Antiplatelet Therapy in Acute Mild-Moderate Ischemic Stroke

NCT02869009 | Completed Phase 3 DMC

• 1 other identifier: k2016-06
• Study Type: interventional
• Target: 3,000
• Locations: 1 country
• Sites: 1

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.

Conditions

Ischemic Stroke

Keywords

stroke; clopidogrel; antiplatelets

Outcome Measures

Primary Outcomes (1)

• Early neurological deterioration assessed as change of NIHSS

  14 days

Secondary Outcomes (5)

• new clinical vascular events (ischemic stroke/hemorrhagic stroke/TIA/myocardial infarction/vascular death)

  90 days

• Changes in National Institute of Health stroke scale scores

  14 days

• moderate to severe bleeding events

  14 days

• Total mortality

  90 days

• Adverse events/severe adverse events

  90 days

Study Arms (2)

clopidogrel plus aspirin group

EXPERIMENTAL

the group will receive a 300mg loading dose of clopidogrel plus aspirin 100 mg, followed by clopidogrel 75 mg/d and aspirin 100 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.

Drug: clopidogrel; Drug: Aspirin

aspirin group

EXPERIMENTAL

the 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.

Drug: Aspirin

Interventions

clopidogrel DRUG

Also known as: Plavix

clopidogrel plus aspirin group

Aspirin DRUG

aspirin group; clopidogrel plus aspirin group

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• General Hospital of Shenyang Military Region: lead

Study Sites (1)

General Hospital of Shenyang Military Region

Shenyang, Liaoning, China

Location

Related Publications (11)

• 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.

  PMID: 23803136 BACKGROUND

• 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.

  PMID: 20335070 BACKGROUND

• 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.

  PMID: 17931979 BACKGROUND

• 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.

  PMID: 15851601 BACKGROUND

• 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.

  PMID: 16531616 BACKGROUND

• 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.

  PMID: 15276392 BACKGROUND

• Yan HT, Cui Y, Li ZA, Cai JR, Wang Q, Hou XW, Chen HS. Effect of age on the efficacy and safety of clopidogrel plus aspirin vs aspirin alone in acute mild-to-moderate stroke: a secondary analysis of the ATAMIS trial. Front Neurol. 2025 Oct 27;16:1643517. doi: 10.3389/fneur.2025.1643517. eCollection 2025.

  PMID: 41220961 DERIVED

• Cui Y, Wang YH, Kong XR, Chen HS. Early Neurologic Deterioration and Efficacy of Dual Antiplatelet in Anterior Versus Posterior Circulation Stroke. J Am Heart Assoc. 2025 Feb 4;14(3):e037268. doi: 10.1161/JAHA.124.037268. Epub 2025 Jan 23.

  PMID: 39846303 DERIVED

• Cui Y, Liu QY, Chen HS. Dual Antiplatelet Therapy and Outcomes in Acute Mild to Moderate Stroke With Versus Without Large-Artery Atherosclerosis Post Hoc Analysis of ATAMIS. J Am Heart Assoc. 2024 Sep 17;13(18):e036318. doi: 10.1161/JAHA.124.036318. Epub 2024 Sep 9.

  PMID: 39248249 DERIVED

• Chen HS, Cui Y, Wang XH, Ma YT, Han J, Duan YJ, Lu J, Shen LY, Liang Y, Wang WZ, Wang H, Zhao Y, Zhang JT, Song YL, He XM, Li RH, Tao DB, Li J, Huang SM, Wang N, Hong M, Meng C, Zhang W, Wang DL, Nguyen TN; ATAMIS investigators. Clopidogrel Plus Aspirin vs Aspirin Alone in Patients With Acute Mild to Moderate Stroke: The ATAMIS Randomized Clinical Trial. JAMA Neurol. 2024 May 1;81(5):450-460. doi: 10.1001/jamaneurol.2024.0146.

  PMID: 38466274 DERIVED

• 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.

  PMID: 30637134 DERIVED

MeSH Terms

Conditions

Ischemic Stroke; Stroke

Interventions

Clopidogrel; Aspirin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Hui-Sheng Chen

  General Hospital of Shenyang Military Region

  STUDY DIRECTOR

• Xin-Hong Wang

  General Hospital of Shenyang Military Region

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of neurological department

Study Record Dates

• First Submitted: August 1, 2016
• First Posted: August 16, 2016
• Study Start: November 1, 2016
• Primary Completion: October 31, 2022
• Study Completion: October 31, 2022
• Last Updated: December 7, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)