Precision Antiplatelet Therapy Guided by Platelet Aggregation Function in Patients With Acute Ischemic STROKE

NCT06853535 | Recruiting Phase 3 DMC

• 1 other identifier: IITLX2025007
• Study Type: interventional
• Target: 5,138
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this clinical trial is to evaluate the efficacy and safety of platelet aggregation function - guided precision anti - platelet therapy in patients with acute cerebral infarction. The main question it aims to answer is: among the cerebral infarction patients with possible clopidogrel resistance detected by platelet aggregation function tests, what is the efficacy and safety of using ticagrelor to replace the clopidogrel treatment regimen.

Conditions

Acute Ischemic Stroke; Clopidogrel Resistance

Outcome Measures

Primary Outcomes (1)

• Recurrent stroke (including ischemic and hemorrhagic stroke) within 90 days

  within 90 days

Secondary Outcomes (6)

• Recurrent ischemic stroke

  On the 7th day, at 30 days, and within 1 year

• New-onset vascular events

  On the 7th day, at 30 days, at 90 days and within 1 year.

• Modified Rankin Scale (mRS) score

  at 30 days, 90 days, and 1 year

• Recurrent stroke

  On the 7th day, the 30th day, the 90th day and within one year.

• Worsening of nerve damage (an increase in the NIHSS score by ≥ 4 points compared to the baseline)

  At the 24th hour and on the 7th day

Study Arms (2)

The ticagrelor

EXPERIMENTAL

Ticagrelor 90 mg should be administered as early as possible (within 12-24 hours after the loading dose). From Day 1 to Day 21 after enrollment: Patients shall receive dual antiplatelet therapy with oral ticagrelor 90 mg bid and aspirin 100 mg qd. From Day 22 to Day 90 after enrollment: Patients shall receive monotherapy with oral ticagrelor 90 mg bid.

Drug: The ticagrelor

The Clopidogrel

OTHER

From the 1st to the 21st day, the patient should receive dual anti - platelet therapy with clopidogrel 75mg once a day (qd) combined with aspirin 100mg once a day (qd). From the 22nd to the 90th day, the patient should be given clopidogrel 75mg qd for anti - platelet treatment.

Drug: The Clopidogrel

Interventions

The ticagrelor DRUG

Ticagrelor 90 mg should be administered as early as possible (within 12-24 hours after the loading dose). From Day 1 to Day 21 after enrollment: Patients shall receive dual antiplatelet therapy with oral ticagrelor 90 mg bid and aspirin 100 mg qd. From Day 22 to Day 90 after enrollment: Patients shall receive monotherapy with oral ticagrelor 90 mg bid.

The ticagrelor

The Clopidogrel DRUG

From the 1st to the 21st day, the patient should receive dual anti - platelet therapy with clopidogrel 75mg once a day (qd) combined with aspirin 100mg once a day (qd). From the 22nd to the 90th day, the patient should be given clopidogrel 75mg qd for anti - platelet treatment.

The Clopidogrel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years old.
• Patients diagnosed with acute non-disabling ischaemic stroke or transient ischaemic attack (TIA) with moderate to high stroke risk in accordance with the WHO diagnostic criteria, defined as follows:
• Acute non-disabling ischaemic stroke: NIHSS score ≤ 5 at enrollment;
• TIA with moderate to high stroke risk: ABCD₂ score ≥ 4.
• Time from symptom onset ≤ 48 hours. (Definition of symptom onset time: the interval from the last time the patient was observed in a normal state to the time of co-administration of clopidogrel 300 mg and aspirin 100 mg.)
• MARADP ≥ 35% measured at 5-20 hours after the patient received antiplatelet therapy with co-administration of clopidogrel 300 mg and aspirin 100 mg within 48 hours of symptom onset.
• Written informed consent signed by the patient or their legal representative.

You may not qualify if:

• Imaging examinations suggestive of hemorrhagic stroke, hemorrhagic transformation, or other pathological cerebral disorders, such as vascular malformation, tumor, abscess, or other common non-ischemic cerebral diseases (e.g., multiple sclerosis).
• Minor stroke/TIA induced by angioplasty or vascular surgery.
• Routine electrocardiogram (ECG) suggestive of atrial fibrillation (AF), or physical examination findings of typical AF signs including completely irregular cardiac rhythm, variable intensity of the first heart sound, and pulse deficit.
• Having definite indications for anticoagulant therapy (suspected cardiogenic embolism, e.g., atrial fibrillation, known artificial heart valve, suspected endocarditis, etc.).
• Patients who have received intravenous thrombolysis, intra-arterial thrombolysis, mechanical thrombectomy, or any revascularization surgery after the current onset, or plan to receive such procedures within 90 days.
• Use of antiplatelet agents other than aspirin and clopidogrel (e.g., ticagrelor, prasugrel) within 7 days.
• History of gastrointestinal bleeding, intracranial hemorrhage, massive hemorrhage or blood transfusion in the recent period (excluding mild hemoptysis and mild abnormal vaginal bleeding), or history of other hemorrhagic diseases caused by coagulation dysfunction (e.g., purpura).
• Having contraindications to or intolerance of clopidogrel, ticagrelor, or aspirin, including:
• Known history of hypersensitivity;
• Severe hepatic or renal insufficiency (definition of severe hepatic insufficiency: ALT \> 2× upper limit of normal \[ULN\] or AST \> 2× ULN; definition of severe renal insufficiency: creatinine \> 1.5× ULN);
• Severe heart failure (NYHA Class Ⅲ or Ⅳ);
• Coagulation disorders or history of systemic hemorrhage;
• History of previous thrombocytopenia or neutropenia;
• History of previous drug-induced hematological diseases or hepatic dysfunction.
• Leukopenia (\< 2×10⁹/L) or thrombocytopenia (\< 100×10⁹/L).

Sponsors & Collaborators

• Sichuan Provincial People's Hospital: lead
• Fudan University: collaborator
• Chengdu Medical College: collaborator

Study Sites (1)

Sichuan Provincial People's Hospital

Chengdu, Sichuan, 610072, China

RECRUITING

Related Publications (21)

• 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.

  PMID: 32587571 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.

  PMID: 10440417 BACKGROUND

• Wang Y, Chen W, Lin Y, Meng X, Chen G, Wang Z, Wu J, Wang D, Li J, Cao Y, Xu Y, Zhang G, Li X, Pan Y, Li H, Zhao X, Liu L, Lin J, Dong K, Jing J, Johnston SC, Wang D, Wang Y; PRINCE Protocol Steering Group. Ticagrelor plus aspirin versus clopidogrel plus aspirin for platelet reactivity in patients with minor stroke or transient ischaemic attack: open label, blinded endpoint, randomised controlled phase II trial. BMJ. 2019 Jun 6;365:l2211. doi: 10.1136/bmj.l2211.

  PMID: 31171523 BACKGROUND

• Zhu HC, Li Y, Guan SY, Li J, Wang XZ, Jing QM, Wang ZL, Han YL. Efficacy and safety of individually tailored antiplatelet therapy in patients with acute coronary syndrome after coronary stenting: a single center, randomized, feasibility study. J Geriatr Cardiol. 2015 Jan;12(1):23-9. doi: 10.11909/j.issn.1671-5411.2015.01.003.

  PMID: 25678901 BACKGROUND

• Cayla G, Cuisset T, Silvain J, Leclercq F, Manzo-Silberman S, Saint-Etienne C, Delarche N, Bellemain-Appaix A, Range G, El Mahmoud R, Carrie D, Belle L, Souteyrand G, Aubry P, Sabouret P, du Fretay XH, Beygui F, Bonnet JL, Lattuca B, Pouillot C, Varenne O, Boueri Z, Van Belle E, Henry P, Motreff P, Elhadad S, Salem JE, Abtan J, Rousseau H, Collet JP, Vicaut E, Montalescot G; ANTARCTIC investigators. Platelet function monitoring to adjust antiplatelet therapy in elderly patients stented for an acute coronary syndrome (ANTARCTIC): an open-label, blinded-endpoint, randomised controlled superiority trial. Lancet. 2016 Oct 22;388(10055):2015-2022. doi: 10.1016/S0140-6736(16)31323-X. Epub 2016 Aug 28.

  PMID: 27581531 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.

  PMID: 33865495 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.

  PMID: 31603191 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.

  PMID: 33686963 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.

  PMID: 33749312 BACKGROUND

• 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.

  PMID: 34708996 BACKGROUND

• Yi X, Lin J, Zhou Q, Wu L, Cheng W, Wang C. Clopidogrel Resistance Increases Rate of Recurrent Stroke and Other Vascular Events in Chinese Population. J Stroke Cerebrovasc Dis. 2016 May;25(5):1222-1228. doi: 10.1016/j.jstrokecerebrovasdis.2016.02.013. Epub 2016 Feb 28.

  PMID: 26935114 BACKGROUND

• Wu Y, Shen H, Cai B, Chen C, Yin Q, Zhao Y, Zhou G. Factors associated with clopidogrel resistance and clinical outcomes in ischemic cerebrovascular disease: A retrospective study. J Stroke Cerebrovasc Dis. 2024 Jun;33(6):107684. doi: 10.1016/j.jstrokecerebrovasdis.2024.107684. Epub 2024 Mar 20.

  PMID: 38518890 BACKGROUND

• Estevez B, Du X. New Concepts and Mechanisms of Platelet Activation Signaling. Physiology (Bethesda). 2017 Mar;32(2):162-177. doi: 10.1152/physiol.00020.2016.

  PMID: 28228483 BACKGROUND

• Franchi F, Rollini F, Angiolillo DJ. Antithrombotic therapy for patients with STEMI undergoing primary PCI. Nat Rev Cardiol. 2017 Jun;14(6):361-379. doi: 10.1038/nrcardio.2017.18. Epub 2017 Feb 23.

  PMID: 28230176 BACKGROUND

• Mastenbroek TG, van Geffen JP, Heemskerk JW, Cosemans JM. Acute and persistent platelet and coagulant activities in atherothrombosis. J Thromb Haemost. 2015 Jun;13 Suppl 1:S272-80. doi: 10.1111/jth.12972.

  PMID: 26149036 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.

  PMID: 38157499 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.

  PMID: 23803136 BACKGROUND

• Liu L, Wang D, Wong KS, Wang Y. Stroke and stroke care in China: huge burden, significant workload, and a national priority. Stroke. 2011 Dec;42(12):3651-4. doi: 10.1161/STROKEAHA.111.635755. Epub 2011 Nov 3.

  PMID: 22052510 BACKGROUND

• Wang W, Jiang B, Sun H, Ru X, Sun D, Wang L, Wang L, Jiang Y, Li Y, Wang Y, Chen Z, Wu S, Zhang Y, Wang D, Wang Y, Feigin VL; NESS-China Investigators. Prevalence, Incidence, and Mortality of Stroke in China: Results from a Nationwide Population-Based Survey of 480 687 Adults. Circulation. 2017 Feb 21;135(8):759-771. doi: 10.1161/CIRCULATIONAHA.116.025250. Epub 2017 Jan 4.

  PMID: 28052979 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.

  PMID: 36862407 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.

  PMID: 37468952 BACKGROUND

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Central Study Contacts

Jie Yang Deputy Director of the Department of Neurology

CONTACT

+8613678130516; yangjie1126@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deputy Director of the Department of Neurology

Study Record Dates

• First Submitted: February 18, 2025
• First Posted: March 3, 2025
• Study Start: May 23, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: January 21, 2026

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)