Early Antiplatelet Administration After Intravenous Thrombolysis for Acute Ischemic Stroke (TREND-IVT)

NCT ID: NCT06548971

Last Updated: 2025-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

1184 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-11-07

Study Completion Date

2026-03-31

Brief Summary

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Stroke is the second leading cause of death worldwide, and ischemic stroke is the most frequent type. Intravenous thrombolysis with recombinant tissue plasminogen activator within 4.5 hours of symptom onset is the most effective therapy for patients with acute ischemic stroke. However, ischemic stroke progression and early reocclusion are not an uncommon phenomenon in patients after intravenous thrombolysis, resulting in neurological deterioration, which is associated with unfavorable functional outcomes. The underlying mechanism mainly involves the augmented platelet activation, triggered by the activated coagulation cascade during thrombolysis, which peaks within 2 hours of initiating rt-PA administration. Therefore, early antiplatelet therapy following intravenous thrombolysis represents a promising therapeutic approach to prevent neurological deterioration and improve the functional outcome of patients treated with intravenous thrombolysis.

Currently, guidelines recommend initiating antiplatelet therapy 24 hours after intravenous thrombolysis due to the potential risk of increased bleeding. The safety and efficacy of early antiplatelet treatment following intravenous thrombolysis in patients with acute ischemic stroke remain clear.

The study aims to test the hypothesis that in patients with acute ischemic stroke treated with intravenous thrombolysis, early administration of oral aspirin will improve functional outcomes without increasing the risk of intracranial hemorrhage.

Detailed Description

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Conditions

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Acute Ischemic Stroke Cerebral Infarction

Keywords

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Acute ischemic stroke Intravenous thrombolysis Early neurological deterioration Aspirin

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Interventional group

Patients in the interventional group will receive early antiplatelet treatment with oral aspirin within 3 hours of initiating intravenous thrombolysis. In addition, the best medical management will be administered according to the guidelines.

Group Type EXPERIMENTAL

Aspirin

Intervention Type DRUG

Patients in the interventional group will chew 300mg of aspirin enteric-coated tablets as soon as possible after randomization. If swallowing difficulties arise, the tablets can be crushed and administered via a nasogastric tube.

Best medical management

Intervention Type OTHER

Patients in both groups will receive the best medical management according to the guidelines.

Control group

Patients in the control group will receive placebos within 3 hours of initiating intravenous thrombolysis. In addition, the best medical management will be administered according to the guidelines.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Patients in the control group will chew 300mg of placebos as soon as possible after randomization. If swallowing difficulties arise, the placebo can be crushed and administered via a nasogastric tube.

Best medical management

Intervention Type OTHER

Patients in both groups will receive the best medical management according to the guidelines.

Interventions

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Aspirin

Patients in the interventional group will chew 300mg of aspirin enteric-coated tablets as soon as possible after randomization. If swallowing difficulties arise, the tablets can be crushed and administered via a nasogastric tube.

Intervention Type DRUG

Placebo

Patients in the control group will chew 300mg of placebos as soon as possible after randomization. If swallowing difficulties arise, the placebo can be crushed and administered via a nasogastric tube.

Intervention Type DRUG

Best medical management

Patients in both groups will receive the best medical management according to the guidelines.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. Age ≥18 years old;
2. Acute ischemic stroke treated with intravenous thrombolysis with alteplase or tenecteplase within 4.5 hours of onset or time last known well, and can receive the study drug treatment within 3 hours of initiating intravenous thrombolysis.
3. Residual NIHSS score \> 5 points assessed 1 hour after initiation of intravenous thrombolysis and prior to randomization.
4. Informed consent obtained from patients or an authorized representative.

Exclusion Criteria

1. Stroke caused by definite large vessel occlusion (including A1/A2 segments of the anterior cerebral artery, M1/M2 segments of the middle cerebral artery, P1/P2 segments of the posterior cerebral artery, intracranial/extracranial segments of the internal carotid artery, basilar artery, and bilateral vertebral artery occlusion) confirmed by vessel imaging (including computed tomography angiography \[CTA\] or magnetic resonance angiography \[MRA\]), or scheduled for endovascular treatment (including mechanical thrombectomy, intra-arterial thrombolysis, and angioplasty).
2. Intracranial hemorrhage confirmed by imaging post-thrombolysis.
3. Definite or suspected cardioembolic stroke.
4. Stroke caused by other determined causes, including nonatherosclerotic vasculopathies (moyamoya disease, artery dissection, arteritis), hypercoagulable states, or hematological disorders.
5. Use of antiplatelet therapy within one week prior to stroke onset, novel anticoagulant drugs within 48 hours prior to stroke onset, or treatment with warfarin with an international normalized ratio (INR)\>1.7.
6. Prior history of moderate or severe ischemic stroke events with residual neurological disability.
7. Pre-stroke mRS score \> 1.
8. Severe consciousness disturbance with NIHSS item 1a (level of consciousness) ≥ 2 points.
9. Post-thrombolysis imaging indicates an infarct area larger than 1/2 responsible artery supply area.
10. Known contraindications for antiplatelet therapy, such as coagulation disorders, or systemic bleeding
11. History of aspirin allergy.
12. Anticipated indications for anticoagulant therapy during the study period (e.g., atrial fibrillation, mechanical heart valve, deep vein thrombosis, pulmonary embolism, antiphospholipid syndrome, hypercoagulable state)
13. Presence of malignant tumors, chronic hemodialysis, severe renal insufficiency (GFR \< 30 mL/min or serum creatinine \> 220 μmol/L \[2.5 mg/dL\]), severe hepatic insufficiency (serum alanine aminotransferase \[ALT\] \>2 times the upper limit of normal, or serum aspartate aminotransferase \[AST\] \>2 times the upper limit of normal), severe heart failure (New York Heart Association \[NYHA\] Functional Classification Class III or IV)
14. Severe non-cardiovascular complications with an expected survival of less than 6 months.
15. Unavailability for follow-up.
16. Presence of dementia, psychiatric disorders, or other known neurological conditions that complicate follow-up.
17. Current participation in another therapeutic study with ongoing treatment and follow-up.
18. Other conditions that make the patient unsuitable for participation in the study as determined by the investigator.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Capital Medical University

OTHER

Sponsor Role lead

Responsible Party

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Ji Xunming,MD,PhD

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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The Third The People's Hospital Of Bengbu

Bengbu, Anhui, China

Site Status RECRUITING

Suzhou municipal hospital

Suzhou, Anhui, China

Site Status RECRUITING

Xuanwu Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Site Status RECRUITING

Aerospace central hospital

Haidian, Beijing Municipality, China

Site Status RECRUITING

Beijing Pinggu District Hospital

Pinggu, Beijing Municipality, China

Site Status RECRUITING

Beijing Luhe Hospital affiliated to Capital Medical University

Tongzhou, Beijing Municipality, China

Site Status RECRUITING

Fujian university affiliated provincial hospital

Fuzhou, Fujian, China

Site Status RECRUITING

The First Affiliated Hospital Of Xiamen University

Xiamen, Fujian, China

Site Status RECRUITING

Xiamen Xinglin hospital

Xiamen, Fujian, China

Site Status NOT_YET_RECRUITING

Zhangzhou Hospital of Fujian Province

Zhangzhou, Fujian, China

Site Status RECRUITING

Brain Hospital Affiliated to Guangzhou Medical University

Guangzhou, Guangdong, China

Site Status NOT_YET_RECRUITING

Guigang people's hospitalv

Guigang, Guangxi, China

Site Status RECRUITING

Wuzhou Red Cross Hospital

Wuzhou, Guangxi, China

Site Status RECRUITING

The Second Affiliated Hospital of Guizhou Medical University

Kaili, Guizhou, China

Site Status RECRUITING

The Second Affiliated Hospital of Hainan Medical University

Haikou, Hainan, China

Site Status RECRUITING

Cangzhou combination of Chinese traditional and western medicine hospital

Cangzhou, Hebei, China

Site Status RECRUITING

Cangzhou Central Hospital

Cangzhou, Hebei, China

Site Status RECRUITING

Hejian city People's Hospital

Cangzhou, Hebei, China

Site Status RECRUITING

Handan Central Hospital

Handan, Hebei, China

Site Status RECRUITING

Handan first hospital

Handan, Hebei, China

Site Status RECRUITING

The First Hospital Of Qiqihar

Qiqihar, Heilongjiang, China

Site Status RECRUITING

Hua county People's Hospital

Anyang, Henan, China

Site Status RECRUITING

Jun county people's hospital

Hebi, Henan, China

Site Status RECRUITING

Jiaozuo Second People's Hospital

Jiangzuo, Henan, China

Site Status RECRUITING

First People's Hospital of Luoyang

Luoyang, Henan, China

Site Status RECRUITING

Luoyang Yanshi People's Hospital

Luoyang, Henan, China

Site Status RECRUITING

Nanyang nanshi hospital

Nanyang, Henan, China

Site Status NOT_YET_RECRUITING

Huanghe Sanmenxia hospital

Sanmenxia, Henan, China

Site Status NOT_YET_RECRUITING

Shangqiu Third People's Hospital

Shangqiu, Henan, China

Site Status RECRUITING

Shangqiu First People's Hospital

Shangqiu, Henan, China

Site Status RECRUITING

Ningling county people's hospital

Shangqucun, Henan, China

Site Status RECRUITING

Xihua People's Hospital

Zhoukou, Henan, China

Site Status RECRUITING

Luyi county people's hospital

Zhoukou, Henan, China

Site Status RECRUITING

Zhumadian Central Hospital

Zhumadian, Henan, China

Site Status RECRUITING

The Third People's Hospital of Hubei Province

Hainan, Hubei, China

Site Status RECRUITING

The First People's Hospital of Changde City

Changde, Hunan, China

Site Status RECRUITING

Changde Taoyuan County People's Hospital

Changde, Hunan, China

Site Status NOT_YET_RECRUITING

Chenzhou first people's hospital

Chenzhou, Hunan, China

Site Status NOT_YET_RECRUITING

Liuyang Jili Hospital

Guankou, Hunan, China

Site Status RECRUITING

Xiangtan Central Hospital

Xiangtan, Hunan, China

Site Status RECRUITING

Zhuzhou Central Hospital

Zhuzhou, Hunan, China

Site Status RECRUITING

Affiliated Hospital of Inner Mongolia University for the Nationalities

Tongliao, Inner Mongolia, China

Site Status RECRUITING

Ulanqab Central Hospital

Ulanqab, Inner Mongolia, China

Site Status RECRUITING

Zha Lan Tun Shi Zhong Meng Yi Yuan

Zhalantun, Inner Mongolia, China

Site Status RECRUITING

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

Site Status RECRUITING

The Fourth Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

Site Status RECRUITING

Jingdezhen NO.1 People's Hospital

Jingdezhen, Jiangxi, China

Site Status RECRUITING

The Second Affiliated Hospital Of Nanchang University

Nanchang, Jiangxi, China

Site Status RECRUITING

Anshan Changda hospital

Anshan, Liaoning, China

Site Status NOT_YET_RECRUITING

Donggang city Central Hospital

Dandong, Liaoning, China

Site Status RECRUITING

Fushun Mining Bureau General Hospital

Fushun, Liaoning, China

Site Status NOT_YET_RECRUITING

Togtoh county hospital

Neimeng, Neimeng, China

Site Status RECRUITING

Dongying people's hospital

Dongying, Shandong, China

Site Status RECRUITING

Shengli oilfield central hospital

Dongying, Shandong, China

Site Status RECRUITING

Shandong province qianfoshan hospital

Jinan, Shandong, China

Site Status RECRUITING

Jinan Third People's Hospital

Jinan, Shandong, China

Site Status RECRUITING

Liaocheng people's hospital

Liaocheng, Shandong, China

Site Status RECRUITING

The Third People Hospital In Liaocheng

Liaocheng, Shandong, China

Site Status RECRUITING

Gaotang county people's hospital

Liaocheng, Shandong, China

Site Status RECRUITING

Pingdu city traditional Chinese medicine hospital

Qingdao, Shandong, China

Site Status RECRUITING

Juxian county people's hospital

Rizhao, Shandong, China

Site Status RECRUITING

Rizhao traditional Chinese medicine hospital

Rizhao, Shandong, China

Site Status RECRUITING

Shandong health group feicheng hospital

Taian, Shandong, China

Site Status RECRUITING

Weihai Municipal Hospital

Weihai, Shandong, China

Site Status RECRUITING

Zibo Central Hospital

Zibo, Shandong, China

Site Status NOT_YET_RECRUITING

Weinan central hospital

Weinan, Shanxi, China

Site Status NOT_YET_RECRUITING

Shenzhen Second People's Hospital

Shenzhen, Shenzhen, China

Site Status RECRUITING

Chengdu Second People's Hospital

Chengdu, Sichuan, China

Site Status RECRUITING

Ya 'an People's Hospital

Ya'an, Sichuan, China

Site Status RECRUITING

Shihezi City People's Hospital

Shihezi, Xinjiang, China

Site Status RECRUITING

Haiyan People's Hospital

Jiaxing, Zhejiang, China

Site Status RECRUITING

Countries

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China

Central Contacts

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XunMing Ji, MD, PD

Role: CONTACT

Phone: 010-8319-9439

Email: [email protected]

Wenbo Zhao, MD, PD

Role: CONTACT

Phone: 010-8319-9048

Email: [email protected]

Facility Contacts

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Bin Ye, M.D.

Role: primary

Lei Zhang

Role: primary

Wenbo Zhao, M.D.

Role: primary

Peifu Wang

Role: primary

Yifei Cheng

Role: primary

Lipeng Cai

Role: primary

Yingchao He

Role: primary

Yihong Zhan, M.D.

Role: primary

Caitang Wu, M.D.

Role: primary

Tingyu Yi

Role: primary

Lixuan Zhan, M.D.

Role: primary

Xinming Li

Role: primary

Xuan Chen, M.D.

Role: primary

Changsong Wu, M.D.

Role: primary

Bin Liu

Role: primary

Yonglin Shan

Role: primary

Zhen Hong, M.D.

Role: primary

Lixin Wu

Role: primary

Shejun Feng

Role: primary

Liping Cheng

Role: primary

Chenghe Sun, M.D.

Role: primary

Hongling Guo

Role: primary

Beihai Jiang

Role: primary

Bo LI

Role: primary

Jinfeng Shi

Role: primary

Yang Zhou, M.D.

Role: primary

Junfeng Shi, M.D.

Role: primary

Meng Xue, M.D.

Role: primary

Yaping Jing

Role: primary

Hong Yang

Role: primary

Zhixiang Sui

Role: primary

Chaoqun Li, M.D.

Role: primary

Hao Liang

Role: primary

Ligong Gao

Role: primary

Fangyan Gong

Role: primary

Jun Wen

Role: primary

Hui Tan, M.D.

Role: primary

Ganghua Feng, M.D.

Role: primary

Yong He, M.D.

Role: primary

Yong Liang, M.D.

Role: primary

Zhen Zhao, M.D.

Role: primary

Yaoming Xu, M.D.

Role: primary

Shuzhen Gong, M.D.

Role: primary

Chengyan Yang, M.D.

Role: primary

Qi Fang

Role: primary

Qi Fang

Role: primary

Mingchao Wu, M.D.

Role: primary

Jianglong Tu, M.D.

Role: primary

Fan Zhang, M.D.

Role: primary

Jing Li

Role: primary

Hong 113012 Zhang, M.D.

Role: primary

Meixiu Hao

Role: primary

Wenjun Zhang

Role: primary

Ye Lang

Role: primary

Weili Li

Role: primary

Peng Guo, M.D.

Role: primary

Weidong Liu

Role: primary

Ke Diao, M.D.

Role: primary

Huqing Li, M.D.

Role: primary

Hong Sui

Role: primary

Jiawen Sun

Role: primary

Lei Mu

Role: primary

Youfeng Si

Role: primary

Weibin Zhong, M.D.

Role: primary

Chao Wang, M.D.

Role: primary

Yahong Guo, M.D.

Role: primary

Pengcheng Fu

Role: primary

Changchuan Wu

Role: primary

Jian Wang

Role: primary

Feng Chen, M.D.

Role: primary

Zhenhua Xi, M.D.

Role: primary

References

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Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B, Jauch EC, Kidwell CS, Leslie-Mazwi TM, Ovbiagele B, Scott PA, Sheth KN, Southerland AM, Summers DV, Tirschwell DL. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2019 Dec;50(12):e344-e418. doi: 10.1161/STR.0000000000000211. Epub 2019 Oct 30.

Reference Type BACKGROUND
PMID: 31662037 (View on PubMed)

Demaerschalk BM, Kleindorfer DO, Adeoye OM, Demchuk AM, Fugate JE, Grotta JC, Khalessi AA, Levy EI, Palesch YY, Prabhakaran S, Saposnik G, Saver JL, Smith EE; American Heart Association Stroke Council and Council on Epidemiology and Prevention. Scientific Rationale for the Inclusion and Exclusion Criteria for Intravenous Alteplase in Acute Ischemic Stroke: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2016 Feb;47(2):581-641. doi: 10.1161/STR.0000000000000086. Epub 2015 Dec 22.

Reference Type BACKGROUND
PMID: 26696642 (View on PubMed)

Wu C, Sun C, Wang L, Lian Y, Xie N, Huang S, Zhao W, Ren M, Wu D, Ding J, Song H, Wang Y, Ma Q, Ji X. Low-Dose Tirofiban Treatment Improves Neurological Deterioration Outcome After Intravenous Thrombolysis. Stroke. 2019 Dec;50(12):3481-3487. doi: 10.1161/STROKEAHA.119.026240. Epub 2019 Oct 1.

Reference Type BACKGROUND
PMID: 31570084 (View on PubMed)

Zinkstok SM, Roos YB; ARTIS investigators. Early administration of aspirin in patients treated with alteplase for acute ischaemic stroke: a randomised controlled trial. Lancet. 2012 Aug 25;380(9843):731-7. doi: 10.1016/S0140-6736(12)60949-0. Epub 2012 Jun 28.

Reference Type BACKGROUND
PMID: 22748820 (View on PubMed)

Zhao W, Li S, Li C, Wu C, Wang J, Xing L, Wan Y, Qin J, Xu Y, Wang R, Wen C, Wang A, Liu L, Wang J, Song H, Feng W, Ma Q, Ji X; TREND Investigators. Effects of Tirofiban on Neurological Deterioration in Patients With Acute Ischemic Stroke: A Randomized Clinical Trial. JAMA Neurol. 2024 Jun 1;81(6):594-602. doi: 10.1001/jamaneurol.2024.0868.

Reference Type BACKGROUND
PMID: 38648030 (View on PubMed)

Other Identifiers

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TREND-IVT

Identifier Type: -

Identifier Source: org_study_id