The Efficacy and Safety of Non-vItamiN K antaGonist oraL Anticoagulants for intermEdiate Stroke Risk in Patients With Atrial Fibrillation (SINGLE-AF)

Study Overview
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Brief Summary
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The purpose of this study is to investigate the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOAC) in atrial fibrillation patients with intermediate stroke risk (CHA2DS2-VASc score 1 for male, 2 for female). A. Major safety results include major bleeding and clinically relevant non-major bleeding. B. Major efficacy results include strokes, systemic embolism and mortality. C. Other results include myocardial infarction, pulmonary embolism, transient ischemic attack, hospitalization, drug compliance, quality of life questionnaire (AFEQT), cognitive function (KDSQ), aging questionnaire(K-Frail) and hand grip strength.

Official Title
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The Efficacy and Safety of Non-vItamiN K antaGonist oraL Anticoagulants for intermEdiate Stroke Risk in Patients With Atrial Fibrillation (SINGLE-AF)

Conditions
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Atrial Fibrillation Patients With Intermediate Stroke Risk

Intervention / Treatment
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* Drug: Anticoagulation group(Apixaban group)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 19 80 years old CHA2DS2-VASc score 1 for male or 2 for female among nonvalvular atrial fibrillation patients Patients who agree to register for this study Patients who can be observed for the progress after treatment Exclusion Criteria: Severe liver or kidney dysfunction Thyroid dysfunction Pregnant or breastfeeding women Malignant tumors that have not been completely cured Severe structural heart disease Predicted survival is less than 12 months Patients who do not understand the content of the study or disagree with it

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anticoagulation group(Apixaban group)<br>Apixaban 5mg twice daily (2.5mg twice daily if meets dose-reduction criteria) for 2 years | Drug: Anticoagulation group(Apixaban group)<br>* Apixaban 5mg twice daily (2.5mg twice daily if meets dose-reduction criteria) for 2 years<br>|
| No Intervention: Nonanticoagulation group<br>Standard treatment except anticoagulant for 2 years | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite outcome | Composite outcome including stroke/systemic embolism, major bleeding, and death | Baseline | 
| Composite outcome | Composite outcome including stroke/systemic embolism, major bleeding, and death | 1 month | 
| Composite outcome | Composite outcome including stroke/systemic embolism, major bleeding, and death | 6 months | 
| Composite outcome | Composite outcome including stroke/systemic embolism, major bleeding, and death | 12 months | 
| Composite outcome | Composite outcome including stroke/systemic embolism, major bleeding, and death | 18 months | 
| Composite outcome | Composite outcome including stroke/systemic embolism, major bleeding, and death | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stroke | )Ischemic stroke specifically refers to central nervous system infarction (brain, spinal cord, or retinal cell death attributable to ischemia) accompanied by overt symptoms, while silent infarction by definition causes no known symptoms. Stroke also broadly includes intracerebral hemorrhage and subarachnoid hemorrhage. | Baseline | 
| Stroke | )Ischemic stroke specifically refers to central nervous system infarction (brain, spinal cord, or retinal cell death attributable to ischemia) accompanied by overt symptoms, while silent infarction by definition causes no known symptoms. Stroke also broadly includes intracerebral hemorrhage and subarachnoid hemorrhage. | 1 month | 
| Stroke | )Ischemic stroke specifically refers to central nervous system infarction (brain, spinal cord, or retinal cell death attributable to ischemia) accompanied by overt symptoms, while silent infarction by definition causes no known symptoms. Stroke also broadly includes intracerebral hemorrhage and subarachnoid hemorrhage. | 6 months | 
| Stroke | )Ischemic stroke specifically refers to central nervous system infarction (brain, spinal cord, or retinal cell death attributable to ischemia) accompanied by overt symptoms, while silent infarction by definition causes no known symptoms. Stroke also broadly includes intracerebral hemorrhage and subarachnoid hemorrhage. | 12 months | 
| Stroke | )Ischemic stroke specifically refers to central nervous system infarction (brain, spinal cord, or retinal cell death attributable to ischemia) accompanied by overt symptoms, while silent infarction by definition causes no known symptoms. Stroke also broadly includes intracerebral hemorrhage and subarachnoid hemorrhage. | 18 months | 
| Stroke | )Ischemic stroke specifically refers to central nervous system infarction (brain, spinal cord, or retinal cell death attributable to ischemia) accompanied by overt symptoms, while silent infarction by definition causes no known symptoms. Stroke also broadly includes intracerebral hemorrhage and subarachnoid hemorrhage. | 24 months | 
| Systemic embolism | Systemic embolism refers to emboli in the arterial circulation, and defined by both clinical and objective evidence of sudden loss of end-organ perfusion. | Baseline | 
| Systemic embolism | Systemic embolism refers to emboli in the arterial circulation, and defined by both clinical and objective evidence of sudden loss of end-organ perfusion. | 1 month | 
| Systemic embolism | Systemic embolism refers to emboli in the arterial circulation, and defined by both clinical and objective evidence of sudden loss of end-organ perfusion. | 6 months | 
| Systemic embolism | Systemic embolism refers to emboli in the arterial circulation, and defined by both clinical and objective evidence of sudden loss of end-organ perfusion. | 12 months | 
| Systemic embolism | Systemic embolism refers to emboli in the arterial circulation, and defined by both clinical and objective evidence of sudden loss of end-organ perfusion. | 18 months | 
| Systemic embolism | Systemic embolism refers to emboli in the arterial circulation, and defined by both clinical and objective evidence of sudden loss of end-organ perfusion. | 24 months | 
| Major bleeding | The International Society on Thrombosis and Haemostasis (ISTH)/Scientific and Standardization Committee (SSC) definitions and bleeding assessment tool are useful for standardizing the reporting of bleeding symptoms. 1. Fatal bleeding. and/or 2. Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome. and/or 3. Bleeding causing a fall in hemoglobin level of 2 g/dL (1.24 mmol/L) or more, or leading to transfusion of two or more units of whole blood or red cells. | Baseline | 
| Major bleeding | The International Society on Thrombosis and Haemostasis (ISTH)/Scientific and Standardization Committee (SSC) definitions and bleeding assessment tool are useful for standardizing the reporting of bleeding symptoms. 1. Fatal bleeding. and/or 2. Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome. and/or 3. Bleeding causing a fall in hemoglobin level of 2 g/dL (1.24 mmol/L) or more, or leading to transfusion of two or more units of whole blood or red cells. | 1 month | 
| Major bleeding | The International Society on Thrombosis and Haemostasis (ISTH)/Scientific and Standardization Committee (SSC) definitions and bleeding assessment tool are useful for standardizing the reporting of bleeding symptoms. 1. Fatal bleeding. and/or 2. Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome. and/or 3. Bleeding causing a fall in hemoglobin level of 2 g/dL (1.24 mmol/L) or more, or leading to transfusion of two or more units of whole blood or red cells. | 6 months | 
| Major bleeding | The International Society on Thrombosis and Haemostasis (ISTH)/Scientific and Standardization Committee (SSC) definitions and bleeding assessment tool are useful for standardizing the reporting of bleeding symptoms. 1. Fatal bleeding. and/or 2. Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome. and/or 3. Bleeding causing a fall in hemoglobin level of 2 g/dL (1.24 mmol/L) or more, or leading to transfusion of two or more units of whole blood or red cells. | 12 months | 
| Major bleeding | The International Society on Thrombosis and Haemostasis (ISTH)/Scientific and Standardization Committee (SSC) definitions and bleeding assessment tool are useful for standardizing the reporting of bleeding symptoms. 1. Fatal bleeding. and/or 2. Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome. and/or 3. Bleeding causing a fall in hemoglobin level of 2 g/dL (1.24 mmol/L) or more, or leading to transfusion of two or more units of whole blood or red cells. | 18 months | 
| Major bleeding | The International Society on Thrombosis and Haemostasis (ISTH)/Scientific and Standardization Committee (SSC) definitions and bleeding assessment tool are useful for standardizing the reporting of bleeding symptoms. 1. Fatal bleeding. and/or 2. Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome. and/or 3. Bleeding causing a fall in hemoglobin level of 2 g/dL (1.24 mmol/L) or more, or leading to transfusion of two or more units of whole blood or red cells. | 24 months | 
| Clinically Relivant Non-Major Bleeding (CRNMB) | 1. Any sign or symptom of hemorrhage (e.g., more bleeding than would be expected for a clinical circumstance, including bleeding found by imaging alone) that does not fit the criteria for the ISTH definition of major bleeding but does meet at least one of the following criteria: i. requiring medical intervention by a healthcare professional ii. leading to hospitalization or increased level of care iii. prompting a face to face (i.e., not just a telephone or electronic communication) evaluation 2. ISTH major bleeding in non-surgical patients is defined as having a symptomatic presentation and 1: i. Fatal bleeding, and/or ii. Bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome, and/or iii. Bleeding causing a fall in hemoglobin level of 20 g L-1 (1.24 mmol L-1) or more, or leading to transfusion of two or more units of whole blood or red cells. | Baseline, 1month, 6 month, 12 month, 18 month, 24 month | 
| Death | the permanent stopping of all the vital bodily activities | Baseline, 1month, 6 month, 12 month, 18 month, 24 month | 
| Transient ischemic attack (TIA) | TIA is brief episodes of neurological dysfunction resulting from focal cerebral ischemia not associated with permanent cerebral infarction. | Baseline, 1month, 6 month, 12 month, 18 month, 24 month | 
| Hospital admission | Hospital admission means admission of a covered person to a hospital as an inpatient for medically necessary and appropriate care and treatment of an Illness or Injury. | Baseline, 1month, 6 month, 12 month, 18 month, 24 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atrial fibrillation, anticoagulation, intermediate stroke risk, efficacy, safety