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

Aspirin Combined With Clopidogrel Versus Intravenous Alteplase for Acute Minor Stroke: An Open-label, Blinded Endpoint, Randomized Controlled Trial

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Ischemic Stroke
• Intervention / Treatment: Drug: Alteplase; Drug: Aspirin; Drug: Clopidogrel

• Study Type: Interventional
• Enrollment (Estimated): 472
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Yamei Tang; Phone Number: 86-20-81332619; Email: tangym@mail.sysu.edu.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DAPT group; 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.	Drug: Aspirin; See arm/group descriptions.; Drug: Clopidogrel; See arm/group descriptions.
Active Comparator: IVT group; 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.	Drug: Alteplase; See arm/group descriptions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The modified Rankin Scale score (mRS) 0-1	The proportion of the modified Rankin Scale score (mRS) 0-1 at 90 days.	90(±7) days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The modified Rankin Scale score (mRS) 0-1	The proportion of the modified Rankin Scale score (mRS) 0-1 at 7 days or discharge (whichever occurred first).	7(±1) days
Early neurological deterioration	The incidence of early neurological deterioration at 7 days.	7(±1) days
Recurrent stroke	The incidence of recurrent stroke at 90 days.	90(±7) days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
SAFETY OUTCOME: Symptomatic intracranial hemorrhage	Symptomatic intracranial hemorrhage within 36 hours (according to Heidelberg criteria)	24 (±12) hours
SAFETY OUTCOME: Mortality	Mortality at 90 days	90(±7) days
SAFETY OUTCOME: Any intracranial hemorrhage	Any intracranial hemorrhage within 36 hours (according to Heidelberg criteria)	24 (±12) hours

Collaborators and Investigators

• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Investigators: Principal Investigator: Yamei Tang, Sun Yat-sen Memorial Hospital，Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2023
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: June 11, 2023
• First Submitted That Met QC Criteria: June 11, 2023
• First Posted (Estimated): June 19, 2023

Study Record Updates

• Last Update Posted (Estimated): June 19, 2023
• Last Update Submitted That Met QC Criteria: June 11, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Aspirin; Clopidogrel; Tissue Plasminogen Activator
• Other Study ID Numbers: SYSKY-2022-252-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No