Clinical trial NCT04010955: Adding Antiplatelet During Edoxaban Treatment in Stroke Patients With Non-valvular Atrial Fibrillation (ADD-ON)
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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Acute Ischemic Stroke
Atrial Fibrillation
Extracranial Atherosclerosis
Intracranial Atherosclerosis
Coronary Artery Atherosclerosis
Peripheral Artery Stenosis
Anticoagulant
Antiplatelet
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
Collaborators: name: Samsung Medical Center
name: Myongji Hospital
name: Ewha Womans University
name: Chonbuk National University
name: Pusan National University Hospital
name: Korea University
name: Keimyung University Dongsan Medical Center
name: Chonnam National University Hospital
name: Korea University Guro Hospital
name: Chungnam National University Hospital
name: Chung-Ang University Hosptial, Chung-Ang University College of Medicine
name: Kyungpook National University Hospital
name: Dongtan Sacred Heart Hospital
name: Eulji University Hospital
First posted: 2019-07-08
Enrollment: 1200
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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.

Eligibility 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

Primary outcomes:
measure: MACE (major adverse cardiac event)
timeFrame: 18 months
Secondary outcomes:
measure: Hemorrhagic stroke
timeFrame: 18 months
measure: Stroke
timeFrame: 18 months
measure: Acute Myocardial Infarction
timeFrame: 18 months
measure: Major bleeding
timeFrame: 18 months
measure: Vascular death
timeFrame: 18 months
measure: Ischemic stroke
timeFrame: 18 months
measure: Net clinical benefit based on reduction in major adverse cardiac event compared to major bleeding events
timeFrame: 18 months
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
Study officials:
affiliation: Asan Medical Center
name: Sun U. Kwon, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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