Clinical trial NCT02869009: Antiplatelet Therapy in Acute Mild-Moderate Ischemic Stroke
Official title: Antiplatelet Therapy in Acute Mild-Moderate Ischemic Stroke (ATAMIS): a Parallel Randomized, Open-label, Multicenter, Prospective Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ischemic Stroke
Keywords: stroke
clopidogrel
antiplatelets
Lead sponsor: General Hospital of Shenyang Military Region
Sponsor class: OTHER
First posted: 2016-08-16
Enrollment: 3000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The risk of early recurrence or progression of acute ischemic stroke is very high, even in patients treated with aspirin. The Chance study show that clopidogrel plus aspirin treatment reduced the risk of recurrent stroke in patients with transient ischemic attack (TIA) or minor ischemic stroke (NIHSS ≤ 3) within 24 hour onset and was not associated with increased hemorrhage events, compared with aspirin monotherapy. However, it is not known whether the dual antiplatelet treatment could reduce the risk of early recurrence or progression in patients with acute mild to moderate ischemic stroke (4 ≤ NIHSS ≤ 10). The investigators hypothesise that clopidogrel-aspirin treatment will be superior to aspirin monotherapy in this group of patients.

Detailed description: The ATAMIS study is a multicentre, prospective, randomised, open-label, controlled trial with a target enrollment of 3,000 patients from 60 centres of the Northeast China. Eligible patients are as follows: (1) definite acute ischemic stroke; (2) neurological deficit: 4 ≤ NIHSS ≤ 10; (3) time from onset to drug treatment: within 48 hours.

Patients in the clopidogrel-aspirin group will receive a 300mg loading dose of clopidogrel, followed by clopidogrel 75 mg/d and aspirin 75 mg/d from day 2 to day 14, and followed by clopidogrel 75 mg/d or aspirin 100 mg/d from day 15 to day 90.

Patients in the aspirin-alone group will receive 100-300 mg aspirin from day 1 to day 14, followed by aspirin 100 mg/d from day 15 to day 90.

The primary efficacy end point is early neurological deterioration assessed as a change of NIHSS: no change of NIHSS within 14 days.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* Acute ischemic stroke that can be randomized within 48 hours of symptoms onset
* neurological deficit: 4 ≤ NIHSS ≤ 10
* CT or MRI scan ruling out hemorrhage or other pathology
* the first onset of ischemic stroke or previous stroke with no obvious sequelae (mRS≤1)
* Signed informed consent by patient self or legally authorized representatives

Exclusion Criteria:

* intracranial hemorrhage and hemorrhagic cerebral infarction
* Thrombolysis for ischemic stroke
* Allergy to clopidogrel and/or aspirin
* History of stroke with serious sequelae
* Severe systemic disease (such as severe infection, severe hepatic and renal dysfunction)
* Clear indication for anticoagulation (atrial fibrillation, mechanical cardiac valves, deep venous thrombosis, pulmonary embolism)
* History of intracranial hemorrhage
* Planned treatment with nonsteroidal anti-inflammatory drugs to affect platelet function
* Anticoagulation within 10 days
* Gastrointestinal bleed or major surgery within 3 months
* Planned or likely revascularization (any angioplasty or vascular surgery) within the next 3 months
* Planned surgery or intervention to stop antiplatelet therapy
* Ischemic stroke induced by angiography or surgery
* Pregnancy or childbirth within the previous 4 weeks
* Patients who have been treated with any other investigational drug within 3 months of enrollment
* Severe noncardiovascular comorbidity with life expectancy \<3 months

Primary outcomes:
measure: Early neurological deterioration assessed as change of NIHSS
timeFrame: 14 days
Secondary outcomes:
measure: new clinical vascular events (ischemic stroke/hemorrhagic stroke/TIA/myocardial infarction/vascular death)
timeFrame: 90 days
measure: Changes in National Institute of Health stroke scale scores
timeFrame: 14 days
measure: moderate to severe bleeding events
timeFrame: 14 days
measure: Total mortality
timeFrame: 90 days
measure: Adverse events/severe adverse events
timeFrame: 90 days
Other outcomes:
Locations:
city: Shenyang
country: China
facility: General Hospital of Shenyang Military Region
state: Liaoning
Study officials:
affiliation: General Hospital of Shenyang Military Region
name: Hui-Sheng Chen
role: STUDY_DIRECTOR
affiliation: General Hospital of Shenyang Military Region
name: Xin-Hong Wang
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Hou X, Li X, Wang X, Chen H. Antiplatelet Therapy in Acute Mild-Moderate Ischemic Stroke (ATAMIS): a parallel, randomised, open-label, multicentre, prospective study. Stroke Vasc Neurol. 2018 Sep 23;3(4):263-267. doi: 10.1136/svn-2018-000148. eCollection 2018 Dec.