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| Name | Class |
|---|---|
| Fudan University | OTHER |
| Chengdu Medical College | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Recurrent stroke (including ischemic and hemorrhagic stroke) within 90 days | within 90 days |
| Measure | Description | Time Frame |
|---|---|---|
| Recurrent ischemic stroke | On the 7th day, at 30 days, and within 1 year | |
| New-onset vascular events | Including cardiovascular and cerebrovascular strokes, myocardial infarctions, and vascular deaths. |
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Inclusion Criteria:
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:
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.
Exclusion Criteria:
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:
Leukopenia (< 2×10⁹/L) or thrombocytopenia (< 100×10⁹/L).
Use of heparin or oral anticoagulants within 10 days prior to enrollment.
Patients with severe cardiac, pulmonary, hepatic, or renal insufficiency, and those with severe comorbidities (e.g., malignancy, chronic airflow limitation, severe dementia, severe heart failure).
Women of childbearing age with a negative pregnancy test but who refuse to adopt effective contraceptive measures; pregnant or lactating women.
Poor compliance, unable to cooperate with the requirements of the study.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jie Yang Deputy Director of the Department of Neurology | Contact | +8613678130516 | yangjie1126@163.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sichuan Provincial People's Hospital | Recruiting | Chengdu | Sichuan | 610072 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32587571 | 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. | |
| 10440417 | 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. |
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| ID | Term |
|---|---|
| D000083242 | Ischemic Stroke |
| ID | Term |
|---|---|
| D020521 | Stroke |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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|
| 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. |
|
| On the 7th day, at 30 days, at 90 days and within 1 year. |
| Modified Rankin Scale (mRS) score | The score range of the scale is from 0 to 6. The higher the score, the worse the outcome. | 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 |
| Quality of life at day 90 [assessed by the EuroQol - 5 dimension (EQ - 5D) questionnaire] | It is usually represented by a value between 0 and 1, where 1 represents perfect health, 0 represents death, and the intermediate values reflect different degrees of health status. | at 90 days |
| 31171523 | 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. |
| 25678901 | 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. |
| 27581531 | 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. |
| 33865495 | 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. |
| 31603191 | 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. |
| 33686963 | 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. |
| 33749312 | 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. |
| 34708996 | 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. |
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| 28230176 | 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. |
| 26149036 | 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. |
| 38157499 | 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. |
| 23803136 | 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. |
| 22052510 | 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. |
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| 36862407 | 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. |
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| D009422 |
| Nervous System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |