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

• ClinicalTrials.gov Identifier: NCT03661411
• Recruitment Status: Completed
• First Posted: September 7, 2018
• Last Update Posted: August 3, 2022
• Sponsor: General Hospital of Shenyang Military Region
• Information provided by (Responsible Party): Hui-Sheng Chen, General Hospital of Shenyang Military Region

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Stroke	Drug: Aspirin; Drug: Clopidogrel 75mg; Drug: Alteplase	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 760 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Antiplatelet vs R-tPA for Acute Mild Ischemic Stroke: a Prospective, Random, Blinded Assessment of Outcome and Open Label Multi-center Study
• Actual Study Start Date: October 17, 2018
• Actual Primary Completion Date: July 18, 2022
• Actual Study Completion Date: July 18, 2022

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures :

1. Proportion of mRS (0-1） [ Time Frame: 90±7 days ]

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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;

Contacts and Locations

Locations

China

Lin Tao

ShenYang, China

Sponsors and Collaborators

General Hospital of Shenyang Military Region

Investigators

• Study Chair: Huisheng Chen, Doctor; Neurology Department

More Information

• Responsible Party: Hui-Sheng Chen, Director, General Hospital of Shenyang Military Region
• ClinicalTrials.gov Identifier: NCT03661411
• Other Study ID Numbers: k（2018）22-1
• First Posted: September 7, 2018
• Last Update Posted: August 3, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Stroke; Ischemic Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Aspirin; Tissue Plasminogen Activator; Clopidogrel; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents