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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)

Primary Purpose

Atrial Fibrillation Patients With Intermediate Stroke Risk

Status
Recruiting
Phase
Phase 4
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Anticoagulation group(Apixaban group)
Sponsored by
Yonsei University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Atrial Fibrillation Patients With Intermediate Stroke Risk focused on measuring Atrial fibrillation, anticoagulation, intermediate stroke risk, efficacy, safety

Eligibility Criteria

19 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Severance Cardiovascular Hospital Yonsei UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Anticoagulation group(Apixaban group)

Nonanticoagulation group

Arm Description

Apixaban 5mg twice daily (2.5mg twice daily if meets dose-reduction criteria) for 2 years

Standard treatment except anticoagulant for 2 years

Outcomes

Primary Outcome Measures

Composite outcome
Composite outcome including stroke/systemic embolism, major bleeding, and death
Composite outcome
Composite outcome including stroke/systemic embolism, major bleeding, and death
Composite outcome
Composite outcome including stroke/systemic embolism, major bleeding, and death
Composite outcome
Composite outcome including stroke/systemic embolism, major bleeding, and death
Composite outcome
Composite outcome including stroke/systemic embolism, major bleeding, and death
Composite outcome
Composite outcome including stroke/systemic embolism, major bleeding, and death

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Death
the permanent stopping of all the vital bodily activities
Transient ischemic attack (TIA)
TIA is brief episodes of neurological dysfunction resulting from focal cerebral ischemia not associated with permanent cerebral infarction.
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.

Full Information

First Posted
June 15, 2020
Last Updated
January 30, 2023
Sponsor
Yonsei University
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1. Study Identification

Unique Protocol Identification Number
NCT04437654
Brief Title
The Efficacy and Safety of Non-vItamiN K antaGonist oraL Anticoagulants for intermEdiate Stroke Risk in Patients With Atrial Fibrillation (SINGLE-AF)
Official Title
The Efficacy and Safety of Non-vItamiN K antaGonist oraL Anticoagulants for intermEdiate Stroke Risk in Patients With Atrial Fibrillation (SINGLE-AF)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 28, 2020 (Actual)
Primary Completion Date
July 2026 (Anticipated)
Study Completion Date
October 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yonsei University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atrial Fibrillation Patients With Intermediate Stroke Risk
Keywords
Atrial fibrillation, anticoagulation, intermediate stroke risk, efficacy, safety

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1800 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Anticoagulation group(Apixaban group)
Arm Type
Experimental
Arm Description
Apixaban 5mg twice daily (2.5mg twice daily if meets dose-reduction criteria) for 2 years
Arm Title
Nonanticoagulation group
Arm Type
No Intervention
Arm Description
Standard treatment except anticoagulant for 2 years
Intervention Type
Drug
Intervention Name(s)
Anticoagulation group(Apixaban group)
Intervention Description
Apixaban 5mg twice daily (2.5mg twice daily if meets dose-reduction criteria) for 2 years
Primary Outcome Measure Information:
Title
Composite outcome
Description
Composite outcome including stroke/systemic embolism, major bleeding, and death
Time Frame
Baseline
Title
Composite outcome
Description
Composite outcome including stroke/systemic embolism, major bleeding, and death
Time Frame
1 month
Title
Composite outcome
Description
Composite outcome including stroke/systemic embolism, major bleeding, and death
Time Frame
6 months
Title
Composite outcome
Description
Composite outcome including stroke/systemic embolism, major bleeding, and death
Time Frame
12 months
Title
Composite outcome
Description
Composite outcome including stroke/systemic embolism, major bleeding, and death
Time Frame
18 months
Title
Composite outcome
Description
Composite outcome including stroke/systemic embolism, major bleeding, and death
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Stroke
Description
)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.
Time Frame
Baseline
Title
Stroke
Description
)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.
Time Frame
1 month
Title
Stroke
Description
)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.
Time Frame
6 months
Title
Stroke
Description
)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.
Time Frame
12 months
Title
Stroke
Description
)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.
Time Frame
18 months
Title
Stroke
Description
)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.
Time Frame
24 months
Title
Systemic embolism
Description
Systemic embolism refers to emboli in the arterial circulation, and defined by both clinical and objective evidence of sudden loss of end-organ perfusion.
Time Frame
Baseline
Title
Systemic embolism
Description
Systemic embolism refers to emboli in the arterial circulation, and defined by both clinical and objective evidence of sudden loss of end-organ perfusion.
Time Frame
1 month
Title
Systemic embolism
Description
Systemic embolism refers to emboli in the arterial circulation, and defined by both clinical and objective evidence of sudden loss of end-organ perfusion.
Time Frame
6 months
Title
Systemic embolism
Description
Systemic embolism refers to emboli in the arterial circulation, and defined by both clinical and objective evidence of sudden loss of end-organ perfusion.
Time Frame
12 months
Title
Systemic embolism
Description
Systemic embolism refers to emboli in the arterial circulation, and defined by both clinical and objective evidence of sudden loss of end-organ perfusion.
Time Frame
18 months
Title
Systemic embolism
Description
Systemic embolism refers to emboli in the arterial circulation, and defined by both clinical and objective evidence of sudden loss of end-organ perfusion.
Time Frame
24 months
Title
Major bleeding
Description
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.
Time Frame
Baseline
Title
Major bleeding
Description
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.
Time Frame
1 month
Title
Major bleeding
Description
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.
Time Frame
6 months
Title
Major bleeding
Description
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.
Time Frame
12 months
Title
Major bleeding
Description
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.
Time Frame
18 months
Title
Major bleeding
Description
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.
Time Frame
24 months
Title
Clinically Relivant Non-Major Bleeding (CRNMB)
Description
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.
Time Frame
Baseline, 1month, 6 month, 12 month, 18 month, 24 month
Title
Death
Description
the permanent stopping of all the vital bodily activities
Time Frame
Baseline, 1month, 6 month, 12 month, 18 month, 24 month
Title
Transient ischemic attack (TIA)
Description
TIA is brief episodes of neurological dysfunction resulting from focal cerebral ischemia not associated with permanent cerebral infarction.
Time Frame
Baseline, 1month, 6 month, 12 month, 18 month, 24 month
Title
Hospital admission
Description
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.
Time Frame
Baseline, 1month, 6 month, 12 month, 18 month, 24 month

10. Eligibility

Sex
All
Gender Based
Yes
Gender Eligibility Description
CHA2DS2-VASc score 1 for male, 2 for female.
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Boyoung Joung
Phone
82-2-2228-8447
Email
cby6908@yuhs.ac
Facility Information:
Facility Name
Severance Cardiovascular Hospital Yonsei University
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Boyoung Joung
Phone
82-2-2228-8447
Email
cby6908@yuhs.ac

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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