Efficacy and Safety of Eptifibatide Therapy Following Intravenous Thrombolysis in Acute Ischemic Stroke Patients Within 4.5 to 24 Hours After Onset: A Multicenter, Randomized Controlled Trial
概览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- Xinqiao Hospital of Chongqing
- 入组人数
- 786
- 试验地点
- 6
- 主要终点
- Excellent functional outcome
概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years.
- •Acute ischemic stroke, with the time interval from last known well to hospital presentation being 4.5 to 24 hours.
- •NIHSS score ≥ 4 before randomization; if large or medium vessel occlusion is present, an NIHSS score ≤ 10 is also required.
- •Presence of any of the following conditions after completion of standard intravenous thrombolysis:
- •No significant neurological improvement within 1 hour (defined as a change in NIHSS score ≤ 1 point from baseline).
- •Early neurological deterioration within 1 hour of onset (defined as an increase in NIHSS score ≥ 2 points from baseline).
- •Neurological fluctuation within 24 hours after symptom onset (defined as an increase in NIHSS score ≥ 2 points from the lowest value post-thrombolysis).
- •Ability to receive the assigned study drug within 60 minutes after intravenous thrombolysis.
- •Signed written informed consent obtained from the patient or their legal representative.
排除标准
- •Intracranial hemorrhage confirmed by CT or MRI.
- •Planned endovascular therapy.
- •Presence of any definite cardioembolic source, including: chronic or paroxysmal atrial fibrillation, sick sinus syndrome, mitral stenosis, mechanical heart valve, endocarditis, intracardiac thrombus or vegetation, myocardial infarction within 3 months, dilated cardiomyopathy, spontaneous echo contrast in the left atrium, or ejection fraction \< 30%.
- •Pre-stroke modified Rankin Scale (mRS) score ≥
- •Renal insufficiency (glomerular filtration rate \< 30 ml/min or serum creatinine \> 220 μmol/L \[2.5 mg/dL\]).
- •Known hypercoagulable state.
- •Platelet count \< 100 × 10⁹/L.
- •Pregnancy or lactation.
- •Allergy to eptifibatide, other glycoprotein IIb/IIIa inhibitors, aspirin, or clopidogrel.
- •History of non-atherosclerotic arteriopathy, including moyamoya disease, arterial dissection, or fibromuscular dysplasia.
研究组 & 干预措施
Eptifibatide (Integrilin)
Participants randomized to this arm 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.
干预措施: Eptifibatide (Integrilin) (Drug)
Standard Medical Therapy
Participants randomized to this arm 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.
干预措施: Standard Medical Therapy (Drug)
结局指标
主要结局
Excellent functional outcome
时间窗: 90 days post-randomization
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.
次要结局
- Ordinal degree of disability(90 days post-randomization)
- Conversion to Endovascular Therapy(24 hours post-randomization)
- Functionally independent(90 days post-randomization)
- Change in NIHSS Score at 48 (±12) Hours(48 (±12) hours post-randomization)
- Change in NIHSS Score at Discharge or Day 6 (±1)(Day 6 (±1) or discharge post-randomization, whichever came first)
- Health-related quality of life(90 days post-randomization)
- Symptomatic intracranial hemorrhage(48 (±12) hours post-randomization)
- Mortality(90 days post-randomization)
- Incidence of major extracranial bleeding within 48 (±12) hours(48 (±12) hours post-randomization)
- Incidence of non-hemorrhagic serious adverse events(Within 90 days post-randomization)
研究者
Zhongming Qiu
Professor
Xinqiao Hospital of Chongqing