Early Antiplatelet Administration After Intravenous Thrombolysis for Acute Ischemic Stroke (TREND-IVT)
TREND-IVT
Safety and Efficacy of Treatment With Early Antiplatelet Administration After Intravenous Thrombolysis for Acute Ischemic Stroke (TREND-IVT): A Multicenter, Randomized, Placebo-controlled, Clinical Trial
1 other identifier
interventional
1,184
1 country
71
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Nov 2024
Shorter than P25 for phase_3
71 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 3, 2024
CompletedFirst Posted
Study publicly available on registry
August 12, 2024
CompletedStudy Start
First participant enrolled
November 7, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2026
CompletedDecember 19, 2025
December 1, 2025
1.3 years
August 3, 2024
December 14, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
The proportion of patients with a modified Rankin scale (mRS) score of 0-1 at 90-day follow up.
The mRS ranges from 0 to 6, with higher scores indicating a worse outcome. The primary outcome measure is based on the mRS score, which is dichotomized to define the excellent functional outcome as mRS score of 0-1 at 90-days follow up.
Ninety days after stroke.
Secondary Outcomes (6)
The proportion of patients with a modified Rankin scale (mRS) score of 0-1 at 30-day follow up.
Thirty days after stroke.
The proportion of patients with a modified Rankin scale (mRS) score of 0-2 at 90-day follow up.
Ninety days after stroke.
The shift analysis in the 90-day modified Rankin scale (mRS) score.
Ninety days after stroke.
The proportion of patients achieving neurological improvement.
Within 48 hours after stroke.
The proportion of patients experiencing early neurological deterioration.
Within 24 hours after stroke.
- +1 more secondary outcomes
Other Outcomes (6)
Incidence of symptomatic intracranial hemorrhage.
Within 48 hours after stroke.
Incidence of any intracranial hemorrhage.
Within 48 hours after stroke.
Incidence of systemic hemorrhage.
Within 90 days after stroke.
- +3 more other outcomes
Study Arms (2)
Interventional group
EXPERIMENTALPatients 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.
Control group
PLACEBO COMPARATORPatients 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.
Interventions
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.
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.
Patients in both groups will receive the best medical management according to the guidelines.
Eligibility Criteria
You may qualify if:
- Age ≥18 years old;
- 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.
- Residual NIHSS score \> 5 points assessed 1 hour after initiation of intravenous thrombolysis and prior to randomization.
- Informed consent obtained from patients or an authorized representative.
You may not qualify if:
- 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).
- Intracranial hemorrhage confirmed by imaging post-thrombolysis.
- Definite or suspected cardioembolic stroke.
- Stroke caused by other determined causes, including nonatherosclerotic vasculopathies (moyamoya disease, artery dissection, arteritis), hypercoagulable states, or hematological disorders.
- 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.
- Prior history of moderate or severe ischemic stroke events with residual neurological disability.
- Pre-stroke mRS score \> 1.
- Severe consciousness disturbance with NIHSS item 1a (level of consciousness) ≥ 2 points.
- Post-thrombolysis imaging indicates an infarct area larger than 1/2 responsible artery supply area.
- Known contraindications for antiplatelet therapy, such as coagulation disorders, or systemic bleeding
- History of aspirin allergy.
- 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)
- 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)
- Severe non-cardiovascular complications with an expected survival of less than 6 months.
- Unavailability for follow-up.
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (71)
The Third The People's Hospital Of Bengbu
Bengbu, Anhui, 233000, China
Suzhou municipal hospital
Suzhou, Anhui, 234000, China
Xuanwu Hospital, Capital Medical University
Beijing, Beijing Municipality, 100053, China
Aerospace central hospital
Haidian, Beijing Municipality, 100049, China
Beijing Pinggu District Hospital
Pinggu, Beijing Municipality, 101200, China
Beijing Luhe Hospital affiliated to Capital Medical University
Tongzhou, Beijing Municipality, 101149, China
Fujian university affiliated provincial hospital
Fuzhou, Fujian, 350001, China
The First Affiliated Hospital Of Xiamen University
Xiamen, Fujian, 361003, China
Xiamen Xinglin hospital
Xiamen, Fujian, 361020, China
Zhangzhou Hospital of Fujian Province
Zhangzhou, Fujian, 363000, China
Brain Hospital Affiliated to Guangzhou Medical University
Guangzhou, Guangdong, 510180, China
Guigang people's hospitalv
Guigang, Guangxi, 537100, China
Wuzhou Red Cross Hospital
Wuzhou, Guangxi, 543002, China
The Second Affiliated Hospital of Guizhou Medical University
Kaili, Guizhou, 556099, China
The Second Affiliated Hospital of Hainan Medical University
Haikou, Hainan, 570145, China
Cangzhou combination of Chinese traditional and western medicine hospital
Cangzhou, Hebei, 061001, China
Cangzhou Central Hospital
Cangzhou, Hebei, 061012, China
Hejian city People's Hospital
Cangzhou, Hebei, 062450, China
Handan Central Hospital
Handan, Hebei, 056001, China
Handan first hospital
Handan, Hebei, 056002, China
The First Hospital Of Qiqihar
Qiqihar, Heilongjiang, 161005, China
Hua county People's Hospital
Anyang, Henan, 456400, China
Jun county people's hospital
Hebi, Henan, 458030, China
Jiaozuo Second People's Hospital
Jiangzuo, Henan, 454001, China
First People's Hospital of Luoyang
Luoyang, Henan, 471000, China
Luoyang Yanshi People's Hospital
Luoyang, Henan, 471900, China
Nanyang nanshi hospital
Nanyang, Henan, 473010, China
Huanghe Sanmenxia hospital
Sanmenxia, Henan, 472000, China
Shangqiu Third People's Hospital
Shangqiu, Henan, 476000, China
Shangqiu First People's Hospital
Shangqiu, Henan, 476100, China
Ningling county people's hospital
Shangqucun, Henan, 476700, China
Xihua People's Hospital
Zhoukou, Henan, 466000, China
Luyi county people's hospital
Zhoukou, Henan, 477200, China
Zhumadian Central Hospital
Zhumadian, Henan, 463000, China
The Third People's Hospital of Hubei Province
Hainan, Hubei, 430033, China
The First People's Hospital of Changde City
Changde, Hunan, 415000, China
Changde Taoyuan County People's Hospital
Changde, Hunan, 415099, China
Chenzhou first people's hospital
Chenzhou, Hunan, 424499, China
Liuyang Jili Hospital
Guankou, Hunan, 410300, China
Xiangtan Central Hospital
Xiangtan, Hunan, 411100, China
Zhuzhou Central Hospital
Zhuzhou, Hunan, 412007, China
Affiliated Hospital of Inner Mongolia University for the Nationalities
Tongliao, Inner Mongolia, 028007, China
Ulanqab Central Hospital
Ulanqab, Inner Mongolia, 012000, China
Zha Lan Tun Shi Zhong Meng Yi Yuan
Zhalantun, Inner Mongolia, 162650, China
The First Affiliated Hospital of Soochow University
Suzhou, Jiangsu, 215004, China
The Fourth Affiliated Hospital of Soochow University
Suzhou, Jiangsu, 215021, China
Jingdezhen NO.1 People's Hospital
Jingdezhen, Jiangxi, 333000, China
The Second Affiliated Hospital Of Nanchang University
Nanchang, Jiangxi, 330008, China
Anshan Changda hospital
Anshan, Liaoning, 114000, China
Donggang city Central Hospital
Dandong, Liaoning, 118300, China
Fushun Mining Bureau General Hospital
Fushun, Liaoning, China
Togtoh county hospital
Neimeng, Neimeng, 010200, China
Dongying people's hospital
Dongying, Shandong, 257029, China
Shengli oilfield central hospital
Dongying, Shandong, 257034, China
Shandong province qianfoshan hospital
Jinan, Shandong, 250014, China
Jinan Third People's Hospital
Jinan, Shandong, 250101, China
Liaocheng people's hospital
Liaocheng, Shandong, 252000, China
The Third People Hospital In Liaocheng
Liaocheng, Shandong, 252000, China
Gaotang county people's hospital
Liaocheng, Shandong, 252800, China
Pingdu city traditional Chinese medicine hospital
Qingdao, Shandong, 266700, China
Juxian county people's hospital
Rizhao, Shandong, 276500, China
Rizhao traditional Chinese medicine hospital
Rizhao, Shandong, 276800, China
Shandong health group feicheng hospital
Taian, Shandong, 271614, China
Weihai Municipal Hospital
Weihai, Shandong, 264200, China
Zibo Central Hospital
Zibo, Shandong, 255020, China
Weinan central hospital
Weinan, Shanxi, 714000, China
Shenzhen Second People's Hospital
Shenzhen, Shenzhen, 518035, China
Chengdu Second People's Hospital
Chengdu, Sichuan, 610041, China
Ya 'an People's Hospital
Ya'an, Sichuan, 625000, China
Shihezi City People's Hospital
Shihezi, Xinjiang, 832000, China
Haiyan People's Hospital
Jiaxing, Zhejiang, 314311, China
Related Publications (6)
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.
PMID: 31662037BACKGROUNDDemaerschalk 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.
PMID: 26696642BACKGROUNDWu 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.
PMID: 31570084BACKGROUNDZinkstok 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.
PMID: 22748820BACKGROUNDZhao 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.
PMID: 38648030BACKGROUNDWang J, Li S, Liu L, Ma Q, Li C, Wu C, Wu L, Song H, Ji X, Zhao W. Safety and Efficacy of Early Aspirin Administration After Intravenous Thrombolysis for Acute Ischemic Stroke (TREND-IVT): Rationale and Design of a Multicenter, Randomized, Placebo-Controlled Clinical Trial. J Am Heart Assoc. 2026 Mar 3;15(5):e045180. doi: 10.1161/JAHA.125.045180. Epub 2026 Feb 20.
PMID: 41717940DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor
Study Record Dates
First Submitted
August 3, 2024
First Posted
August 12, 2024
Study Start
November 7, 2024
Primary Completion
March 1, 2026
Study Completion
March 1, 2026
Last Updated
December 19, 2025
Record last verified: 2025-12