Acute Ischemic Stroke, Cerebral Infarction
Conditions
Keywords
Acute ischemic stroke, Intravenous thrombolysis, Early neurological deterioration, Aspirin
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.
Interventions
DRUGAspirin
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.
DRUGPlacebo
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.
Sponsors
Capital Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Incidence of symptomatic intracranial hemorrhage. | Within 48 hours after stroke. | Symptomatic intracranial hemorrhage is defined as the demonstration of hemorrhage within brain parenchyma on head imaging leading to an increase of at least 4 points in the NIHSS score, according to the criteria of the European Cooperative Acute Stroke Study III (ECASS III). |
| Incidence of any intracranial hemorrhage. | Within 48 hours after stroke. | Any intracranial hemorrhage is defined as the demonstration of hemorrhage within brain parenchyma on head imaging, according to the criteria of the ECASS III. |
| Incidence of recurrent stroke or other vascular events. | Within 90 days after stroke. | The incidence of recurrent stroke or other vascular events (including hemorrhagic and ischemic stroke, myocardial infarction, and cardiovascular death) within 90 days of randomization. |
| All-cause death. | Within 90 days after stroke. | The incidence of death events at any time from randomization through day 90. |
| Incidence of Adverse Events/Serious Adverse Events | Within 90 days after stroke. | The incidence of other adverse events and serious adverse events at any time from randomization through day 90. |
| Incidence of systemic hemorrhage. | Within 90 days after stroke. | The incidence of systemic hemorrhage at any time from randomization through day 90, according to the criteria of the GUSTO. |
Countries
China
Contacts
Primary ContactXunMing Ji, MD, PD
Backup ContactWenbo Zhao, MD, PD
Outcome results
None listed