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

July 2, 2026 updated by: Yonsei University

Atrial fibrillation (AF) increases the risk of stroke, and oral anticoagulation is strongly recommended for patients at high thromboembolic risk. However, for patients with intermediate stroke risk, defined as a CHA₂DS₂-VASc score of 1 in men or 2 in women, randomized evidence supporting anticoagulation remains limited.

The SINGLE-AF trial is an investigator-initiated, multicenter, open-label, adjudicator-masked, superiority randomized trial conducted in South Korea. Eligible patients with AF and intermediate stroke risk are randomly assigned in a 1:1 ratio to receive direct oral anticoagulant (DOAC) therapy or no anticoagulant therapy. Patients assigned to anticoagulation receive a direct oral anticoagulant, primarily apixaban or rivaroxaban. Patients assigned to no anticoagulant therapy do not receive routine oral anticoagulation, although temporary anticoagulation is permitted around rhythm-control procedures when clinically indicated.

The primary objective of this trial is to determine whether DOAC therapy reduces the risk of adverse clinical events compared with no anticoagulant therapy. The primary end point is a composite of stroke, systemic embolism, major bleeding, or cardiovascular death at 24 months after randomization.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1803

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • South Korea
      • Seoul, South Korea
        • Severance Cardiovascular Hospital Yonsei University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

19 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

  1. Patient with atrial fibrillation aged between 19 and 80 years
  2. CHA2DS2-VASc score of 1 (male) or 2 (female)

Exclusion Criteria

  1. Significant liver (aspartate transaminase and/or alanine transaminase > 3 times the upper limit of normal or liver cirrhosis classified as Child-Pugh class B or C) or renal disease (serum creatinine ≥ 3.5 mg/dl or creatinine clearance < 30 ml/min)
  2. Requiring anticoagulation due to surgery with a mechanical prosthetic valve, moderate-to-severe mitral stenosis, or deep vein thrombosis
  3. Significant structural heart disease A. Moderate mitral regurgitation B. Severe valvular regurgitation or stenosis C. Dilated cardiomyopathy D. Hypertrophic cardiomyopathy E. Cardiac amyloidosis
  4. Active malignancy
  5. Pregnancy or breast-feeding
  6. Life expectancy < 1 year
  7. Refuse or unable to understand the written informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
No Intervention: Nonanticoagulation group
Standard treatment except anticoagulant for 2 years
Experimental: Anticoagulation group(DOAC group)
Apixaban 5mg twice daily (2.5mg twice daily if meets dose-reduction criteria) or rivaroxaban 20mg once daily (15mg once daily if meets dose-reduction criteria) for 2 years
Drug: Anticoagulation group(DOAC group)
Apixaban 5mg twice daily (2.5mg twice daily if meets dose-reduction criteria) or rivaroxaban 20mg once daily (15mg once daily if meets dose-reduction criteria) for 2 years

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Composite outcome
Time Frame: 24 months
Composite outcome including stroke/systemic embolism, major bleeding, and cardiovascular death
24 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Stroke
Time Frame: 24 months
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
Major bleeding
Time Frame: 24 months

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
Systemic embolism
Time Frame: 24 months
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
Cardiovascular Death
Time Frame: 24 months
Death due to myocardial infarction, sudden cardiac death, heart failure, stroke, cardiovascular procedures, cardiovascular hemorrhage, and any case of death in which a cardiovascular cause cannot be excluded as adjudicated by a clinical events committee.
24 months
Clinically Relevant Non-Major Bleeding (CRNMB)
Time Frame: 24 months
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.
24 months
Death
Time Frame: 24 months
The permanent stopping of all the vital bodily activities
24 months
Transient ischemic attack (TIA)
Time Frame: 24 months
TIA is brief episodes of neurological dysfunction resulting from focal cerebral ischemia not associated with permanent cerebral infarction.
24 months
Myocardial infarction
Time Frame: 24 months
The definition of myocardial infarction (MI) was based on the Third Universal MI definition
24 months
Hospital admission
Time Frame: 24 months
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.
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Yonsei University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 28, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 21, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 21, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 15, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 15, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 18, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 7, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 2, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 4-2020-0438

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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