third Affiliated Hospital of Chongqing Medical University
    • Chongqing, Chongqing, China, 402460
      • People's Hospital of Rongchang District, Chongqing,
    • Chongqing, Chongqing, China, 405400
      • Chongqing Kaizhou District People's Hospital
    • Chongqing, Chongqing, China, 408000
      • Chongqing Fuling Central Hospital
    • Chongqing, Chongqing, China, 408400
      • Chongqing Nanchuan District People's Hospital
    • Chongqing, Chongqing, China, 409900
      • Xiushan Tujia and Miao Autonomous County People's Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350025
      • The Third Affiliated Hospital of Fujian University of Traditional Chinese Medicine
    • Fuzhou, Fujian, China
      • Fuzhou Second Hospital
    • Sanming, Fujian, China, 100043
      • Sanming First Hospital Affiliated to Fujian Medical University
  • Gansu
    • Wuwei, Gansu, China, 733000
      • Wuwei People's Hospital
    • Zhangye, Gansu, China, 734000
      • Zhangye People's Hospital Affiliated to Hexi College
  • Guangdong
    • Dongguan, Guangdong, China, 523000
      • Dongguan People's Hospital
    • Guangzhou, Guangdong, China, 510260
      • The Second Affiliated Hospital of Guangzhou Medical University
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital of Southern Medical University
    • Guangzhou, Guangdong, China, 510632
      • The First Affiliated Hospital of Jinan University
    • Shantou, Guangdong, China, 515041
      • The First Affiliated Hospital of Shantou University Medical College
  • Guizhou
    • Guiyang, Guizhou, China, 550000
      • Guiyang Second People's Hospital
    • Guiyang, Guizhou, China, 550004
      • Affiliated Hospital of Guizhou Medical University
  • Hainan
    • Danzhou, Hainan, China, 571799
      • Hainan West Central Hospital
    • Haikou, Hainan, China, 570102
      • The First Affiliated Hospital of Hainan Medical University
  • Hebei
    • Baoding, Hebei, China, 071000
      • Affiliated Hospital of Hebei Medical University
    • Baoding, Hebei, China, 071000
      • Affiliated Hospital of Hebei University
    • Chengde, Hebei, China, 067000
      • The Affiliated Hospital of Chengde Medical College
    • Hejian, Hebei, China, 062450
      • Hejian People's Hospital
    • Hengshui, Hebei, China, 053000
      • HaLixun InternationalPeace Hospital
    • Hengshui, Hebei, China, 053000
      • Hengshui fourth People Hospital（Department of Neurology ward 2）
    • Hengshui, Hebei, China, 053000
      • The Fourth People's Hospital of Hengshui City（Department of Neurology ward 1）
    • Shijiazhuang, Hebei, China, 050000
      • The Second Hospitalof Hebei Medical University
    • Zhangjiakou, Hebei, China, 75000
      • The First Affiliated Hospital of Hebei North University
    • Zhuozhou, Hebei, China, 072750
      • Second Central Hospital of Baoding
  • Heilongjiang
    • Daqing, Heilongjiang, China, 163001
      • Daqing Oilfield Gengeal Hospital
    • Daqing, Heilongjiang, China, 163361
      • Daqing People's Hospital
    • Harbin, Heilongjiang, China, 150001
      • The First Hospital of Harbin Medical University
    • Harbin, Heilongjiang, China, 150086
      • The Second Hospital of Harbin Medical University（Department of Neurology ward 1）
    • Harbin, Heilongjiang, China, 150086
      • The Second Hospital of Harbin Medical University（Department of Neurology ward ）
    • Jiamusi, Heilongjiang, China, 154002
      • The First Affiliated Hospital of Jiamusi University
    • Mudanjiang, Heilongjiang, China, 157000
      • Hongqi Hospital Affiliated to Mudanjiang Medical University
    • Qiqihar, Heilongjiang, China
      • Qiqihar Rongjian Institute of Stroke Prevention and Treatment
  • Henan
    • Anyang, Henan, China, 455000
      • Anyang People's Hospital
    • Changge, Henan, China, 461500
      • Changge People's Hospital
    • Jiaozuo, Henan, China, 454350
      • Xiuwu County People's Hospital
    • Jiyuan, Henan, China, 459000
      • Jiyuan People's Hospital
    • Kaifeng, Henan, China, 475000
      • Kaifeng Central Hospital
    • Kaifeng, Henan, China, 475500
      • Weishi County Central Hospital
    • Luohe, Henan, China, 462000
      • Luohe Central Hospital
    • Luoyang, Henan, China, 471000
      • Luoyang Central Hospital
    • Luoyang, Henan, China, 471000
      • The First Affiliated Hospital of Henan University of Science And Technology
    • Luoyang, Henan, China, 471000
      • The Second Affiliated Hospital of Henan University of Science and Technology
    • Luoyang, Henan, China, 471023
      • Luoyang New District People's Hospital
    • Pingdingshan, Henan, China, 467000
      • Pingdingshan First People's Hospital
    • Sanmenxia, Henan, China, 472000
      • Sanmenxia Central Hospital
    • Shangqiu, Henan, China, 476000
      • Shangqiu Fourth People's Hospital
    • Shangqiu, Henan, China, 476900
      • Suixian County Hospital of Traditional Chinese Medicine
    • Xingyang, Henan, China, 450100
      • Xingyang People's Hospital
    • Xinxiang, Henan, China, 453100
      • The First Affiliated Hospital of Xinxiang Medical University
    • Zhengzhou, Henan, China, 450000
      • The First Affiliated Hospital of Henan University of Traditional Chinese Medicine
    • Zhengzhou, Henan, China, 451200
      • Gongyi People's Hospital
    • Zhoukou, Henan, China, 461300
      • Zhoukou Yongshan Hospital
    • Zhumadian, Henan, China, 463000
      • Zhumadian Hospital of Traditional Chinese Medicine
  • Hubei
    • Wuhan, Hubei, China, 430014
      • The Central Hospital of Wuhan
    • Wuhan, Hubei, China, 430000
      • Wuhan No.1 Hospital
  • Hunan
    • Changsha, Hunan, China, 410005
      • First hospital of Changsha city
    • Chenzhou, Hunan, China, 423000
      • Chenzhou First People's Hospital
    • Chenzhou, Hunan, China, 423000
      • Fourth People's Hospital of Chenzhou
    • Hengyang, Hunan, China, 421001
      • The First Affiliated Hospital of Nanhua University
    • Loudi, Hunan, China, 417000
      • Loudi City Central Hospital
    • Shaoyang, Hunan, China
      • Shaoyang Central Hospital
    • Xiangtan, Hunan, China, 411100
      • Xiangtan Central Hospital
    • Yueyang, Hunan, China, 414000
      • Yueyang Second People's Hospital
  • Inner Mongolia Autonomous Region
    • Baotou, Inner Mongolia Autonomous Region, China, 014010
      • The First Affiliated Hospital of Baotou Medical College
    • Baotou, Inner Mongolia Autonomous Region, China, 014040
      • Baotou CentralHospital
    • Baotou, Inner Mongolia Autonomous Region, China, 14030
      • The Second Affiliated Hospital of Baotou Medical College
    • Bayan Nur, Inner Mongolia Autonomous Region, China, 15100
      • Wuyuan County People's Hospital
    • Buri, Inner Mongolia Autonomous Region, China, 21000
      • Hulun Buir People's Hospital
    • Chifeng, Inner Mongolia Autonomous Region, China, 024000
      • Chifeng City Hospital
    • Chifeng, Inner Mongolia Autonomous Region, China, 024005
      • Affiliated Hospital of Chifeng University
    • Hohhot, Inner Mongolia Autonomous Region, China, 010017
      • Inner Mongolia People's Hospital
    • Hohhot, Inner Mongolia Autonomous Region, China, 010069
      • Inner Mongolia International Mongolian Hospital
  • Jiang XI
    • Shangrao, Jiang XI, China
      • Shangrao City People's Hospital
  • Jiangsu
    • Huai'an, Jiangsu, China, 223001
      • Huaian Hospital of Traditional Chinese Medicine
    • Huai'an, Jiangsu, China, 223400
      • Lianshui County People's Hospital
    • Lianyungang, Jiangsu, China, 222023
      • The Second People's Hospital of Lianyungang
    • Nanjing, Jiangsu, China, 210029
      • Nanjing Brain Hospital
    • Nanjing, Jiangsu, China, 210003
      • The Second Affiliated Hospital of Nanjing Medical University
    • Nanjing, Jiangsu, China, 210000
      • Nanjing Jiangning Hospital
    • Nanjing, Jiangsu, China, 210008
      • Nanjing Gulou Hospital
    • Nanjing, Jiangsu, China, 210019
      • BenQ Hospital affiliated to Nanjing Medical University
    • Nanjing, Jiangsu, China, 210029
      • Jiangsu Provincial Hospital of Traditional Chinese Medicine
    • Nanjing, Jiangsu, China, 210031
      • The Fourth Affiliated Hospital of Nanjing Medical University
    • Nanjing, Jiangsu, China, 210048
      • Nanjing Jiangbei People's Hospital
    • Nanjing, Jiangsu, China, 211300
      • Nanjing Gaochun People's Hospital
    • Nantong, Jiangsu, China, 226000
      • Nantong 6th People's Hospital
    • Nantong, Jiangsu, China, 226000
      • Nantong Hospital of Traditional Chinese Medicine
    • Nantong, Jiangsu, China, 226000
      • The Third People's Hospital in Tongzhou District, Nantong
    • Nantong, Jiangsu, China, 226001
      • Affiliated Hospital of Nantong University
    • Nantong, Jiangsu, China, 226001
      • Nantong First People's Hospital
    • Nantong, Jiangsu, China, 226002
      • Nantong Second People's Hospital
    • Nantong, Jiangsu, China, 226005
      • Nantong Fourth People's Hospital
    • Nantong, Jiangsu, China, 22600
      • Nantong Third People's Hospital
    • Nantong, Jiangsu, China, 226300
      • Tongzhou District People's Hospital of Nantong City
    • Nantong, Jiangsu, China, 226400
      • Rudong County People's Hospital
    • Nantong, Jiangsu, China, 226500
      • Rugao People's Hospital
    • Nantong, Jiangsu, China, 226600
      • Hai 'an People's Hospital
    • Nantong, Jiangsu, China
      • Tongzhou District 8th People's Hospital of Nantong City
    • Suqian, Jiangsu, China, 223700
      • Siyang County People's Hospital
    • Suqian, Jiangsu, China, 223700
      • Siyang Kangda Hospital
    • Suqian, Jiangsu, China, 223800
      • Suqian People's Hospital
    • Suzhou, Jiangsu, China, 215004
      • The Second Affiliated Hospital of Soochow University
    • Suzhou, Jiangsu, China, 215000
      • Suzhou Municipal Hospital
    • Taizhou, Jiangsu, China, 225300
      • Taizhou People's Hospital
    • Taizhou, Jiangsu, China, 225700
      • Xinghua People's Hospital
    • Wuxi, Jiangsu, China, 214000
      • Wuxi People's Hospital
    • Wuxi, Jiangsu, China, 214041
      • Affiliated Hospital of Jiangnan University
    • Wuxi, Jiangsu, China, 214200
      • Yixing People's Hospital
    • Wuxi, Jiangsu, China, 214400
      • Jiangyin People's Hospital
    • Xuzhou, Jiangsu, China, 221000
      • Xuzhou Central Hospital
    • Xuzhou, Jiangsu, China, 221000
      • Xuzhou coal mining group General Hospital
    • Xuzhou, Jiangsu, China, 221002
      • Affiliated Hospital of Xuzhou Medical University（Department of Neurology ward 1）
    • Xuzhou, Jiangsu, China, 221002
      • Affiliated Hospital of Xuzhou Medical University（Department of Neurology ward 2）
    • Yangzhou, Jiangsu, China, 225009
      • Subei People's Hospital of Jiangsu province
    • Yangzhou, Jiangsu, China, 225012
      • Affiliated Hospital of Yangzhou University
    • Zhenjiang, Jiangsu, China, 212001
      • The fourth peoples hospital of zhenjiang city
  • Jiangxi
    • Ganzhou, Jiangxi, China, 341000
      • Ganzhou City People's Hospital
    • Jingdezhen, Jiangxi, China, 333000
      • The First People's Hospital of Jingdehzne City
    • Jiujiang, Jiangxi, China, 332000
      • Affiliated Hospital of Jiujiang College
    • Jiujiang, Jiangxi, China, 332000
      • Jiujiang First People's Hospital
    • Nanchang, Jiangxi, China, 330006
      • Jiangxi Provincial People's Hospital
    • Nanchang, Jiangxi, China, 330000
      • First Affiliated Hospital of Nanchang University
  • Jilin
    • Changchun, Jilin, China, 130031
      • The First Hospital of Jilin University
    • Changchun, Jilin, China, 130031
      • Sino-Japanese Friendship Hospital Of Jilin University
    • Changchun, Jilin, China
      • Jilin Provincial People's Hospital
  • Liaoning
    • Dalian, Liaoning, China, 116023
      • Xinhua Hospital Affiliated to Dalian University
    • Huludao, Liaoning, China
      • Second People's Hospital of Huludao City
    • Shenyang, Liaoning, China, 110004
      • Shengjing Hospital Of China Medical University
    • Shenyang, Liaoning, China, 110041
      • First People's Hospital of Shenyang
  • Ningxia Hui Autonomous Region
    • Guyuan, Ningxia Hui Autonomous Region, China, 756000
      • Guyuan People's Hospital
    • Shizuishan, Ningxia Hui Autonomous Region, China, 753000
      • The Fifth People's Hospital of Ningxia Hui Autonomous Region
    • Shizuishan, Ningxia Hui Autonomous Region, China, 753000
      • The Second People's Hospital of Shizuishan
    • Shizuishan, Ningxia Hui Autonomous Region, China, 753200
      • Shizuishan First People's Hospital
    • Shizuishan, Ningxia Hui Autonomous Region, China, 753400
      • Second people's Hospital of shizuishan
    • Yinchuan, Ningxia Hui Autonomous Region, China, 750001
      • General Hospital of Ningxia Medical University
    • Yinchuan, Ningxia Hui Autonomous Region, China, 750001
      • Yinchuan First People's Hospital
    • Yinchuan, Ningxia Hui Autonomous Region, China, 750002
      • Cardiovascular and Cerebrovoscular Hospital of General Hospital of Ningxia Med. Univ
    • Yinchuan, Ningxia Hui Autonomous Region, China, 750002
      • People's Hospital of Ningxia Hui Autonomous Region
    • Zhongwei, Ningxia Hui Autonomous Region, China, 755000
      • Zhongwei People's Hospital
  • Shaanxi
    • Baoji, Shaanxi, China, 721000
      • Baoji High-tech People's Hospital
    • Weinan, Shaanxi, China, 714000
      • Weinan Central Hospital
    • Xi'an, Shaanxi, China, 710000
      • Xi 'an Hi-tech Hospital
    • Xi'an, Shaanxi, China, 710016
      • Xi 'an Fengcheng Hospital
    • Xi'an, Shaanxi, China, 710089
      • Xian 141 Hospital
  • Shandong
    • Dezhou, Shandong, China, 2530000
      • Dezhou People's Hospital
    • Dezhou, Shandong, China, 253400
      • Ningjin County People's Hospital
    • Jinan, Shandong, China, 250021
      • Shandong Provincial Hospital
    • LiaoCheng, Shandong, China, 252500
      • Guanxian People's Hospital
    • Liaocheng, Shandong, China, 252000
      • Liaocheng City Third People's Hospital
    • Liaocheng, Shandong, China, 252000
      • Liaocheng People's Hospital
    • Liaocheng, Shandong, China, 252000
      • Liaocheng Veterans Hospital
    • Liaocheng, Shandong, China, 252000
      • The Brain Hospital of Liaocheng People's Hospital
    • Liaocheng, Shandong, China, 252601
      • Liaocheng City Second People's Hospital
    • Liaocheng, Shandong, China
      • Dongchangfu people's Hospital
    • Liaocheng, Shandong, China
      • Liaocheng Central Hospital
    • Linqing, Shandong, China, 252600
      • Linqing People's Hospital
    • Qingdao, Shandong, China, 266000
      • Qingdao Municipal Hospital
    • Qingdao, Shandong, China, 266071
      • Affiliated Hospital of Qingdao University Medical College
    • Qingdao, Shandong, China, 266400
      • Qingdao West Coast New Area People's Hospital
    • Weifang, Shandong, China
      • Affiliated Hospital of Weifang Medical University
    • Weifang, Shandong, China
      • Sunshine Union Hospital
    • Weihai, Shandong, China, 264400
      • Weihai Central Hospital
    • Weihai, Shandong, China, 264400
      • Wendeng District People's Hospital
    • Yantai, Shandong, China, 265600
      • Penglai People's Hospital
    • Yantai, Shandong, China, 265701
      • Yantai Beihai Hospita
  • Shanghai
    • Shanghai, Shanghai, China, 200062
      • Putuo District Central Hospital
    • Shanghai, Shanghai, China, 200137
      • Shanghai 7th People's Hospital
  • Shanxi
    • Changzhi, Shanxi, China, 046000
      • Changzhi People's Hospital
    • Changzhi, Shanxi, China, 046000
      • Heping Hospital Affiliated to Changzhi Medical College
    • Datong, Shanxi, China, 037000
      • Datong Fifth People's Hospital
    • Datong, Shanxi, China, 037008
      • The Third People's Hospital of Datong
    • Taiyuan, Shanxi, China, 030024
      • Shanxi Cardiovascular Disease Hospital
    • Taiyuan, Shanxi, China, 30000
      • Shanxi Bethune Hospital
    • Taiyuan, Shanxi, China, 30001
      • Taiyuan Iron and Steel (Group) Co, Ltd,General Hospital
    • Taiyuan, Shanxi, China
      • The First Hospital of Shanxi Medical University
    • Xi'an, Shanxi, China
      • Xi 'an First Hospital
  • Shenzhen
    • Shenzhen, Shenzhen, China, 100191
      • Shenzhen Integrated Chinese and Western Medicine Hospital
    • Shenzhen, Shenzhen, China, 518001
      • Shenzhen Luohu People's Hospital
    • Shenzhen, Shenzhen, China, 518035
      • Shenzhen Second People's Hospital
    • Shenzhen, Shenzhen, China, 518052
      • Huazhong University of Science and Technology Union Shenzhen Hospital
  • Sichuan
    • Chengdou, Sichuan, China, 610041
      • West China Hospital of Sichuan University
    • Chengdu, Sichuan, China, 610000
      • Chengdu second Municipal People'sHospital
    • Chengdu, Sichuan, China, 610072
      • Sichuan Provincial People's Hospital
    • Dazhou, Sichuan, China, 635099
      • Dazhou Central Hospital
  • Tianjin
    • Tianjin, Tianjin, China, 300052
      • Tianjin Medical University General Hospital
  • Xinjiang Autonomous Region
    • Guiyang, Xinjiang Autonomous Region, China, 8300054
      • First Affiliated Hospital of Xinjiang Medical University
    • Urumqi, Xinjiang Autonomous Region, China, 830001
      • People's Hospital of Xinjiang Uygur Autonomous Region
    • Yining, Xinjiang Autonomous Region, China, 835000
      • Friendship Hospital of Ili Kazak Autonomous Prefecture
  • Yunnan
    • Kunming, Yunnan, China, 650000
      • First People's Hospital of Yunnan Province
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310006
      • Hangzhou First People's Hospital
    • Lishui, Zhejiang, China, 323000
      • Lishui Municipal Central Hospital
    • Ruian, Zhejiang, China, 325200
      • Zhejiang Wenzhou Medical College Third Affiliated Hospital
    • Taizhou, Zhejiang, China, 318020
      • Taizhou First People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ticagrelor plus Aspirin Group; Ticagrelor of loading dosing of 180mg followed by 90mg bid for 3 months plus aspirin of loading dose of 75-300mg followed by 75mg daily for 21 days	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
Active Comparator: Clopidogrel plus Aspirin Group; Clopidogrel of loading dosing of 300mg followed by 75mg daily for 3 months plus aspirin loading dose of 75-300mg followed by 75mg daily for 21 days	Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
All bleeding events	All bleeding events (severe/moderate bleeding and intracranial hemorrhage)	3 months and 1 year after randomization
Total mortality	Total mortality	3 months and 1 year after randomization
Incidence symptomatic intracranial hemorrhagic events	Incidence symptomatic intracranial hemorrhagic events	3 months and 1 year after randomization
Adverse events	Adverse events	3 months and 1 year after randomization

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital
• Collaborators: Ministry of Science and Technology of the People´s Republic of China
• Investigators: Principal Investigator: Yongjun Wang, M.D, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China

Publications and helpful links

General Publications

• Wang A, Xie X, Tian X, Johnston SC, Li H, Bath PM, Zuo Y, Jing J, Lin J, Wang Y, Zhao X, Li Z, Jiang Y, Liu L, Meng X, Wang Y. Ticagrelor-Aspirin Versus Clopidogrel-Aspirin Among CYP2C19 Loss-of-Function Carriers With Minor Stroke or Transient Ischemic Attack in Relation to Renal Function: A Post Hoc Analysis of the CHANCE-2 Trial. Ann Intern Med. 2022 Nov;175(11):1534-1542. doi: 10.7326/M22-1667. Epub 2022 Nov 1.
• Wang A, Meng X, Tian X, Johnston SC, Li H, Bath PM, Zuo Y, Xie X, Jing J, Lin J, Wang Y, Zhao X, Li Z, Jiang Y, Liu L, Wang F, Wang Y, Huang P, Chen G, Wang Y; CHANCE-2 Investigators. Effect of Hypertension on Efficacy and Safety of Ticagrelor-Aspirin Versus Clopidogrel-Aspirin in Minor Stroke or Transient Ischemic Attack. Stroke. 2022 Sep;53(9):2799-2808. doi: 10.1161/STROKEAHA.122.038662. Epub 2022 Jun 3.
• Wang Y, Meng X, Wang A, Xie X, Pan Y, Johnston SC, Li H, Bath PM, Dong Q, Xu A, Jing J, Lin J, Niu S, Wang Y, Zhao X, Li Z, Jiang Y, Li W, Liu L, Xu J, Chang L, Wang L, Zhuang X, Zhao J, Feng Y, Man H, Li G, Wang B; CHANCE-2 Investigators. Ticagrelor versus Clopidogrel in CYP2C19 Loss-of-Function Carriers with Stroke or TIA. N Engl J Med. 2021 Dec 30;385(27):2520-2530. doi: 10.1056/NEJMoa2111749. Epub 2021 Oct 28.
• Wang Y, Johnston C, Bath PM, Meng X, Jing J, Xie X, Wang A, Pan Y, Xu A, Dong Q, Wang Y, Zhao X, Li Z, Li H; CHANCE-2 Investigators. Clopidogrel with aspirin in High-risk patients with Acute Non-disabling Cerebrovascular Events II (CHANCE-2): rationale and design of a multicentre randomised trial. Stroke Vasc Neurol. 2021 Jun;6(2):280-285. doi: 10.1136/svn-2020-000791. Epub 2021 May 5.

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2019
• Primary Completion (Actual): June 24, 2021
• Study Completion (Actual): July 1, 2021

Study Registration Dates

• First Submitted: July 8, 2019
• First Submitted That Met QC Criteria: September 3, 2019
• First Posted (Actual): September 6, 2019

Study Record Updates

• Last Update Posted (Actual): December 2, 2021
• Last Update Submitted That Met QC Criteria: November 30, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: stroke; ticagrelor; clopidogrel; transient ischemic attack; acute treatment; acute non-disabling cerebrovascular event; clopidogrel combined with ASA; ticagrelor combined with ASA; recurrence of stroke and other vascular events; CYP2C19 loss-of-function allele(s) carrier
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Ischemic Attack, Transient; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Aspirin; Ticagrelor; Clopidogrel
• Other Study ID Numbers: 2017ZX09304018001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No