This is a multicenter, randomized, open-label, blinded-endpoint clinical trial designed to evaluate the efficacy and safety of early administration of eptifibatide following intravenous thrombolysis in patients with acute ischemic stroke who present 4.5 to 24 hours after symptom onset.
Several clinical trials (e.g., TRACE-3, EXPECTS, HOPE) have successfully extended the time window for intravenous thrombolysis (IVT) from the conventional 4.5 hours up to 24 hours after symptom onset by utilizing advanced imaging selection techniques. Consequently, the 2024 Chinese guidelines for reperfusion therapy recommend IVT for patients presenting 4.5 to 24 hours after onset, based on imaging selection criteria. However, clinical practice indicates that a considerable proportion of patients exhibit suboptimal recanalization outcomes or even experience early neurological deterioration (END) despite receiving standard IVT. Previous research, such as the ASSET-IT trial, has primarily focused on patients treated within 4.5 hours of onset. For the growing population of "extended-window" (4.5-24 hours) patients receiving IVT facilitated by advances in imaging, the optimal antiplatelet strategy following thrombolysis remains an area with no high-level evidence. Therefore, this study aims to evaluate the efficacy and safety of early administration of eptifibatide following standard IVT (with tenecteplase or alteplase) in patients with acute ischemic stroke who present 4.5 to 24 hours after symptom onset. Patients who have received standard IVT but exhibit early neurological deterioration, fluctuation, or lack of significant improvement within 1 hour post-thrombolysis will be randomized 1:1 to receive either eptifibatide (a single intravenous bolus followed by a 2-hour infusion) plus standard medical therapy or standard medical therapy alone. The primary efficacy outcome is the proportion of patients achieving an excellent functional outcome (modified Rankin Scale score of 0-1) at 90 days. The primary safety outcome is the incidence of symptomatic intracranial hemorrhage within 48 hours after randomization. A total of 786 participants are planned to be enrolled to detect a 10% absolute difference in the primary outcome with 80% power.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
786
Participants will receive intravenous eptifibatide (135 μg/kg bolus, followed by 0.75 μg/kg/min infusion for 2 hours) initiated within 60 minutes after completion of standard intravenous thrombolysis (either alteplase or tenecteplase). Antiplatelet therapy with aspirin (100 mg) and/or clopidogrel (75 mg) will be administered at 24h after thrombolysis until the follow-up period of 90 days.
Participants will not receive intravenous eptifibatide after completion of standard intravenous thrombolysis. Antiplatelet therapy with aspirin (100 mg) and/or clopidogrel (75 mg) will be administered at 24h after thrombolysis until the follow-up period of 90 days.
Xinqiao Hospital and The Second Affiliated Hospital
Chongqing, Chongqing Municipality, China
The First Affiliated Hospital of Hainan Medical University
Haikou, Hainan, China
Ganzhou People's Hospital
Ganzhou, Jiangxi, China
The First Affiliated Hospital of Gannan Medical University
Ganzhou, Jiangxi, China
Excellent functional outcome
modified Rankin scale score of 0 to 1. modified Rankin scale scores range from 0 to 6, with 0 indicating no disability, 1 no clinically significant disability, 2 slight disability, 3 moderate disability but able to walk unassisted, 4 moderately severe disability, 5 severe disability, and 6 death.
Time frame: 90 days post-randomization
Ordinal degree of disability
Ordinal degree of disability on the modified Rankin scale score at 90 days (shift analysis)
Time frame: 90 days post-randomization
Conversion to Endovascular Therapy
Proportion of patients who converted to endovascular therapy
Time frame: 24 hours post-randomization
Functionally independent
modified Rankin scale score of 0 to 2
Time frame: 90 days post-randomization
Change in NIHSS Score at 48 (±12) Hours
Change in NIHSS score from pre-randomization to 48 (±12) hours
Time frame: 48 (±12) hours post-randomization
Change in NIHSS Score at Discharge or Day 6 (±1)
Change in NIHSS score from pre-randomization to discharge or day 6 (±1)
Time frame: Day 6 (±1) or discharge post-randomization, whichever came first
Health-related quality of life
assessed with the European Quality Five Dimensions Five Level scale
Time frame: 90 days post-randomization
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The Affiliated Hospital of Jinggangshan University
Ji’an, Jiangxi, China
The First Affiliated Hospital of Nanchang University
Nanchang, Jiangxi, China
Symptomatic intracranial hemorrhage
defined as per the Heidelberg bleeding classification
Time frame: 48 (±12) hours post-randomization
Mortality
The proportion of participants who die from any cause within 90 days after randomization in the study
Time frame: 90 days post-randomization
Incidence of major extracranial bleeding within 48 (±12) hours
GUSTO criteria: moderate and severe bleeding
Time frame: 48 (±12) hours post-randomization
Incidence of non-hemorrhagic serious adverse events
Including but not limited to cerebral herniation, pneumonia, respiratory failure, circulatory failure, stress ulcer, secondary epilepsy, urinary tract infection, sepsis, renal failure, acute coronary syndrome, venous thrombosis, and psychiatric symptoms
Time frame: Within 90 days post-randomization