drugset / Trial / NCT04078737
Clopidogrel With Aspirin in High-risk Patients With Acute Non-disabling Cerebrovascular Events II
Phase 3
Completed
6412 enrolled
Beijing Tiantan Hospital
Ministry of Science and Technology of the People´s Republic of China · collab
RandomizedParallel-groupQuadruple-blindPrevention
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.
Timeline
- Start
- 2019-09-23
- Primary completion
- 2021-06-24
- Completion
- 2021-07-01
Outcome
Met primary endpoint
paper Stroke occurred within 90 days in 191 patients (6.0%) in the ticagrelor group and 243 patients (7.6%) in the clopidogrel group (hazard ratio, 0.77; 95% confidence interval, 0.64 to 0.94; P = 0.008). PMID 34708996 ↗
paper Among Chinese patients with minor ischemic stroke or TIA who were carriers of CYP2C19 loss-of-function alleles, the risk of stroke at 90 days was modestly lower with ticagrelor than with clopidogrel. PMID 34708996 ↗
Publications
- Zhao J, Tian X, Yang X, Xu Q, Xia X, Zhang Y, Xie X, Bath PM, Jing J, Wang Y, Meng X, Wang A. Effect of insulin resistance on ticagrelor-versus clopidogrel-based dual antiplatelet therapy for secondary prevention of stroke in carriers of CYP2C19 loss-of-function mutations. CMAJ. 2026 Jan 18;198(2):E36-E43. doi: 10.1503/cmaj.241581.
- Lin J, Zhou H, Wang Y, Jin A, Li S, Zhang L, Meng X, Xie X, Jing J, Jiang Y, Wang Y, Zhao X, Li H, Li Z, Wang Y; CHANCE-2 Investigators. Lp-PLA2 Activity and Genotype-Guided Dual Antiplatelet Therapy in Minor Stroke or Transient Ischemic Attack. Stroke. 2026 Apr;57(4):890-896. doi: 10.1161/STROKEAHA.125.052954. Epub 2026 Jan 13.
- Li H, Xia X, Xu Q, Meng X, Wang Y, Wang A. Differential Effect of Ticagrelor Versus Clopidogrel by Causative Classification of Stroke Classification and Vascular Cellular Adhesion Molecule-1 Level on the Risk of Recurrent Stroke: A Post Hoc Analysis of the CHANCE-2 Trial. J Am Heart Assoc. 2026 Jan 6;15(1):e042259. doi: 10.1161/JAHA.125.042259. Epub 2025 Dec 18.
- Feng Z, Zhang F, Jin A, Li X, Li Y, Chu Q, Xue J, Cheng A, Lin J, Li H, Meng X, Wang Y, Xu J. Genotype-guided dual antiplatelet therapy in minor stroke or transient ischemic attack with metabolic syndrome: A post hoc analysis of CHANCE-2. Diabetes Obes Metab. 2026 Jan;28(1):625-633. doi: 10.1111/dom.70243. Epub 2025 Oct 27.
- Lin X, Guo C, Meng X, Zhao X, Li H, Wang Y, Yang J. PCISOS Risk Profiles Stratify Heterogeneous Outcomes in Minor Posterior Circulation Ischemic Stroke: A Post Hoc Analysis of the CHANCE-2 Trial. Stroke. 2025 Dec;56(12):3371-3381. doi: 10.1161/STROKEAHA.125.053054. Epub 2025 Sep 10.
- Xie X, Jing J, Wang A, Xu Q, Zhao X, Lin J, Chen P, Jiang Y, Wang Y, Li H, Meng X, Wang Y. Dual antiplatelet therapy with ticagrelor vs clopidogrel in patients with TIA or minor stroke with or without symptomatic carotid artery stenosis: a post hoc analysis of the CHANCE-2 trial. Stroke Vasc Neurol. 2025 Oct 27;10(5):551-559. doi: 10.1136/svn-2024-003293.
- Xie X, Jing J, Meng X, Johnston SC, Bath PM, Li Z, Zhao X, Wang Y, Xu Q, Wang A, Jiang Y, Li H, Wang Y; CHANCE-2 Investigators. Dual Antiplatelet Therapy After Embolic Stroke of Undetermined Source: A Subgroup Analysis of the CHANCE-2 Trial. Stroke. 2024 Jul;55(7):1739-1747. doi: 10.1161/STROKEAHA.124.046834. Epub 2024 Jun 11.
- Wang A, Tian X, Xie X, Li H, Bath PM, Jing J, Lin J, Wang Y, Zhao X, Li Z, Liu L, Wang Y, Meng X. Differential effect of ticagrelor versus clopidogrel by homocysteine levels on risk of recurrent stroke: a post hoc analysis of the CHANCE-2 trial. CMAJ. 2024 Feb 11;196(5):E149-E156. doi: 10.1503/cmaj.231262.
- Zhang X, Jing J, Wang A, Xie X, Johnston SC, Li H, Bath PM, Xu Q, Lin J, Wang Y, Zhao X, Li Z, Jiang Y, Liu L, Chen W, Gong X, Li J, Han X, Meng X, Wang Y. Efficacy and safety of dual antiplatelet therapy in the elderly for stroke prevention: a subgroup analysis of the CHANCE-2 trial. Stroke Vasc Neurol. 2024 Nov 5;9(5):541-550. doi: 10.1136/svn-2023-002450.
- Meng X, Wang A, Tian X, Johnston C, Li H, Bath PM, Xu Q, Zhang Y, Xie X, Jing J, Lin J, Wang Y, Zhao X, Li Z, Jiang Y, Liu L, Wang Y. One-Year Outcomes of Early Therapy With Ticagrelor vs Clopidogrel in CYP2C19 Loss-of-Function Carriers With Stroke or TIA Trial. Neurology. 2024 Feb 13;102(3):e207809. doi: 10.1212/WNL.0000000000207809. Epub 2024 Jan 5.
- Wang A, Tian X, Xie X, Li H, Jing J, Lin J, Wang Y, Zhao X, Li Z, Liu L, Wang Y, Meng X. Effects of remnant cholesterol on the efficacy of genotype-guided dual antiplatelet in CYP2C19 loss-of -function carriers with minor stroke or transient ischaemic attack: a post-hoc analysis of the CHANCE-2 trial. EClinicalMedicine. 2023 Dec 2;67:102357. doi: 10.1016/j.eclinm.2023.102357. eCollection 2024 Jan.
- Wang C, Jia W, Jing J, Meng X, Wang A, Xu Q, Zhang X, Pan Y, Xie X, Johnston SC, Bath PM, Lin J, Jiang Y, Li H, Wang Y, Zhao X, Liu L, Li Z, Wang Y; CHANCE-2 Investigators. Ticagrelor Versus Clopidogrel in Minor Stroke or Transient Ischemic Attack With Intracranial Artery Stenosis: A Post Hoc Analysis of CHANCE-2. J Am Heart Assoc. 2023 Nov 7;12(21):e031611. doi: 10.1161/JAHA.123.031611. Epub 2023 Oct 27.
- Xie X, Jing J, Meng X, Claiborne Johnston S, Bath PM, Li Z, Zhao X, Liu L, Wang Y, Xu Q, Wang A, Jiang Y, Li H, Wang Y; CHANCE-2 Investigators. Dual Antiplatelet Therapies and Causes in Minor Stroke or Transient Ischemic Attack: A Prespecified Analysis in the CHANCE-2 Trial. Stroke. 2023 Sep;54(9):2241-2250. doi: 10.1161/STROKEAHA.122.042233. Epub 2023 Aug 7.
- Zhang J, Wang A, Tian X, Meng X, Xie X, Jing J, Lin J, Wang Y, Li Z, Liu L, Li H, Jiang Y, Zhao X, Wang Y. Impact of body mass index on efficacy and safety of ticagrelor versus clopidogrel in patients with minor stroke or transient ischemic attack. CMAJ. 2023 Jul 10;195(26):E897-E904. doi: 10.1503/cmaj.230262.
- Xie X, Johnston SC, Wang A, Xu Q, Bath PM, Pan Y, Li H, Lin J, Wang Y, Zhao X, Li Z, Jiang Y, Liu L, Xu A, Jing J, Meng X, Wang Y. Association of CYP2C19 Loss-of-Function Metabolizer Status With Stroke Risk Among Chinese Patients Treated With Ticagrelor-Aspirin vs Clopidogrel-Aspirin: A Prespecified Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2023 Jun 1;6(6):e2317037. doi: 10.1001/jamanetworkopen.2023.17037.
- Liu H, Jing J, Wang A, Xu Q, Meng X, Li H, Li Z, Wang Y. Stroke Recurrence and Antiplatelets in Posterior Versus Anterior Circulation Minor Stroke or Transient Ischemic Attack. Stroke. 2023 Apr;54(4):964-972. doi: 10.1161/STROKEAHA.122.041738. Epub 2023 Feb 15.
- Jing J, Xie X, Johnston SC, Bath PM, Li Z, Zhao X, Liu L, Wang Y, Xu Q, Wang A, Jiang Y, Li H, Meng X, Wang Y; CHANCE-2 Investigators. Genotype-Guided Dual Antiplatelet Use for Transient Ischemic Attack and Minor Stroke by Imaging Status: Subgroup Analysis of the CHANCE-2 Trial. Ann Neurol. 2023 Apr;93(4):783-792. doi: 10.1002/ana.26589. Epub 2023 Jan 20.
- Wang A, Meng X, Tian X, Zuo Y, Bath PM, Li H, Xie X, Jing J, Lin J, Wang Y, Zhao X, Liu L, Li Z, Jiang Y, Xu J, Wang F, Chen W, Cao M, Li J, Wang Y. Ticagrelor Aspirin vs Clopidogrel Aspirin in CYP2C19 Loss-of-Function Carriers With Minor Stroke or TIA Stratified by Risk Profile. Neurology. 2023 Jan 31;100(5):e497-e504. doi: 10.1212/WNL.0000000000201454. Epub 2022 Dec 19.
- 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.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Comparator | Clopidogrel | Small molecule | 75 mg | — |
| Subject | Ticagrelor | Small molecule | 90 mg | — |
| Background | Aspirin | Small molecule | 75 mg | — |