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

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ClinicalTrials.gov Identifier: NCT04010955
Recruitment Status : Recruiting
First Posted : July 8, 2019
Last Update Posted : October 14, 2019
Sponsor:
Collaborators:
Samsung Medical Center
Myongji Hospital
Ewha Womans University
Chonbuk National University
Pusan National University Hospital
Korea University
Keimyung University Dongsan Medical Center
Chonnam National University Hospital
Korea University Guro Hospital
Chungnam National University Hospital
Chung-Ang University Hosptial, Chung-Ang University College of Medicine
Kyungpook National University Hospital
Dongtan Sacred Heart Hospital
Eulji University Hospital
Information provided by (Responsible Party):
Sun U. Kwon, Asan Medical Center

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.

Condition or disease Intervention/treatment
Acute Ischemic Stroke Atrial Fibrillation Extracranial Atherosclerosis Intracranial Atherosclerosis Coronary Artery Atherosclerosis Peripheral Artery Stenosis Anticoagulant Antiplatelet Drug: Edoxaban Monotherapy

Detailed Description:

Although there is a significant increase in the risk of cerebral infarction in the presence of atrial fibrillation, it is difficult to say that all cerebral infarctions occurring in patients with atrial fibrillation are caused by atrial fibrillation. Carotid stenosis is found in 1/4 of patients with atrial fibrillation, which increases the risk of cerebral infarction. Additional antiplatelet therapy to standard anticoagulation therapy should be considered in some patients. To date, the best medical treatment for prevention of cerebral infarction in patients with atrial fibrillation and accompanying atherosclerosis has not been evaluated yet.

Edoxaban reduced bleeding complication compared to warfarin in patients with atrial fibrillation. In addition, the ENGAGE AF TIMI-48 study showed a tendency to reduce cerebral infarction (p for interaction = 0.08) when administered in combination with one antiplatelet agent and edoxaban. The administration of antiplatelet agents may be due to patients had accompanying myocardial infarction or cerebral infarction. This group is also thought to have a high risk of bleeding due to high HAS-BLED scores. Nonetheless, there was a similar degree of bleeding in patients receiving additional antiplatelet agents. There was also less bleeding in the warfarin arm than in the use of additional antiplatelet agents. (Major bleeding: 0.19 vs 0.24% / yr; intracranial hemorrhage: 0.43 vs 0.57% / yr)

Thus, Edoxaban have good clinical trial results in combination with antiplatelet agents in atrial fibrillation with atherosclerosis compared to other NOACs(new oral anticoagulants). It is also considered to be suitable for combination therapy with antiplatelet agents because of its advantages in different bleeding compared to other warfarin. However, there is no evidence to suggest that Edoxaban alone or in combination with additional antiplatelet agents is better for stroke patients with atrial fibrillation and significant arteriosclerosis.


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Study Type : Observational [Patient Registry]
Estimated Enrollment : 1200 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 18 Months
Official Title: The Role of Additional Antiplatelet Therapy in the Ischemic Stroke With Atrial Fibrillation and Co-morbiD Atherosclerosis During edOxaban treatmeNt. (ADD-ON) Study, Multicenter Registry-based Analysis
Actual Study Start Date : October 1, 2019
Estimated Primary Completion Date : August 31, 2023
Estimated Study Completion Date : February 28, 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Edoxaban

Group/Cohort Intervention/treatment
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
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.
Other Name: Edoxaban and antiplatelet combination

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
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.
Other Name: Edoxaban and antiplatelet combination




Primary Outcome Measures :
  1. MACE (major adverse cardiac event) [ Time Frame: 18 months ]
    Duration for first occurrence of major cardiovascular events after patient registration: ischemic stroke, hemorrhagic stroke, myocardial infarction, vascular death


Secondary Outcome Measures :
  1. Hemorrhagic stroke [ Time Frame: 18 months ]
    Duration for first occurrence of hemorrhagic stroke after patient registration

  2. Stroke [ Time Frame: 18 months ]
    Duration for first occurrence of stroke (ischemic and hemorrhagic) after patient registration

  3. Acute Myocardial Infarction [ Time Frame: 18 months ]
    Duration for first occurrence of acute myocardial infarction after patient registration

  4. Major bleeding [ Time Frame: 18 months ]
    Duration for occurrence of major bleeding based on ISTH( International Society on Thrombosis and Haemostasis) after patient registration

  5. Vascular death [ Time Frame: 18 months ]
    Duration for first occurrence of vascular death after patient registration

  6. Ischemic stroke [ Time Frame: 18 months ]
    Duration for first occurrence of ischemic stroke after patient registration

  7. Net clinical benefit based on reduction in major adverse cardiac event compared to major bleeding events [ Time Frame: 18 months ]
    Net clinical benefit based on reduction in major adverse cardiac event compared to major bleeding events



Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Criteria

Inclusion Criteria:

  1. Patients with acute cerebral infarction or transient ischemic attack within 14 days of symptom onset based on Last Known Normal Time.
  2. Patients with non-valvular atrial fibrillation including paroxysmal atrial fibrillation which is eligible for treatment with Edoxaban.
  3. 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

3) Men and women over 20 years old 4) Patients who voluntarily agreed to register the registry

Exclusion Criteria:

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04010955


Contacts
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Contact: Sun U. Kwon, MD, PhD 82-2-3010-3960 sukwon@amc.seoul.kr

Locations
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Korea, Republic of
Asan Medical Center Recruiting
Seoul, Korea, Republic of, 138-736
Contact: Sun U. Kwon, MD, PhD    82-2-3010-3960    sukwon@amc.seoul.kr   
Sponsors and Collaborators
Asan Medical Center
Samsung Medical Center
Myongji Hospital
Ewha Womans University
Chonbuk National University
Pusan National University Hospital
Korea University
Keimyung University Dongsan Medical Center
Chonnam National University Hospital
Korea University Guro Hospital
Chungnam National University Hospital
Chung-Ang University Hosptial, Chung-Ang University College of Medicine
Kyungpook National University Hospital
Dongtan Sacred Heart Hospital
Eulji University Hospital
Investigators
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Principal Investigator: Sun U. Kwon, MD, PhD Asan Medical Center

Publications:

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Responsible Party: Sun U. Kwon, Professor, Asan Medical Center
ClinicalTrials.gov Identifier: NCT04010955     History of Changes
Other Study ID Numbers: Add-on_001
First Posted: July 8, 2019    Key Record Dates
Last Update Posted: October 14, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Stroke
Intracranial Arteriosclerosis
Atrial Fibrillation
Atherosclerosis
Coronary Artery Disease
Myocardial Ischemia
Ischemia
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Arrhythmias, Cardiac
Heart Diseases
Pathologic Processes
Arteriosclerosis
Arterial Occlusive Diseases
Intracranial Arterial Diseases
Coronary Disease
Edoxaban
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants