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

Phase 3
Recruiting
Conditions
Acute Ischemic Stroke
Cerebral Infarction
Interventions
Drug: Placebo
Other: Best medical management
Registration Number
NCT06548971
Lead Sponsor
Capital Medical University
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
1184
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Interventional groupAspirinPatients 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.
Interventional groupBest medical managementPatients 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 groupPlaceboPatients 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.
Control groupBest medical managementPatients 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.
Primary Outcome Measures
NameTimeMethod
The proportion of patients with a modified Rankin scale (mRS) score of 0-1 at 90-day follow up.Ninety days after stroke.

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.

Secondary Outcome Measures
NameTimeMethod
The proportion of patients with a modified Rankin scale (mRS) score of 0-1 at 30-day follow up.Thirty days after stroke.

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 30-days follow up.

The proportion of patients with a modified Rankin scale (mRS) score of 0-2 at 90-day follow up.Ninety days after stroke.

The mRS ranges from 0 to 6, with higher scores indicating a worse outcome. Functional independence is defined as mRS of 0-2.

The proportion of patients experiencing early neurological deterioration.Within 24 hours after stroke.

Early neurological deterioration is defined as an increase of ≥4 points in the NIHSS score within 24 hours of randomization compared with the minimum NIHSS score before deterioration.

The shift analysis in the 90-day modified Rankin scale (mRS) score.Ninety days after stroke.

The mRS ranges from 0 to 6, with higher scores indicating a worse outcome.

The proportion of patients achieving neurological improvement.Within 48 hours after stroke.

Neurological improvement is defined as a decrease of ≥2 points in the NIHSS score at 48 hours of randomization compared to baseline assessment.

The changes in the NIHSS score at 24 hours, 48 hours, and 7 days of enrollment as compared with the baseline.Within 7 days after stroke.

The NIHSS ranges from 0 to 42 points, with higher scores indicating worse neurological deficits.

Trial Locations

Locations (23)

The Third The People's Hospital Of Bengbu

🇨🇳

Bengbu, Anhui, China

Xuanwu Hospital, Capital Medical University

🇨🇳

Beijing, Beijing, China

The First Affiliated Hospital of Chongqing Medical and Pharmaceutical College

🇨🇳

Chongqing, Chongqing, China

The First Affiliated Hospital Of Xiamen University

🇨🇳

Xiamen, Fujian, China

The Second People's Hospital Of Qinzhou

🇨🇳

Qinzhou, Guangxi, China

Wuzhou Red Cross Hospital

🇨🇳

Wuzhou, Guangxi, China

The First Hospital Of Qiqihar

🇨🇳

Qiqihar, Heilongjiang, China

Luoyang Yanshi People's Hospital

🇨🇳

Luoyang, Henan, China

Xihua People's Hospital

🇨🇳

Zhoukou, Henan, China

Liuyang Jili Hospital

🇨🇳

Liuyang, Hunan, China

Xiangtan Central Hospital

🇨🇳

Xiangtan, Hunan, China

Zhuzhou Central Hospital

🇨🇳

Zhuzhou, Hunan, China

Affiliated Hospital of Inner Mongolia University for the Nationalities

🇨🇳

Tongliao, Inner Mongolia, China

Ulanqab Central Hospital

🇨🇳

Ulanqab, Inner Mongolia, China

Zha Lan Tun Shi Zhong Meng Yi Yuan

🇨🇳

Zhalantun, Inner Mongolia, China

Jingdezhen NO.1 People's Hospital

🇨🇳

Jingdezhen, Jiangxi, China

The Second Affiliated Hospital Of Nanchang University

🇨🇳

Nanchang, Jiangxi, China

Jinan Third People's Hospital

🇨🇳

Jinan, Shandong, China

The Third People Hospital In Liaocheng

🇨🇳

Liaocheng, Shandong, China

Weihai Municipal Hospital

🇨🇳

Weihai, Shandong, China

The People's Hospital Of Leshan

🇨🇳

Leshan, Sichuan, China

Shihezi City People's Hospital

🇨🇳

Shihezi, Xinjiang, China

Haiyan People's Hospital

🇨🇳

Jiaxing, Zhejiang, China

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