Antiplatelet Therapy in Acute Mild-Moderate Ischemic Stroke

Ischemic Stroke Clinical Trial

— ATAMIS  

Official title:

Antiplatelet Therapy in Acute Mild-Moderate Ischemic Stroke (ATAMIS): a Parallel Randomized, Open-label, Multicenter, Prospective Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02869009
• Other study ID #: k2016-06
• Status: Completed
• Phase: Phase 3
• Start date: November 2016
• Est. completion date: October 31, 2022

Study information

• Verified date: December 2022
• Source: General Hospital of Shenyang Military Region
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3000
• Est. completion date: October 31, 2022
• Est. primary completion date: October 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cerebral Infarction
• Ischemia
• Ischemic Stroke
• Stroke

Intervention

Drug:
• clopidogrel

• Aspirin

Locations

Country	Name	City	State
China	General Hospital of Shenyang Military Region	Shenyang	Liaoning

Sponsors (1)

Lead Sponsor	Collaborator
General Hospital of Shenyang Military Region

Country where clinical trial is conducted

China, 

References & Publications (6)

Bhatt DL, Fox KA, Hacke W, Berger PB, Black HR, Boden WE, Cacoub P, Cohen EA, Creager MA, Easton JD, Flather MD, Haffner SM, Hamm CW, Hankey GJ, Johnston SC, Mak KH, Mas JL, Montalescot G, Pearson TA, Steg PG, Steinhubl SR, Weber MA, Brennan DM, Fabry-Ribaudo L, Booth J, Topol EJ; CHARISMA Investigators. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med. 2006 Apr 20;354(16):1706-17. doi: 10.1056/NEJMoa060989. Epub 2006 Mar 12. — View Citation

Diener HC, Bogousslavsky J, Brass LM, Cimminiello C, Csiba L, Kaste M, Leys D, Matias-Guiu J, Rupprecht HJ; MATCH investigators. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial. Lancet. 2004 Jul 24-30;364(9431):331-7. doi: 10.1016/S0140-6736(04)16721-4. — View Citation

Kennedy J, Hill MD, Ryckborst KJ, Eliasziw M, Demchuk AM, Buchan AM; FASTER Investigators. Fast assessment of stroke and transient ischaemic attack to prevent early recurrence (FASTER): a randomised controlled pilot trial. Lancet Neurol. 2007 Nov;6(11):961-9. doi: 10.1016/S1474-4422(07)70250-8. Epub 2007 Oct 10. — View Citation

Markus HS, Droste DW, Kaps M, Larrue V, Lees KR, Siebler M, Ringelstein EB. Dual antiplatelet therapy with clopidogrel and aspirin in symptomatic carotid stenosis evaluated using doppler embolic signal detection: the Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic Carotid Stenosis (CARESS) trial. Circulation. 2005 May 3;111(17):2233-40. doi: 10.1161/01.CIR.0000163561.90680.1C. Epub 2005 Apr 25. — View Citation

Wang Y, Wang Y, Zhao X, Liu L, Wang D, Wang C, Wang C, Li H, Meng X, Cui L, Jia J, Dong Q, Xu A, Zeng J, Li Y, Wang Z, Xia H, Johnston SC; CHANCE Investigators. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med. 2013 Jul 4;369(1):11-9. doi: 10.1056/NEJMoa1215340. Epub 2013 Jun 26. — View Citation

Wong KS, Chen C, Fu J, Chang HM, Suwanwela NC, Huang YN, Han Z, Tan KS, Ratanakorn D, Chollate P, Zhao Y, Koh A, Hao Q, Markus HS; CLAIR study investigators. Clopidogrel plus aspirin versus aspirin alone for reducing embolisation in patients with acute symptomatic cerebral or carotid artery stenosis (CLAIR study): a randomised, open-label, blinded-endpoint trial. Lancet Neurol. 2010 May;9(5):489-97. doi: 10.1016/S1474-4422(10)70060-0. Epub 2010 Mar 22. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Early neurological deterioration assessed as change of NIHSS		14 days
Secondary	new clinical vascular events (ischemic stroke/hemorrhagic stroke/TIA/myocardial infarction/vascular death)		90 days
Secondary	Changes in National Institute of Health stroke scale scores		14 days
Secondary	moderate to severe bleeding events	cerebral hemorrhage,hemorrhage of digestive tract, or moderate to severe bleeding of other organs.	14 days
Secondary	Total mortality		90 days
Secondary	Adverse events/severe adverse events		90 days