Platelet Aggregation Function-Guided De-Escalation Antiplatelet Therapy in Patients With Acute Ischemic Stroke
Summary
This multicenter, prospective, open-label, randomized controlled trial will evaluate whether platelet aggregation function-guided de-escalation of antiplatelet therapy is non-inferior in efficacy and superior in safety compared with standard dual antiplatelet therapy in patients with acute minor ischemic stroke or high-risk transient ischemic attack who are sensitive to clopidogrel. Participants who present within 48 hours of symptom onset and meet the eligibility criteria will receive loading doses of clopidogrel and aspirin, followed by platelet aggregation function testing. Eligible clopidogrel-sensitive participants will be randomized to receive either 7 days of dual antiplatelet therapy followed by clopidogrel monotherapy or standard 21-day dual antiplatelet therapy followed by single antiplatelet therapy. The primary efficacy outcome is new stroke within 90 days after randomization.
Timeline
- Start
- 2026-06
- Primary completion
- 2028-12
- Completion
- 2029-10
Publications
- Background Savcic M, Hauert J, Bachmann F, Wyld PJ, Geudelin B, Cariou R. Clopidogrel loading dose regimens: kinetic profile of pharmacodynamic response in healthy subjects. Semin Thromb Hemost. 1999;25 Suppl 2:15-9.
- Background Ma L, Chen W, Pan Y, Yan H, Li H, Meng X, Wang Y, Wang Y. Comparison of VerifyNow, thromboelastography, and PL-12 in patients with minor ischemic stroke or transient ischemic attack. Aging (Albany NY). 2021 Mar 3;13(6):8396-8407. doi: 10.18632/aging.202650. Epub 2021 Mar 3.
- Background Yang Y, Chen W, Pan Y, Yan H, Meng X, Liu L, Wang Y, Wang Y. Ticagrelor Is Superior to Clopidogrel in Inhibiting Platelet Reactivity in Patients With Minor Stroke or TIA. Front Neurol. 2020 Jun 10;11:534. doi: 10.3389/fneur.2020.00534. eCollection 2020.
- Background Tarantini G, Honton B, Paradies V, Lemesle G, Range G, Godin M, Mangin L, Cuisset T, Ruiz-Nodar JM, Brugaletta S, Lhermusier T, Piot C, De Poli F, Macia JC, Motreff P, Madera-Cambero M, Beygui F, Riccini P, Ranc S, Oreglia JA, Vaquerizo B, Poezevara Y, Bouchez D, Smits PC, Cayla G; TARGET-FIRST Investigators. Early Discontinuation of Aspirin after PCI in Low-Risk Acute Myocardial Infarction. N Engl J Med. 2025 Nov 27;393(21):2083-2094. doi: 10.1056/NEJMoa2508808. Epub 2025 Aug 31.
- Background Tarantini G, Smits PC, Lhermusier T, Honton B, Range G, Piot C, Lemesle G, Ruiz Nodar JM, Godin M, Madera Cambero M, Motreff P, Cuisset T, Bouchez D, Poezevara Y, Cayla G. A prospective study comparing short versus standard dual antiplatelet therapy in patients with acute myocardial infarction: design and rationale of the TARGET-FIRST trial. EuroIntervention. 2023 Jun 19;19(3):240-247. doi: 10.4244/EIJ-D-22-01006.
- Background Tavenier AH, Mehran R, Chiarito M, Cao D, Pivato CA, Nicolas J, Beerkens F, Nardin M, Sartori S, Baber U, Angiolillo DJ, Capodanno D, Valgimigli M, Hermanides RS, van 't Hof AWJ, Ten Berg JM, Chang K, Kini AS, Sharma SK, Dangas G. Guided and unguided de-escalation from potent P2Y12 inhibitors among patients with acute coronary syndrome: a meta-analysis. Eur Heart J Cardiovasc Pharmacother. 2022 Aug 11;8(5):492-502. doi: 10.1093/ehjcvp/pvab068.
- Background Kwon TJ, Tantry US, Park Y, Choi YM, Ahn JH, Kim KH, Koh JS, Park JR, Hwang SJ, Kwak CH, Hwang JY, Gurbel PA, Smith SC Jr, Jeong YH. Influence of platelet reactivity on BARC classification in East Asian patients undergoing percutaneous coronary intervention. Results of the ACCEL-BLEED study. Thromb Haemost. 2016 May 2;115(5):979-92. doi: 10.1160/TH15-05-0366. Epub 2016 Jan 21.
- Background Valgimigli M, Choi KH, Giacoppo D, Gragnano F, Kimura T, Watanabe H, Kim HS, Kang J, Park KW, Pettersen AA, Woodward M, Bhatt DL, Calabro P, Angiolillo DJ, Mehran R, Song YB, Hahn JY. Clopidogrel versus aspirin for secondary prevention of coronary artery disease: a systematic review and individual patient data meta-analysis. Lancet. 2025 Sep 13;406(10508):1091-1102. doi: 10.1016/S0140-6736(25)01562-4. Epub 2025 Aug 31.
- Background Kaushik A, Deora S, Choudhary R. Ticagrelor and Aspirin or Aspirin Alone in Acute Ischemic Stroke or TIA. N Engl J Med. 2020 Oct 22;383(17):1692-1693. doi: 10.1056/NEJMc2027491. No abstract available.
- Background Gao Y, Chen W, Pan Y, Jing J, Wang C, Johnston SC, Amarenco P, Bath PM, Jiang L, Yang Y, Wang T, Han S, Meng X, Lin J, Zhao X, Liu L, Zhao J, Li Y, Zang Y, Zhang S, Yang H, Yang J, Wang Y, Li D, Wang Y, Liu D, Kang G, Wang Y, Wang Y; INSPIRES Investigators. Dual Antiplatelet Treatment up to 72 Hours after Ischemic Stroke. N Engl J Med. 2023 Dec 28;389(26):2413-2424. doi: 10.1056/NEJMoa2309137.
- Background Wang Y, Wang Y, Zhao X, Liu L, Wang D, Wang C, Wang C, Li H, Meng X, Cui L, Jia J, Dong Q, Xu A, Zeng J, Li Y, Wang Z, Xia H, Johnston SC; CHANCE Investigators. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med. 2013 Jul 4;369(1):11-9. doi: 10.1056/NEJMoa1215340. Epub 2013 Jun 26.
- Background Depta JP, Fowler J, Novak E, Katzan I, Bakdash S, Kottke-Marchant K, Bhatt DL. Clinical outcomes using a platelet function-guided approach for secondary prevention in patients with ischemic stroke or transient ischemic attack. Stroke. 2012 Sep;43(9):2376-81. doi: 10.1161/STROKEAHA.112.655084. Epub 2012 Jun 19.
- Background Yi X, Lin J, Wang C, Huang R, Han Z, Li J. Platelet function-guided modification in antiplatelet therapy after acute ischemic stroke is associated with clinical outcomes in patients with aspirin nonresponse. Oncotarget. 2017 Nov 7;8(63):106258-106269. doi: 10.18632/oncotarget.22293. eCollection 2017 Dec 5.
- Background Kim HS, Kang J, Hwang D, Han JK, Yang HM, Kang HJ, Koo BK, Rhew JY, Chun KJ, Lim YH, Bong JM, Bae JW, Lee BK, Park KW; HOST-REDUCE-POLYTECH-ACS investigators. Prasugrel-based de-escalation of dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndrome (HOST-REDUCE-POLYTECH-ACS): an open-label, multicentre, non-inferiority randomised trial. Lancet. 2020 Oct 10;396(10257):1079-1089. doi: 10.1016/S0140-6736(20)31791-8. Epub 2020 Aug 31.
- Background Venketasubramanian N, Agustin SJ, Padilla JL, Yumul MP, Sum C, Lee SH, Ponnudurai K, Gan RN. Comparison of Different Laboratory Tests to Identify "Aspirin Resistance" and Risk of Vascular Events among Ischaemic Stroke Patients: A Double-Blind Study. J Cardiovasc Dev Dis. 2022 May 12;9(5):156. doi: 10.3390/jcdd9050156.
- Background Aradi D, Gross L, Trenk D, Geisler T, Merkely B, Kiss RG, Komocsi A, Dezsi CA, Ruzsa Z, Ungi I, Rizas KD, May AE, Mugge A, Zeiher AM, Holdt L, Huber K, Neumann FJ, Koltowski L, Huczek Z, Hadamitzky M, Massberg S, Sibbing D. Platelet reactivity and clinical outcomes in acute coronary syndrome patients treated with prasugrel and clopidogrel: a pre-specified exploratory analysis from the TROPICAL-ACS trial. Eur Heart J. 2019 Jun 21;40(24):1942-1951. doi: 10.1093/eurheartj/ehz202.
- Background Yue C, Lin Z, Lu C, Chen H. Efficacy of Monitoring Platelet Function by an Automated PL-12 Analyzer During the Treatment of Acute Cerebral Infarction With Antiplatelet Medicine. Clin Appl Thromb Hemost. 2021 Jan-Dec;27:10760296211001119. doi: 10.1177/10760296211001119.
- Background Zheng YY, Wu TT, Yang Y, Hou XG, Gao Y, Chen Y, Yang YN, Li XM, Ma X, Ma YT, Xie X. Personalized antiplatelet therapy guided by a novel detection of platelet aggregation function in stable coronary artery disease patients undergoing percutaneous coronary intervention: a randomized controlled clinical trial. Eur Heart J Cardiovasc Pharmacother. 2020 Jul 1;6(4):211-221. doi: 10.1093/ehjcvp/pvz059.
- Background Schaefer JH, Lieschke F, Urban H, Bohmann FO, Gatzke F, Miesbach W. Feasibility and comparability of different platelet function tests in acute stroke with or without prior antiplatelet therapy. Front Neurol. 2024 Feb 12;15:1361751. doi: 10.3389/fneur.2024.1361751. eCollection 2024.
- Background Berg DD, Yeh RW, Mauri L, Morrow DA, Kereiakes DJ, Cutlip DE, Gao Q, Jarolim P, Michelson AD, Frelinger AL 3rd, Cange AL, Sabatine MS, O'Donoghue ML. Biomarkers of platelet activation and cardiovascular risk in the DAPT trial. J Thromb Thrombolysis. 2021 Apr;51(3):675-681. doi: 10.1007/s11239-020-02221-5.
- Background Capodanno D, Angiolillo DJ. Personalised antiplatelet therapies for coronary artery disease: what the future holds. Eur Heart J. 2023 Aug 22;44(32):3059-3072. doi: 10.1093/eurheartj/ehad362.
- Background Wisniewski A, Filipska K. The Phenomenon of Clopidogrel High On-Treatment Platelet Reactivity in Ischemic Stroke Subjects: A Comprehensive Review. Int J Mol Sci. 2020 Sep 3;21(17):6408. doi: 10.3390/ijms21176408.
- Background Wang Y, Maeda T, You S, Chen C, Liu L, Zhou Z, Robinson TG, Lindley RI, Delcourt C, Mair G, Wardlaw JM, Chalmers JP, Arima H, Huang Y, Kim JS, Lavados PM, Lee TH, Levi C, Parsons MW, Martins SC, Pandian JD, Pontes-Neto OM, Sharma VK, Nguyen TH, Wang J, Wu S, Liu M, Anderson CS, Chen X; ENCHANTED Investigators. Patterns and Clinical Implications of Hemorrhagic Transformation After Thrombolysis in Acute Ischemic Stroke: Results From the ENCHANTED Study. Neurology. 2024 Dec 10;103(11):e210020. doi: 10.1212/WNL.0000000000210020. Epub 2024 Nov 14.
- Background Pan Y, Jing J, Chen W, Meng X, Li H, Zhao X, Liu L, Wang D, Johnston SC, Wang Y, Wang Y; CHANCE investigators. Risks and benefits of clopidogrel-aspirin in minor stroke or TIA: Time course analysis of CHANCE. Neurology. 2017 May 16;88(20):1906-1911. doi: 10.1212/WNL.0000000000003941. Epub 2017 Apr 19.
- Background Johnston SC, Easton JD, Farrant M, Barsan W, Conwit RA, Elm JJ, Kim AS, Lindblad AS, Palesch YY; Clinical Research Collaboration, Neurological Emergencies Treatment Trials Network, and the POINT Investigators. Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA. N Engl J Med. 2018 Jul 19;379(3):215-225. doi: 10.1056/NEJMoa1800410. Epub 2018 May 16.
- Background Sibbing D, Aradi D, Jacobshagen C, Gross L, Trenk D, Geisler T, Orban M, Hadamitzky M, Merkely B, Kiss RG, Komocsi A, Dezsi CA, Holdt L, Felix SB, Parma R, Klopotowski M, Schwinger RHG, Rieber J, Huber K, Neumann FJ, Koltowski L, Mehilli J, Huczek Z, Massberg S; TROPICAL-ACS Investigators. Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention (TROPICAL-ACS): a randomised, open-label, multicentre trial. Lancet. 2017 Oct 14;390(10104):1747-1757. doi: 10.1016/S0140-6736(17)32155-4. Epub 2017 Aug 28.
- Background Galli M, Benenati S, Capodanno D, Franchi F, Rollini F, D'Amario D, Porto I, Angiolillo DJ. Guided versus standard antiplatelet therapy in patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis. Lancet. 2021 Apr 17;397(10283):1470-1483. doi: 10.1016/S0140-6736(21)00533-X.
- Background He D, Guo Y, Zhang Y, Zhao J, Wu L, Yu Z, Qu W, Luo X. Thromboelastography predicts dual antiplatelet therapy-related hemorrhage in patients with acute ischemic stroke. J Neurointerv Surg. 2022 Jul;14(7):672-676. doi: 10.1136/neurintsurg-2021-017615. Epub 2021 Jul 29.
- Background Angiolillo DJ, Galli M, Alexopoulos D, Aradi D, Bhatt DL, Bonello L, Capodanno D, Cavallari LH, Collet JP, Cuisset T, Ferreiro JL, Franchi F, Geisler T, Gibson CM, Gorog DA, Gurbel PA, Jeong YH, Marcucci R, Siller-Matula JM, Mehran R, Neumann FJ, Pereira NL, Rizas KD, Rollini F, So DYF, Stone GW, Storey RF, Tantry US, Berg JT, Trenk D, Valgimigli M, Waksman R, Sibbing D. International Consensus Statement on Platelet Function and Genetic Testing in Percutaneous Coronary Intervention: 2024 Update. JACC Cardiovasc Interv. 2024 Nov 25;17(22):2639-2663. doi: 10.1016/j.jcin.2024.08.027.
- Background Risks and benefits of clopidogrel-aspirin in minor stroke or TIA: Time course analysis of CHANCE. Neurology. 2019 Aug 13;93(7):322. doi: 10.1212/WNL.0000000000007482. No abstract available.
- Background Trifan G, Gorelick PB, Testai FD. Efficacy and Safety of Using Dual Versus Monotherapy Antiplatelet Agents in Secondary Stroke Prevention: Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials. Circulation. 2021 Jun 22;143(25):2441-2453. doi: 10.1161/CIRCULATIONAHA.121.053782. Epub 2021 Apr 30.
- Background Lee M, Saver JL, Hong KS, Rao NM, Wu YL, Ovbiagele B. Risk-benefit profile of long-term dual- versus single-antiplatelet therapy among patients with ischemic stroke: a systematic review and meta-analysis. Ann Intern Med. 2013 Oct 1;159(7):463-70. doi: 10.7326/0003-4819-159-7-201310010-00006.
- Background Dawson J, Bejot Y, Christensen LM, De Marchis GM, Dichgans M, Hagberg G, Heldner MR, Milionis H, Li L, Pezzella FR, Taylor Rowan M, Tiu C, Webb A. European Stroke Organisation (ESO) guideline on pharmacological interventions for long-term secondary prevention after ischaemic stroke or transient ischaemic attack. Eur Stroke J. 2022 Sep;7(3):I-II. doi: 10.1177/23969873221100032. Epub 2022 Jun 3.
- Background Tu WJ, Zhao Z, Yin P, Cao L, Zeng J, Chen H, Fan D, Fang Q, Gao P, Gu Y, Tan G, Han J, He L, Hu B, Hua Y, Kang D, Li H, Liu J, Liu Y, Lou M, Luo B, Pan S, Peng B, Ren L, Wang L, Wu J, Xu Y, Xu Y, Yang Y, Zhang M, Zhang S, Zhu L, Zhu Y, Li Z, Chu L, An X, Wang L, Yin M, Li M, Yin L, Yan W, Li C, Tang J, Zhou M, Wang L. Estimated Burden of Stroke in China in 2020. JAMA Netw Open. 2023 Mar 1;6(3):e231455. doi: 10.1001/jamanetworkopen.2023.1455.
- Background Tu WJ, Wang LD; Special Writing Group of China Stroke Surveillance Report. China stroke surveillance report 2021. Mil Med Res. 2023 Jul 19;10(1):33. doi: 10.1186/s40779-023-00463-x.
- Background Li XY, Kong XM, Yang CH, Cheng ZF, Lv JJ, Guo H, Liu XH. Global, regional, and national burden of ischemic stroke, 1990-2021: an analysis of data from the global burden of disease study 2021. EClinicalMedicine. 2024 Jul 27;75:102758. doi: 10.1016/j.eclinm.2024.102758. eCollection 2024 Sep.
- Background He Q, Wang W, Zhang Y, Xiong Y, Tao C, Ma L, Ma J, You C, Wang C. Global, Regional, and National Burden of Stroke, 1990-2021: A Systematic Analysis for Global Burden of Disease 2021. Stroke. 2024 Dec;55(12):2815-2824. doi: 10.1161/STROKEAHA.124.048033. Epub 2024 Oct 17.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Aspirin | Small molecule | 100 mg | Oral |
| Subject | Clopidogrel | Small molecule | 75 mg | Oral |