Acute Ischemic Stroke
Conditions
Keywords
Acute Ischemic Stroke, Intravenous thrombolysis, Eptifibatide, Neurological deterioration
Brief summary
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.
Detailed description
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.
Interventions
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.
DRUGStandard Medical Therapy
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.
Sponsors
Xinqiao Hospital of Chongqing
The First Affiliated Hospital of Hainan Medical College
The First Affiliated Hospital of Nanchang University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years. 2. Acute ischemic stroke, with the time interval from last known well to hospital presentation being 4.5 to 24 hours. 3. NIHSS score ≥ 4 before randomization; if large or medium vessel occlusion is present, an NIHSS score ≤ 10 is also required. 4. Presence of any of the following conditions after completion of standard intravenous thrombolysis: 1. No significant neurological improvement within 1 hour (defined as a change in NIHSS score ≤ 1 point from baseline). 2. Early neurological deterioration within 1 hour of onset (defined as an increase in NIHSS score ≥ 2 points from baseline). 3. Neurological fluctuation within 24 hours after symptom onset (defined as an increase in NIHSS score ≥ 2 points from the lowest value post-thrombolysis). 5. Ability to receive the assigned study drug within 60 minutes after intravenous thrombolysis. 6. Signed written informed consent obtained from the patient or their legal representative.
Exclusion criteria
1. Intracranial hemorrhage confirmed by CT or MRI. 2. Planned endovascular therapy. 3. 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%. 4. Pre-stroke modified Rankin Scale (mRS) score ≥ 2. 5. Renal insufficiency (glomerular filtration rate \< 30 ml/min or serum creatinine \> 220 μmol/L \[2.5 mg/dL\]). 6. Known hypercoagulable state. 7. Platelet count \< 100 × 10⁹/L. 8. Pregnancy or lactation. 9. Allergy to eptifibatide, other glycoprotein IIb/IIIa inhibitors, aspirin, or clopidogrel. 10. History of non-atherosclerotic arteriopathy, including moyamoya disease, arterial dissection, or fibromuscular dysplasia. 11. Pre-existing neurological or psychiatric disease that would preclude accurate neurological assessment. 12. History of bleeding diathesis, severe cardiac disease, liver disease, or sepsis. 13. Brain tumor with mass effect on imaging (except for small meningiomas). 14. Evidence of intracranial arteriovenous malformation or aneurysm with diameter \> 5 mm on CT or MR angiography. 15. Current participation in another clinical trial. 16. Any terminal illness with life expectancy \< 6 months. 17. Anticipated inability to complete follow-up.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Excellent functional outcome | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ordinal degree of disability | 90 days post-randomization | Ordinal degree of disability on the modified Rankin scale score at 90 days (shift analysis) |
| Conversion to Endovascular Therapy | 24 hours post-randomization | Proportion of patients who converted to endovascular therapy |
| Functionally independent | 90 days post-randomization | modified Rankin scale score of 0 to 2 |
| Change in NIHSS Score at 48 (±12) Hours | 48 (±12) hours post-randomization | Change in NIHSS score from pre-randomization to 48 (±12) hours |
| Change in NIHSS Score at Discharge or Day 6 (±1) | Day 6 (±1) or discharge post-randomization, whichever came first | Change in NIHSS score from pre-randomization to discharge or day 6 (±1) |
| Health-related quality of life | 90 days post-randomization | assessed with the European Quality Five Dimensions Five Level scale |
| Symptomatic intracranial hemorrhage | 48 (±12) hours post-randomization | defined as per the Heidelberg bleeding classification |
| Mortality | 90 days post-randomization | The proportion of participants who die from any cause within 90 days after randomization in the study |
| Incidence of major extracranial bleeding within 48 (±12) hours | 48 (±12) hours post-randomization | GUSTO criteria: moderate and severe bleeding |
| Incidence of non-hemorrhagic serious adverse events | Within 90 days post-randomization | 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 |
Countries
China
Contacts
CONTACTWei Li, MD
CONTACTJing Lin, MD
PRINCIPAL_INVESTIGATORZhongming Qiu, MD
Xinqiao Hospital of the Army Medical University
PRINCIPAL_INVESTIGATORZhenqiang Zhao, MD
The First Affiliated Hospital of Hainan Medical University
PRINCIPAL_INVESTIGATORDaojun Hong, MD
The First Affiliated Hospital of Nanchang University
Outcome results
None listed