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
Overview
- Phase
- Phase 3
- Intervention
- Aspirin
- Conditions
- Acute Ischemic Stroke
- Sponsor
- Capital Medical University
- Enrollment
- 1184
- Locations
- 71
- Primary Endpoint
- The proportion of patients with a modified Rankin scale (mRS) score of 0-1 at 90-day follow up.
- Status
- Recruiting
- Last Updated
- 4 months ago
Overview
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.
Investigators
Ji Xunming,MD,PhD
Professor
Capital Medical University
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •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.
- •Prior history of moderate or severe ischemic stroke events with residual neurological disability.
- •Pre-stroke mRS score \>
- •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
Arms & Interventions
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.
Intervention: Aspirin
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.
Intervention: Best medical management
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.
Intervention: Placebo
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.
Intervention: Best medical management
Outcomes
Primary Outcomes
The proportion of patients with a modified Rankin scale (mRS) score of 0-1 at 90-day follow up.
Time Frame: 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 Outcomes
- 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 proportion of patients experiencing early neurological deterioration.(Within 24 hours 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 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.)