Clinical trial NCT06548971: Early Antiplatelet Administration After Intravenous Thrombolysis for Acute Ischemic Stroke (TREND-IVT)
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Acute Ischemic Stroke
Cerebral Infarction
Keywords: Acute ischemic stroke
Intravenous thrombolysis
Early neurological deterioration
Aspirin
Lead sponsor: Capital Medical University
Sponsor class: OTHER
First posted: 2024-08-12
Enrollment: 1184
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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. NIHSS score improvement ≤ 2 points or worsening ≤ 4 points one hour after initiating intravenous thrombolysis compared to pre-thrombolysis.
4. Residual NIHSS score \> 5 points at randomization.
5. Informed consent obtained from patients or their acceptable surrogates.

Exclusion Criteria:

1. Stroke caused by definite large vessel occlusion (including A1 and A2 segments of the anterior cerebral artery, M1 and M2 segments of the middle cerebral artery, P1 and P2 segments of the posterior cerebral artery, intracranial and extracranial segments of the internal carotid artery, basilar artery, and bilateral vertebral artery occlusion) confirmed by imaging (including CTA or MRA).
2. Scheduled for endovascular treatment.
3. Intracranial hemorrhage confirmed by imaging post-thrombolysis.
4. Definite or suspected cardioembolic stroke.
5. Stroke caused by other determined causes, including moyamoya disease, artery dissection, arteritis, etc.
6. Pre-stroke mRS score \> 1.
7. Severe consciousness disturbance with NIHSS item 1a (level of consciousness) ≥ 2 points.
8. Post-thrombolysis imaging indicates an infarct area larger than 1/2 responsible artery supply area.
9. Prior history of stroke events (manifesting as stroke symptoms, including hemorrhagic stroke and ischemic stroke).
10. Known contraindications for antiplatelet therapy, such as coagulation disorders, systemic bleeding, etc.
11. History of aspirin allergy.
12. Use of antiplatelet or anticoagulant therapy within one week pre-stroke.
13. There is definite anticipation of developing indications for anticoagulant therapy during the study period (e.g., atrial fibrillation, mechanical heart valve, deep vein thrombosis, pulmonary embolism, antiphospholipid syndrome, hypercoagulable state).
14. Presence of malignant tumors, chronic hemodialysis, severe renal insufficiency (GFR \< 30 ml/min or serum Cr \> 220 μmol/L (2.5 mg/dl)), severe hepatic insufficiency (serum ALT \> 2 times the upper limit of normal, or serum AST \> 2 times the upper limit of normal), severe heart failure (NYHA class III or IV).
15. Severe non-cardiovascular complications with an expected survival of less than 6 months.
16. Unavailability for follow-up.
17. Presence of dementia, psychiatric disorders, or other known neurological conditions that complicate follow-up.
18. Current participation in another therapeutic study with ongoing treatment and follow-up.
19. Other conditions that are not suitable for participation in this study as determined by the investigator.

Primary outcomes:
measure: The proportion of patients with a modified Rankin scale (mRS) score of 0-1 at 90-day follow up.
timeFrame: Ninety days after stroke.
Secondary outcomes:
measure: The proportion of patients with a modified Rankin scale (mRS) score of 0-1 at 30-day follow up.
timeFrame: Thirty days after stroke.
measure: The proportion of patients with a modified Rankin scale (mRS) score of 0-2 at 90-day follow up.
timeFrame: Ninety days after stroke.
measure: The shift analysis in the 90-day modified Rankin scale (mRS) score.
timeFrame: Ninety days after stroke.
measure: The proportion of patients achieving neurological improvement.
timeFrame: Within 48 hours after stroke.
measure: The proportion of patients experiencing early neurological deterioration.
timeFrame: Within 24 hours after stroke.
measure: The changes in the NIHSS score at 24 hours, 48 hours, and 7 days of enrollment as compared with the baseline.
timeFrame: Within 7 days after stroke.
Other outcomes:
measure: Incidence of symptomatic intracranial hemorrhage.
timeFrame: Within 48 hours after stroke.
measure: Incidence of any intracranial hemorrhage.
timeFrame: Within 48 hours after stroke.
measure: Incidence of systemic hemorrhage.
timeFrame: Within 90 days after stroke.
measure: Incidence of recurrent stroke or other vascular events.
timeFrame: Within 90 days after stroke.
measure: All-cause death.
timeFrame: Within 90 days after stroke.
measure: Incidence of Adverse Events/Serious Adverse Events
timeFrame: Within 90 days after stroke.
Locations:
city: Bengbu
country: China
facility: The Third The People's Hospital Of Bengbu
state: Anhui
city: Beijing
country: China
facility: Xuanwu Hospital, Capital Medical University
state: Beijing
city: Chongqing
country: China
facility: The First Affiliated Hospital of Chongqing Medical and Pharmaceutical College
state: Chongqing
city: Xiamen
country: China
facility: The First Affiliated Hospital Of Xiamen University
state: Fujian
city: Qinzhou
country: China
facility: The Second People's Hospital Of Qinzhou
state: Guangxi
city: Wuzhou
country: China
facility: Wuzhou Red Cross Hospital
state: Guangxi
city: Qiqihar
country: China
facility: The First Hospital Of Qiqihar
state: Heilongjiang
city: Luoyang
country: China
facility: Luoyang Yanshi People's Hospital
state: Henan
city: Zhoukou
country: China
facility: Xihua People's Hospital
state: Henan
city: Liuyang
country: China
facility: Liuyang Jili Hospital
state: Hunan
city: Xiangtan
country: China
facility: Xiangtan Central Hospital
state: Hunan
city: Zhuzhou
country: China
facility: Zhuzhou Central Hospital
state: Hunan
city: Tongliao
country: China
facility: Affiliated Hospital of Inner Mongolia University for the Nationalities
state: Inner Mongolia
city: Ulanqab
country: China
facility: Ulanqab Central Hospital
state: Inner Mongolia
city: Zhalantun
country: China
facility: Zha Lan Tun Shi Zhong Meng Yi Yuan
state: Inner Mongolia
city: Jingdezhen
country: China
facility: Jingdezhen NO.1 People's Hospital
state: Jiangxi
city: Nanchang
country: China
facility: The Second Affiliated Hospital Of Nanchang University
state: Jiangxi
city: Jinan
country: China
facility: Jinan Third People's Hospital
state: Shandong
city: Liaocheng
country: China
facility: The Third People Hospital In Liaocheng
state: Shandong
city: Weihai
country: China
facility: Weihai Municipal Hospital
state: Shandong
city: Leshan
country: China
facility: The People's Hospital Of Leshan
state: Sichuan
city: Shihezi
country: China
facility: Shihezi City People's Hospital
state: Xinjiang
city: Jiaxing
country: China
facility: Haiyan People's Hospital
state: Zhejiang
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.