Antiplatelet vs R-tPA for Acute Mild Ischemic Stroke

NCT03661411 | Completed Phase 4 DMC

• 1 other identifier: k（2018）22-1
• Study Type: interventional
• Target: 760
• Locations: 1 country
• Sites: 1

Brief Summary

Acute ischemic stroke (AIS) is one of common diseases with significant morbidity, mortality and disability. A wide array of studies confirms that intravenous thrombolytic therapy with alteplase can effectively improve the functional prognosis in acute ischemic stroke. Thus all guidelines recommended the intravenous thrombolytic therapy with alteplase for acute ischemic stroke within 4.5 hours from stroke onset. Minor stroke is usually defined as NIHSS score ≤ 3 or 5，although it accounts for 1/2-2/3 of AIS, the evidence of thrombolysis is insufficient. A study from Canada shows that 28.5% of patients with minor stroke who have not receive rt-pa thrombolytic therapy are unable to walk independently when discharged. Based on such a consideration,the PRISMS study further compares the efficacy and safety of thrombolytic therapy with antithrombotic therapy in patients with minor stroke. Unfortunately, the study has been early terminated due to the sponsorship reason in 2018, with only 313 cases enrolled. The preliminary results shows that there is no significant difference of the 90-day neurological function between the two groups, while the safety of the treatment group with alteplase has a higher rate of symptomatic intracranial hemorrhage. The patient receiving thrombolysis can not be given antithrombolytic therapy within 24 hours even if the patient's condition has worsened, is clinically more puzzling. The CHANCE study in 2013 shows that the efficacy of aspirin with clopidogrel is superior to aspirin alone with minor stroke (NIHSS \< 3) or TIA(ABCD2 \< 4). The POINT study in 2018 further confirmed the efficacy and safety of intensive antithrombotic therapy within 12 hours of onset with minor stroke. Based on the above discussion, this study aims to explore the efficacy and safety of aspirin with clopidogrel vs alteplase in the treatment of acute minor stroke.

Conditions

Stroke

Outcome Measures

Primary Outcomes (1)

• Proportion of mRS (0-1）

  90±7 days

Secondary Outcomes (8)

• Proportion of mRS (0-2）

  90±7 days

• change in NIH Stroke Scale score compared with baseline

  24 hours

• incidence of early neurological improvement

  24 hours

• Incidence of early neurological deterioration

  7 days

• occurrence of stroke or other vascular events

  90±7 days

Study Arms (2)

Aspirin+ clopidogrel

EXPERIMENTAL

aspirin 100mg qd and clopidogrel 75mg（300mg in the first day）qd with a total of 10-14 days, then oral aspirin 100mg or clopidogrel 75mg qd lasting for 90 days.

Drug: Aspirin; Drug: Clopidogrel 75mg

Alteplase

ACTIVE COMPARATOR

intravenous alteplase (0.9 mg/kg and maximal dose of 90 mg) was given, and followed by antithrombotic protocol 24 hours after thrombolysis based on clinical guideline.

Drug: Alteplase

Interventions

Aspirin DRUG

100mg qd

Aspirin+ clopidogrel

Clopidogrel 75mg DRUG

75mg（after first dose of 300mg）qd

Aspirin+ clopidogrel

Alteplase DRUG

Iv at 0.9 milligrams per kilogram (mg/kg)

Alteplase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient age ≥18 years;
• Study treatment can be started within 4.5h;
• Ischemic stroke confirmed by head CT or MRI;
• NIHSS score ≤ 5, and ≤ 1 NIHSS score in single item scores such as vision, language, neglect and single limb and no score in consciousness item;
• Premorbid mRS ≤ 1;
• Signed informed consent

You may not qualify if:

• Serious neurological deficits before onset ( mRS ≥ 2)；
• Obvious head injuries or strokes within 3 months；
• Subarachnoid hemorrhage;
• History of intracranial hemorrhage;
• Intracranial tumor, arteriovenous malformation or aneurysm;
• Intracranial or spinal cord surgery within 3 months;
• Arterial puncture at a noncompressible site within the previous seven days;
• Gastrointestinal or urinary tract hemorrhage within the previous 21 days;
• Major surgery within 1 month;
• Systolic pressure ≥180 mmHg or diastolic pressure ≥110 mmHg;
• Blood glucose \< 50 mg/dl (2.7mmol/L);
• Heparin therapy or oral anticoagulation therapy within 48 hours;
• Platelet count of \<100,000/mm3 (This does not need to be verified prior to randomization if clinical abnormality is not suspected);
• Oral warfarin is being taken and INR\>1.6;
• Abnormal APTT;

Sponsors & Collaborators

• General Hospital of Shenyang Military Region: lead

Study Sites (1)

Lin Tao

Shenyang, China

Location

Related Publications (7)

• Yao ZG, Pei YF, Chen HS. Onset to Treatment Time and Early Neurological Deterioration of Dual Antiplatelet Therapy Versus Alteplase in Minor Stroke. J Am Heart Assoc. 2025 Nov 4;14(21):e043980. doi: 10.1161/JAHA.125.043980. Epub 2025 Oct 23.

  PMID: 41128284 DERIVED

• Fei ZX, Yin Y, Cui Y, Nguyen TN, Chen HS. Dual Antiplatelet Therapy Versus Alteplase for Mild Stroke with Admission NIHSS Score 0-3 Versus 4-5: A Secondary Analysis of the ARAMIS Randomized Trial. CNS Drugs. 2025 Oct;39(10):1037-1046. doi: 10.1007/s40263-025-01211-6. Epub 2025 Aug 4.

  PMID: 40760234 DERIVED

• He XY, He C, Chen HS. Renal function and efficacy of dual antiplatelet vs. alteplase in minor stroke: a post hoc analysis of ARAMIS study. Front Neurol. 2025 Apr 30;16:1568711. doi: 10.3389/fneur.2025.1568711. eCollection 2025.

  PMID: 40371069 DERIVED

• Cui Y, Chen HS. Dual antiplatelet versus alteplase in anterior and posterior circulation minor stroke. Stroke Vasc Neurol. 2025 Aug 26;10(4):491-498. doi: 10.1136/svn-2024-003705.

  PMID: 39663175 DERIVED

• Cui Y, He C, Li ZA, Wang Y, Chen HS. Dual Antiplatelet Versus Alteplase for Early Neurologic Deterioration in Minor Stroke With Versus Without Large Vessel Occlusion: Prespecified Post Hoc Analysis of the ARAMIS Trial. Stroke. 2024 Nov;55(11):2590-2598. doi: 10.1161/STROKEAHA.124.048248. Epub 2024 Oct 10.

  PMID: 39387110 DERIVED

• Cui Y, Zhao ZA, Wang JQ, Qiu SQ, Shen XY, Li ZY, Hu HZ, Chen HS. Systolic blood pressure and early neurological deterioration in minor stroke: A post hoc analysis of ARAMIS trial. CNS Neurosci Ther. 2024 Jul;30(7):e14868. doi: 10.1111/cns.14868.

  PMID: 39014552 DERIVED

• Chen HS, Cui Y, Zhou ZH, Zhang H, Wang LX, Wang WZ, Shen LY, Guo LY, Wang EQ, Wang RX, Han J, Dong YL, Li J, Lin YZ, Yang QC, Zhang L, Li JY, Wang J, Xia L, Ma GB, Lu J, Jiang CH, Huang SM, Wan LS, Piao XY, Li Z, Li YS, Yang KH, Wang DL, Nguyen TN; ARAMIS Investigators. Dual Antiplatelet Therapy vs Alteplase for Patients With Minor Nondisabling Acute Ischemic Stroke: The ARAMIS Randomized Clinical Trial. JAMA. 2023 Jun 27;329(24):2135-2144. doi: 10.1001/jama.2023.7827.

  PMID: 37367978 DERIVED

MeSH Terms

Conditions

Stroke

Interventions

Aspirin; Clopidogrel; Tissue Plasminogen Activator

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors

Study Officials

• Huisheng Chen, Doctor

  Neurology Department

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: September 5, 2018
• First Posted: September 7, 2018
• Study Start: October 17, 2018
• Primary Completion: July 18, 2022
• Study Completion: July 18, 2022
• Last Updated: August 3, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)