Antiplatelet vs R-tPA for Acute Mild Ischemic Stroke (ARAMIS)

Antiplatelet vs R-tPA for Acute Mild Ischemic Stroke: a Prospective, Random, Blinded Assessment of Outcome and Open Label Multi-center Study

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.

Study Overview

• Status: Completed
• Conditions: Stroke
• Intervention / Treatment: Drug: Aspirin; Drug: Clopidogrel 75mg; Drug: Alteplase

• Study Type: Interventional
• Enrollment (Actual): 760
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • ShenYang, China
    • Lin Tao

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient age ≥18 years;
2. Study treatment can be started within 4.5h;
3. Ischemic stroke confirmed by head CT or MRI;
4. 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;
5. Premorbid mRS ≤ 1;
6. Signed informed consent

Exclusion Criteria:

1. Serious neurological deficits before onset ( mRS ≥ 2)；
2. Obvious head injuries or strokes within 3 months；
3. Subarachnoid hemorrhage;
4. History of intracranial hemorrhage;
5. Intracranial tumor, arteriovenous malformation or aneurysm;
6. Intracranial or spinal cord surgery within 3 months;
7. Arterial puncture at a noncompressible site within the previous seven days;
8. Gastrointestinal or urinary tract hemorrhage within the previous 21 days;
9. Major surgery within 1 month;
10. Systolic pressure ≥180 mmHg or diastolic pressure ≥110 mmHg;
11. Blood glucose < 50 mg/dl (2.7mmol/L);
12. Heparin therapy or oral anticoagulation therapy within 48 hours;
13. Platelet count of <100,000/mm3 (This does not need to be verified prior to randomization if clinical abnormality is not suspected);
14. Oral warfarin is being taken and INR>1.6;
15. Abnormal APTT;
16. Pregnancy;
17. Neurological deficit after epileptic seizures;
18. Myocardial infarction within 3 months;
19. Cerebral infarction with definite anticoagulation indications, such as cerebral infarction caused by cardiogenic embolism;
20. Oral administration is not allowed due to dysphagia;
21. allergy to study drugs;
22. Other serious illness that would confound the clinical outcome at 90 days;
23. Participating in other clinical trials within 3 months;
24. patients not suitable for this clinical studies considered by researcher;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aspirin+ clopidogrel; 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; 100mg qd; Drug: Clopidogrel 75mg; 75mg（after first dose of 300mg）qd
Active Comparator: Alteplase; 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; Iv at 0.9 milligrams per kilogram (mg/kg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of mRS (0-1）	90±7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of mRS (0-2）		90±7 days
occurrence of stroke or other vascular events		90±7 days
proportion of death of any cause		90±7 days
change in NIH Stroke Scale score compared with baseline		24 hours
incidence of early neurological improvement	more than 2 NIH Stroke Scale score decrease compared with baseline	24 hours
Incidence of early neurological deterioration	more than 2 NIH Stroke Scale score increase (not result of cerebral hemorrhage) compared with baseline	7 days
occurrence of symptomatic intracranial hemorrhage	more than 4 NIHSS score increase caused by intracranial hemorrhage	90±7 days
proportion of any bleeding events		90±7 days

Collaborators and Investigators

• Sponsor: General Hospital of Shenyang Military Region

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2018
• Primary Completion (Actual): July 18, 2022
• Study Completion (Actual): July 18, 2022

Study Registration Dates

• First Submitted: September 5, 2018
• First Submitted That Met QC Criteria: September 5, 2018
• First Posted (Actual): September 7, 2018

Study Record Updates

• Last Update Posted (Actual): August 3, 2022
• Last Update Submitted That Met QC Criteria: August 1, 2022
• Last Verified: August 1, 2022

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: k（2018）22-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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