Atrial Fibrillation Patients With Intermediate Stroke RiskPhase 4NCT04437654
The Efficacy and Safety of Non-vItamiN K antaGonist oraL Anticoagulants for intermEdiate Stroke Risk in Patients With Atrial Fibrillation (SINGLE-AF)
A Phase 4 study testing Anticoagulation group(DOAC group) in people with Atrial Fibrillation Patients With Intermediate Stroke Risk, run by Yonsei University at 1 site in South Korea.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 19 to 80 years
- Conditions the study is for
- Atrial Fibrillation Patients With Intermediate Stroke Risk
- What is being tested?
- Anticoagulation group(DOAC group)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,803 participants
- Where
- 1 siteSouth Korea
- Study dates
- 28 Jul 2020to 21 Aug 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient with atrial fibrillation aged between 19 and 80 years
- CHA2DS2-VASc score of 1 (male) or 2 (female)
Who cannot join
- 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)
- Requiring anticoagulation due to surgery with a mechanical prosthetic valve, moderate-to-severe mitral stenosis, or deep vein thrombosis
- Significant structural heart disease A. Moderate mitral regurgitation B. Severe valvular regurgitation or stenosis C. Dilated cardiomyopathy D. Hypertrophic cardiomyopathy E. Cardiac amyloidosis
- Active malignancy
- Pregnancy or breast-feeding
- Life expectancy < 1 year
- Refuse or unable to understand the written informed consent
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Severance Cardiovascular Hospital Yonsei University
Seoul
About this study
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.
- Being tested
- Anticoagulation group(DOAC group)
- Keywords
- Atrial fibrillation, anticoagulation, intermediate stroke risk, efficacy, safety
- Medical subject headings
- Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anticoagulation group(DOAC group)Drug
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
| Study group | Role | What they receive |
|---|---|---|
| Anticoagulation group(DOAC group) | Experimental | 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 Receives: Drug: Anticoagulation group(DOAC group) |
| Nonanticoagulation group | No intervention | Standard treatment except anticoagulant for 2 years |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite outcome
Composite outcome including stroke/systemic embolism, major bleeding, and cardiovascular death
Measured: 24 months
Secondary outcomes (9)
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.
Measured: 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.
Measured: 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.
- 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.
Measured: 24 months
Cardiovascular Death
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.
Measured: 24 months
Clinically Relevant Non-Major Bleeding (CRNMB)
- 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.
Measured: 24 months
Death
The permanent stopping of all the vital bodily activities
Measured: 24 months
Transient ischemic attack (TIA)
TIA is brief episodes of neurological dysfunction resulting from focal cerebral ischemia not associated with permanent cerebral infarction.
Measured: 24 months
Myocardial infarction
The definition of myocardial infarction (MI) was based on the Third Universal MI definition
Measured: 24 months
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.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2020
- Study start28 Jul 2020
- Primary completion21 Aug 2025
- Study completion21 Aug 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Atrial Fibrillation Patients With Intermediate Stroke RiskStudies of the same condition, open and under way.
- More trials run by Yonsei UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Taking direct oral anticoagulant (DOAC)
- Masking
- None (open label)
- Enrolment
- 1,803 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yonsei University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04437654
- Sponsor's protocol ID
- 4-2020-0438
- Status last verified
- Jul 2026
- First submitted
- 15 Jun 2020
- Last updated
- 7 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kim D, Lee YS, Shim J, Yu HT, Park J, Park JK, Oh IY, Kang KW, Choi EK, Park KM, Park HS, Kim DH, Park HW, Kim J, Ko JS, Kim D, Kim JY, Kim JB, Sung JH, Kim TH, Uhm JS, Pak HN, Joung B; SINGLE-AF Investigators. Anticoagulation for Atrial Fibrillation with Intermediate Stroke Risk. N Engl J Med. 2026 Aug 28. doi: 10.1056/NEJMoa2607978. Online ahead of print.
PubMed 42663303
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Efficacy and Safety of Non-vItamiN K antaGonist oraL Anticoagulants for intermEdiate Stroke Risk in Patients With Atrial Fibrillation (SINGLE-AF)
- ClinicalTrials.gov ID
- NCT04437654
- Acronym / sponsor ID
- 4-2020-0438
- Keywords
- Atrial fibrillation, anticoagulation, intermediate stroke risk, efficacy, safety
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,803 participants (actual)
- Lead sponsor
- Yonsei UniversityUniversity, hospital or other
- Study start
- 28 Jul 2020 (actual)
- Primary completion
- 21 Aug 2025 (actual)
- Study completion
- 21 Aug 2025 (actual)
- First posted
- 18 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Taking direct oral anticoagulant (DOAC)
| Arm | Type | Receives |
|---|---|---|
| Anticoagulation group(DOAC group) | Experimental | 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 |
| Nonanticoagulation group | No intervention | –Standard treatment except anticoagulant for 2 years |
Who may qualify
- Ages
- 19 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patient with atrial fibrillation aged between 19 and 80 years
- CHA2DS2-VASc score of 1 (male) or 2 (female)
Key exclusion criteria (7 listed)
- 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)
- Requiring anticoagulation due to surgery with a mechanical prosthetic valve, moderate-to-severe mitral stenosis, or deep vein thrombosis
- Significant structural heart disease A. Moderate mitral regurgitation B. Severe valvular regurgitation or stenosis C. Dilated cardiomyopathy D. Hypertrophic cardiomyopathy E. Cardiac amyloidosis
- Active malignancy
- Pregnancy or breast-feeding
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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) |
Primary outcome
Composite outcome
Time frame: 24 months
Composite outcome including stroke/systemic embolism, major bleeding, and cardiovascular death
9 secondary outcomes
Stroke
Time frame: 24 months
Systemic embolism
Time frame: 24 months
Major bleeding
Time frame: 24 months
Cardiovascular Death
Time frame: 24 months
Clinically Relevant Non-Major Bleeding (CRNMB)
Time frame: 24 months
Death
Time frame: 24 months
Transient ischemic attack (TIA)
Time frame: 24 months
Myocardial infarction
Time frame: 24 months
Hospital admission
Time frame: 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2026.
- Derived from this study: PubMed 42663303Kim D, Lee YS, Shim J, Yu HT, Park J, Park JK, Oh IY, Kang KW, Choi EK, Park KM, Park HS, Kim DH, Park HW, Kim J, Ko JS, Kim D, Kim JY, Kim JB, Sung JH, Kim TH, Uhm JS, Pak HN, Joung B; SINGLE-AF Investigators. Anticoagulation for Atrial Fibrillation with Intermediate Stroke Risk. N Engl J Med. 2026 Aug 28. doi: 10.1056/NEJMoa2607978. Online ahead of print.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Anticoagulation group(DOAC group) in people with Atrial Fibrillation Patients With Intermediate Stroke Risk, run by Yonsei University at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite outcome (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04437654, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2026.