Adding Antiplatelet During Edoxaban Treatment in Stroke Patients With Non-valvular Atrial Fibrillation (ADD-ON)

NCT04010955 | Active Not Recruiting DMC FDA Drug

• 1 other identifier: Add-on_001
• Study Type: observational
• Target: 1,200
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to compare the effectiveness and safety regarding treatment with standard anticoagulant only or adding antiplatelet to anticoagulant in patients with non-valvular atrial fibrillation and significant atherosclerosis including extracranial, intracranial, coronary or peripheral artery.

Conditions

Acute Ischemic Stroke; Atrial Fibrillation; Extracranial Atherosclerosis; Intracranial Atherosclerosis; Coronary Artery Atherosclerosis; Peripheral Artery Stenosis; Anticoagulant; Antiplatelet

Outcome Measures

Primary Outcomes (1)

• MACE (major adverse cardiac event)

  Duration for first occurrence of major cardiovascular events after patient registration: ischemic stroke, hemorrhagic stroke, myocardial infarction, vascular death

  18 months

Secondary Outcomes (7)

• Hemorrhagic stroke

  18 months

• Stroke

  18 months

• Acute Myocardial Infarction

  18 months

• Major bleeding

  18 months

• Vascular death

  18 months

Study Arms (2)

Edoxaban Monotherapy

edoxaban monotherapy without additional antiplatelet therapy in long term stroke prevention. However, transient additional antiplatelet therapy will be allowed at the discretion of duty physicians.

Drug: Edoxaban Monotherapy

Edoxaban and antiplatelet combination

edoxaban plus additional antiplatelet therapy in long term stroke prevention. However, transient cessation of antiplatelet therapy will be allowed at the discretion of duty physicians.

Drug: Edoxaban Monotherapy

Interventions

Edoxaban Monotherapy DRUG

when the patients will be initially registered in this study, duty physicians will make a decision to give additional antiplatelet therapy in addition to standard edoxaban therapy.

Also known as: Edoxaban and antiplatelet combination

Edoxaban Monotherapy; Edoxaban and antiplatelet combination

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with acute cerebral infarction or transient ischemic attack with non-valvular atrial fibrillation and significant artherosclerosis Significant atherosclerosis means atherosclerosis in the cerebral, coronary or peripheral arteries according to the judgment of the researchers.

You may qualify if:

• Patients with acute cerebral infarction or transient ischemic attack within 14 days of symptom onset based on Last Known Normal Time.
• Patients with non-valvular atrial fibrillation including paroxysmal atrial fibrillation which is eligible for treatment with Edoxaban.
• Patients with significant atherosclerosis confirmed by imaging tests on the cerebral arteries, coronary arteries, or peripheral arteries and suitable for the use of antiplatelet agents.
• Significant intracranial internal stenosis confirmed by CTA or MRA
• A history of coronary artery disease, meaningful findings from CTA or CAG Arterial stenosis
• Peripheral arterial disease (Ankle-Brachial Index, ABI \<0.9, significant stenosis found in lower limb ultrasonography
• \) Men and women over 20 years old 4) Patients who voluntarily agreed to register the registry

You may not qualify if:

• Patients with chronic renal failure (GFR \<30 ml / min) or severe liver damage
• patients requiring warfarin medication due to prosthetic valve replacement
• patients with internal bleeding (active internal bleeding)
• bleeding diathesis
• History of acute myocardial infarction or received coronary artery procedure within 6 months before screening
• Patients who have received or are scheduled to undergo carotid stenting within 1 year
• Currently, two or more antiplatelet agents are required due to arteriosclerosis.
• Patients whose survival period is expected to be less than 12 months due to serious diseases such as terminal cancer or liver failure
• Patients who are scheduled for invasive surgery with possible uncontrolled bleeding, including major surgery
• Women who are pregnant or lactating, do not have contraception during the study
• A person who is found to be unsuitable for participation in the study due to the clinical laboratory test results or other reasons

Sponsors & Collaborators

• Asan Medical Center: lead
• Samsung Medical Center: collaborator
• Myongji Hospital: collaborator
• Ewha Womans University: collaborator
• Chonbuk National University: collaborator
• Pusan National University Hospital: collaborator
• Korea University Ansan Hospital: collaborator
• Keimyung University Dongsan Medical Center: collaborator
• Chonnam National University Hospital: collaborator
• Korea University Guro Hospital: collaborator
• Chungnam National University Hospital: collaborator
• Chung-Ang University Hosptial, Chung-Ang University College of Medicine: collaborator
• Kyungpook National University Hospital: collaborator
• Dongtan Sacred Heart Hospital: collaborator
• Eulji University Hospital: collaborator

Study Sites (1)

Asan Medical Center

Seoul, 138-736, South Korea

Location

Related Publications (15)

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  PMID: 20609686 BACKGROUND

• Willeit K, Pechlaner R, Egger G, Weger S, Oberhollenzer M, Willeit J, Kiechl S. Carotid atherosclerosis and incident atrial fibrillation. Arterioscler Thromb Vasc Biol. 2013 Nov;33(11):2660-5. doi: 10.1161/ATVBAHA.113.302272. Epub 2013 Sep 12.

  PMID: 24030550 BACKGROUND

• Kanter MC, Tegeler CH, Pearce LA, Weinberger J, Feinberg WM, Anderson DC, Gomez CR, Rothrock JF, Helgason CM, Hart RG. Carotid stenosis in patients with atrial fibrillation. Prevalence, risk factors, and relationship to stroke in the Stroke Prevention in Atrial Fibrillation Study. Arch Intern Med. 1994 Jun 27;154(12):1372-7.

  PMID: 8002689 BACKGROUND

• Chang YJ, Ryu SJ, Lin SK. Carotid artery stenosis in ischemic stroke patients with nonvalvular atrial fibrillation. Cerebrovasc Dis. 2002;13(1):16-20. doi: 10.1159/000047740.

  PMID: 11810005 BACKGROUND

• Lehtola H, Airaksinen KEJ, Hartikainen P, Hartikainen JEK, Palomaki A, Nuotio I, Ylitalo A, Kiviniemi T, Mustonen P. Stroke recurrence in patients with atrial fibrillation: concomitant carotid artery stenosis doubles the risk. Eur J Neurol. 2017 May;24(5):719-725. doi: 10.1111/ene.13280. Epub 2017 Mar 20.

  PMID: 28317289 BACKGROUND

• Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007 Jun 19;146(12):857-67. doi: 10.7326/0003-4819-146-12-200706190-00007.

  PMID: 17577005 BACKGROUND

• Chimowitz MI, Lynn MJ, Howlett-Smith H, Stern BJ, Hertzberg VS, Frankel MR, Levine SR, Chaturvedi S, Kasner SE, Benesch CG, Sila CA, Jovin TG, Romano JG; Warfarin-Aspirin Symptomatic Intracranial Disease Trial Investigators. Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis. N Engl J Med. 2005 Mar 31;352(13):1305-16. doi: 10.1056/NEJMoa043033.

  PMID: 15800226 BACKGROUND

• Fisher M. Does the combination of warfarin and aspirin have a place in secondary stroke prevention? No. Stroke. 2009 May;40(5):1944-5. doi: 10.1161/STROKEAHA.108.537670. Epub 2009 Mar 19. No abstract available.

  PMID: 19299634 BACKGROUND

• Kim BJ, Kim HJ, Do Y, Lee JH, Park KY, Cha JK, Kim HY, Kwon JH, Lee KB, Kim DE, Ha SW, Sohn SI, Kwon SU. The impact of prior antithrombotic status on cerebral infarction in patients with atrial fibrillation. J Stroke Cerebrovasc Dis. 2014 Sep;23(8):2054-2059. doi: 10.1016/j.jstrokecerebrovasdis.2014.03.011. Epub 2014 Aug 10.

  PMID: 25113085 BACKGROUND

• Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009 Sep 17;361(12):1139-51. doi: 10.1056/NEJMoa0905561. Epub 2009 Aug 30.

  PMID: 19717844 BACKGROUND

• Kim BJ, Kang HG, Lee DH, Kang DW, Kim JS, Kwon SU. Ischemic stroke on optimal anticoagulation with novel-oral anticoagulants compared with warfarin. Int J Stroke. 2015 Aug;10(6):E68. doi: 10.1111/ijs.12587. No abstract available.

  PMID: 26202718 BACKGROUND

• Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, Waldo AL, Ezekowitz MD, Weitz JI, Spinar J, Ruzyllo W, Ruda M, Koretsune Y, Betcher J, Shi M, Grip LT, Patel SP, Patel I, Hanyok JJ, Mercuri M, Antman EM; ENGAGE AF-TIMI 48 Investigators. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013 Nov 28;369(22):2093-104. doi: 10.1056/NEJMoa1310907. Epub 2013 Nov 19.

  PMID: 24251359 BACKGROUND

• Perez-Gomez F, Alegria E, Berjon J, Iriarte JA, Zumalde J, Salvador A, Mataix L; NASPEAF Investigators. Comparative effects of antiplatelet, anticoagulant, or combined therapy in patients with valvular and nonvalvular atrial fibrillation: a randomized multicenter study. J Am Coll Cardiol. 2004 Oct 19;44(8):1557-66. doi: 10.1016/j.jacc.2004.05.084.

  PMID: 15489085 BACKGROUND

• Ois A, Cuadrado-Godia E, Rodriguez-Campello A, Giralt-Steinhauer E, Jimenez-Conde J, Lopez-Cuina M, Ley M, Soriano C, Roquer J. Relevance of stroke subtype in vascular risk prediction. Neurology. 2013 Aug 6;81(6):575-80. doi: 10.1212/WNL.0b013e31829e6f37. Epub 2013 Jul 3.

  PMID: 23825174 BACKGROUND

• Kang K, Park TH, Kim N, Jang MU, Park SS, Park JM, Ko Y, Lee S, Lee KB, Lee J, Kim DE, Cho YJ, Kim JT, Kim DH, Cha JK, Han MK, Lee JS, Lee J, Oh MS, Choi JC, Lee BC, Hong KS, Bae HJ. Recurrent Stroke, Myocardial Infarction, and Major Vascular Events during the First Year after Acute Ischemic Stroke: The Multicenter Prospective Observational Study about Recurrence and Its Determinants after Acute Ischemic Stroke I. J Stroke Cerebrovasc Dis. 2016 Mar;25(3):656-64. doi: 10.1016/j.jstrokecerebrovasdis.2015.11.036. Epub 2015 Dec 29.

  PMID: 26750575 BACKGROUND

MeSH Terms

Conditions

Ischemic Stroke; Atrial Fibrillation; Intracranial Arteriosclerosis; Coronary Artery Disease

Interventions

edoxaban

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Heart Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Intracranial Arterial Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Myocardial Ischemia

Study Officials

• Sun U. Kwon, MD, PhD

  Asan Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 18 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 24, 2019
• First Posted: July 8, 2019
• Study Start: October 8, 2019
• Primary Completion: June 27, 2025
• Study Completion (Estimated): June 27, 2026
• Last Updated: July 11, 2025

Record last verified: 2025-07

Locations

KR (1)