Aspirin Combined With Clopidogrel Versus Intravenous Alteplase for Acute Minor Stroke (AGREE)

Sun Yat-sen University

Status and phase: Not yet enrolling; Phase 4

Conditions: Ischemic Stroke

Treatments: Drug: Clopidogrel; Drug: Alteplase; Drug: Aspirin

Study type: Interventional

Funder types: Other

Identifiers

NCT05910125

SYSKY-2022-252-02

Details and patient eligibility

About

An open-label, blinded endpoint, randomized controlled trial that includes patients diagnosed with non-disabling, non-large vessel occlusion, acute minor stroke within 4.5 hours of onset. Eligible participants would be randomly assigned to the thrombolysis group (intravenous alteplase) and the dual antiplatelet group (oral aspirin plus clopidogrel). The primary outcome is the proportion of the excellent functional outcome (modified Rankin scale 0-1) at 90 days.

Enrollment: 472 estimated patients

Sex: All

Ages: 40 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Aged 40-80 years.
2. Diagnosed with acute ischemic stroke, NIHSS ≤ 5 and single item score ≤ 1 for vision, language, single limb, and no impairment of consciousness.
3. Time from symptoms onset to randomization within 4.5 hours; the onset time refers to the "Last Known Normal" (LKN).
4. Absence of large vessel occlusion on CTA.
5. Pre-stroke mRS ≤ 1.
6. Signed informed consent.

Exclusion criteria

1. Clinically confirmed valvular or non-valvular atrial fibrillation requiring anticoagulation therapy.
2. Intracranial hemorrhage or subarachnoid hemorrhage suggested by CT scan.
3. Acute coronary syndrome suggested by Electrocardiogram.
4. History of gastrointestinal bleeding.
5. Planned sequential IVT or endovascular treatment.
6. History of allergy to aspirin, clopidogrel, and/or alteplase.
7. Systolic blood pressure exceeding 185 mmHg and/or diastolic blood pressure exceeding 110 mmHg despite antihypertensive treatment.
8. Blood glucose ≤ 2.7 mmol/L.
9. Epileptic seizures during a stroke attack.
10. Recent trauma (<15 days).
11. Recent intracranial or spinal cord surgery, head trauma, or stroke (<3 months).
12. History of intracranial hemorrhage, aneurysm, vascular malformation, or brain tumor.
13. Active visceral hemorrhage (<22 days).
14. History of anticoagulant use within 24 hours prior to onset.
15. Platelets <100,000, PTT > 40 seconds on heparin, or PT > 15 or INR > 1.7, or known bleeding disposition.
16. Anticipated life expectancy < 3 months.
17. Pregnant or lactating women.
18. Participation in other clinical trials.
19. Any condition that, in the judgment of the investigator, makes the patient unsuitable for this study or where this study may impose a significant risk to the patient (e.g., inability to understand and/or comply with study procedures and/or follow-up due to psychiatric disorders, cognitive or emotional impairment).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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472 participants in 2 patient groups

DAPT group

Experimental group

Description:

Receiving dual antiplatelet therapy immediately after randomization (Oral aspirin 100mg+clopidogrel 300mg, Day 1). Participants who show no evidence of intracranial hemorrhage on skull CT 24 hours after randomization will receive oral aspirin 100mg/d (Day 2-90) and clopidogrel 75mg/d (Day 2-21), while those with intracranial hemorrhage on skull CT will not receive any antiplatelet drugs.

Treatment:

Drug: Clopidogrel

Drug: Aspirin

IVT group

Active Comparator group

Description:

Receiving intravenous thrombolysis immediately after randomization (Intravenous alteplase, 0.9mg/kg, a maximum dosage of 90mg). Participants who show no evidence of intracranial hemorrhage on skull CT 24 hours after randomization will receive oral aspirin 100mg/d (Day 2-90), while those with intracranial hemorrhage on skull CT will not receive any antiplatelet drugs.

Treatment:

Drug: Alteplase