The Rhythm Evaluation for AntiCoagulaTion With Continuous Monitoring of Atrial Fibrillation

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified March 2026 by Johns Hopkins University
Sponsor
Johns Hopkins University
Information Provided by (Responsible Party)
Johns Hopkins University
Clinicaltrials.gov Identifier
NCT05836987
Other Study ID Numbers:
IRB00354588
First Submitted
April 18, 2023
First Posted
April 30, 2023
Last Update Posted
April 8, 2026
Last Verified
March 2026

ClinicalTrials.gov processed this data on April 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

REACT-AF is a prospective, unblinded, randomized (1:1 allocation), multi-center, investigational clinical trial of men and women aged 22-85 with a documented history of symptomatic or asymptomatic paroxysmal or persistent (AF) and a moderate risk of stroke measured by CHA2DS2-VASc score 1-4 for men, 2-4 for women (which stands for Congestive heart failure, Hypertension, Age ≥75 (doubled), Diabetes, Stroke (doubled), Vascular disease, age 65 to 74 and sex category (female)). Participants randomized to the experimental arm (on demand DOAC) will take the participants DOAC for 30 consecutive days following a qualifying AF episode (i.e., greater than1 hour) detected by the AFSW. Participants randomized to the standard of care (control) arm will remain on previously prescribed continuous DOAC throughout the study.

A total of 5350 participants will be enrolled across up to 100 study sites targeting two-thirds academic and one-third private practices, with academic practices also enrolling from affiliated community sites. The investigators anticipate evaluating 7643 consented individuals with external monitoring to ensure that a low AF burden population will be randomized. Up to 200 participants may be enrolled at any one site, and participation will last up to 60 months.

Condition or DiseaseIntervention/Treatment
Atrial Fibrillation
Device: AFSW Guided DOACDrug: Continuous DOAC therapy

Study Design

Study TypeInterventional
Actual Enrollment5350 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingSingle
Primary PurposePrevention
Official TitleREACT-AF: Rhythm Evaluation for AntiCoagulaTion With Continuous Monitoring of Atrial Fibrillation
Study Start DateJuly 12, 2023
Actual Primary Completion Date3yrs 2mos from now
Actual Study Completion Date3yrs 2mos from now

Groups and Cohorts

Group/CohortIntervention/Treatment
AFSW Guided DOAC
All participants randomized to the experimental arm will be provided with an AFSW that will be linked to the participants Apple watch and the secure REACT-AF app within the Eureka cloud. The AFSW will intermittently and passively assess for rhythm irregularities consistent with AF and notify the wearer and coordinating center if a threshold AF event has occurred.
Device: AFSW Guided DOAC
The AFSW will intermittently and passively assess for rhythm irregularities consistent with AF and notify the wearer and coordinating center if a threshold AF event has occurred.
Continuous DOAC therapy
All participants randomized to the control arm will remain on previously prescribed FDA-approved DOAC regimen as indicated by current practice standards. These participants will continuously take DOAC through the course of the study as prescribed by the participants primary physician unless otherwise contraindicated. Participants in the control arm will also use the REACT-AF mobile app within the Eureka platform via Apple watch for study follow-up activities, but the participants will not receive an AFSW and any personally owned Apple Watch will not be loaded with the customized REACT-AF detection algorithm nor participant notification apps.
Drug: Continuous DOAC therapy
DOACs will be prescribed to patients according to the treating healthcare provider(s) according to labeling instructions.

Outcome Measures

Primary Outcome Measures
  1. To assess whether AFSW-guided, time-delimited DOAC therapy is non-inferior to continuous DOAC therapy for a composite endpoint that includes: (1) Ischemic stroke; (2) Systemic embolism; (3) All-cause mortality.
    The primary objective (efficacy objective) of the REACT-AF trial is to assess whether AFSW-guided, time-delimited DOAC therapy is non-inferior to continuous DOAC therapy for a composite endpoint that includes: (1) Ischemic stroke; (2) Systemic embolism; and (3) All-cause mortality. Stroke is defined as an acute episode of focal or global neurological dysfunction caused by brain, spinal cord, or retinal vascular injury as a result of hemorrhage or infarction; and classified as ischemic, hemorrhagic, or cause unknown based on CT or Magnetic Resonance (MR) scanning or autopsy. Systemic embolism is defined as an acute vascular occlusion of the extremities or any organ and must be documented by angiography, surgery, scintigraphy, or autopsy and require hospitalization. All-cause mortality will be defined as the underlying disease or injury that initiates the train of events resulting in death.
Secondary Outcome Measures
  1. To assess whether AFSW-guided, time-delimited DOAC therapy significantly reduces major bleeding events compared to continuous DOAC therapy.
    Oral anticoagulation carries a risk of major bleeding, including life-threatening hemorrhage, the intervention is expected to reduce the safety endpoint, major bleeding, by \> 35%, and the study is powered for the superiority of the safety endpoint. Major bleeding will be defined as requiring hospitalization and by ≥1 of the following International Society on Thrombosis and Haemostasis (ISTH) criteria: (1) Bleeding associated with a reduction in hemoglobin level of at least 2.0 g/dL; (2) Bleeding leading to transfusion of at least two units of blood or packed cells; or (3) Symptomatic bleeding in a critical area or organ such as intraocular, intracranial, intraspinal or intramuscular with compartment syndrome, retroperitoneal bleeding, intra-articular bleeding, or pericardial bleeding.

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
1. 22-85 years of age. 2. English speaking participants. Spanish-only speakers may be included in the future at select sites appropriately translated. 3. History of non-permanent atrial fibrillation. 4. CHA2DS2-VASC score of 1-4 for men and 2-4 for women without prior stroke or Transient Ischemic Attack (TIA), The CHA2DS2-VASc score is a point-based system used to stratify the risk of stroke in Atrial Fibrillation (AF) patients. The acronym CHA2DS2-VASc stands for congestive heart failure, hypertension, age ≥75 (doubled), diabetes, stroke (doubled), vascular disease, age 65 to 74 and sex category (female). Congestive heart failure defined as: The presence of signs and symptoms of either right (elevated central venous pressure, hepatomegaly, dependent edema) or left ventricular failure (exertional dyspnea, cough, fatigue, orthopnea, paroxysmal nocturnal dyspnea, cardiac enlargement, rales, gallop rhythm, pulmonary venous congestion) or both, confirmed by non-invasive or invasive measurements demonstrating objective evidence of cardiac dysfunction and/or ejection fraction \< 40%. 5. The participant is on a DOAC at the time of screening and willing to stay on DOAC for duration of study. 6. Willing and able to comply with the protocol, including:
Possession of a smart watch-compatible smart phone (iPhone that supports the latest shipping iOS) with a cellular service plan
Be willing to wear the smart watch for the suggested minimum of 14 hours a day
Expected to be within cellular service range at least 80% of the time 7. Willing and able to discontinue DOAC 8. The participant is willing and able to provide informed consent.
Exclusion Criteria
1. Valvular or permanent atrial fibrillation. 2. Current treatment with warfarin and unwilling or unable to take a DOAC. 3. The participant is a woman who is pregnant or nursing. 4. The participant is being treated with chronic aspirin, another anti-platelet agent, or chronic NSAIDS outside of current medical guidelines (e.g., primary stroke prevention in patients with atrial fibrillation, primary prevention of cardiovascular events, pain relief, fever, gout) and is unwilling or unable to discontinue use for the study duration. 5. Existing cardiac rhythm device or indication for a permanent pacemaker, Implantable Cardioverter-Defibrillator (ICD) or Cardiac Resynchronization Therapy (CRT) device or planned insertable cardiac monitor. Insertable cardiac monitors are permitted unless they are being used to guide anticoagulation treatment. 6. Known or suspected symptomatic or asymptomatic atrial fibrillation lasting ≥ 1 hour/month over the last 3 months. 7. Any documented single AF episode lasting ≥ 1 hour on standard of care or study-provided external cardiac monitor of \> 6 days duration performed within 45 days prior to randomization. Shorter monitoring durations may be acceptable for inclusion at the discretion of the site PI based on the totality of monitoring data and approval of the study PI. 8. Ablation for AF within the last 2 months. 9. Prior or anticipated left atrial appendage occlusion or ligation. 10. Mechanical prosthetic valve(s) or severe valve disease. 11. Hypertrophic cardiomyopathy. 12. Participant needs DOAC for reasons other than preventing stroke or arterial embolism resulting from AF (i.e., preventing Deep Vein Thrombosis (DVT) or PE) or needs permanent OAC (i.e., congenital heart defects, prosthetic heart valve). 13. Participants deemed high risk for non-cardioembolic stroke (i.e., significant carotid artery disease defined as stenosis \> 75%) based on the investigator's discretion. 14. The participant is enrolled, has participated within the last 30 days, or is planning to participate in a concurrent drug and/or device study during the course of this clinical trial. Co-enrollment in concurrent trials is only allowed with documented pre-approval from the study manager; there is no concern that co-enrollment could confound the results of this trial. 15. The participant has a tattoo, birthmark, or surgical scar over the dorsal wrist area on the ipsilateral side that the AFSW may be worn. 16. The participant has a tremor on their ipsilateral side that the AFSW may be worn. 17. Any concomitant condition that, in the investigator's opinion, would not allow safe participation in the study (e.g., drug addiction, alcohol abuse). 18. Known hypersensitivity or contraindication to direct oral anticoagulants. 19. Documented prior stroke (ischemic or hemorrhagic) or transient ischemic attack. 20. Reversible causes of AF (e.g., cardiac surgery, pulmonary embolism, untreated hyperthyroidism). AF ablation does not constitute reversible AF. 21. \> 5% burden of premature atrial or ventricular depolarizations on pre-enrollment cardiac monitoring. 22. History of atrial flutter that has not been treated with ablation (participants in atrial flutter and have been ablated are eligible for enrollment). 23. Stage 4 or 5 chronic kidney disease. 24. Conditions associated with an increased risk of bleeding:
Major surgery in the previous month
Planned surgery or intervention in the next three months that would require cessation of anticoagulation \> 2 weeks.
History of intracranial, intraocular, spinal, retroperitoneal, or atraumatic intra- articular bleeding
Gastrointestinal hemorrhage within the past year unless the cause has been permanently eliminated (e.g., by surgery)
Symptomatic or endoscopically documented gastroduodenal ulcer disease in the previous 30 days
Hemorrhagic disorder or bleeding diathesis
Need for anticoagulant treatment for disorders other than AF
Uncontrolled hypertension (Systolic Blood Pressure \>180 mmHg and/or Diastolic Blood Pressure \>100 mmHg)

Contacts and Locations

Sponsors and CollaboratorsJohns Hopkins University
Locations
Banner University | Phoenix Arizona, United States, 85006University of Southern California - Keck School of Medicine | Los Angeles California, United States, 90033University of California Los Angeles (UCLA Health) | Los Angeles California, United States, 90095UC Davis Health | Sacramento California, United States, 95817Scripps Health | San Diego California, United States, 92103Kaiser Permanente | San Francisco California, United States, 94115Stanford University | Stanford California, United States, 94305University of Colorado | Aurora Colorado, United States, 80045South Denver Cardiology Associates, P.C. | Littleton Colorado, United States, 80120St. Elizabeth's Medical Center | Washington D.C. District of Columbia, United States, 20032Medical Faculty Associates George Washington University | Washington D.C. District of Columbia, United States, 20037BayCare Health Systems | Clearwater Florida, United States, 33759University of Florida | Gainesville Florida, United States, 32611Mayo Clinic | Jacksonville Florida, United States, 32224University of Miami - Leonard S. Miller SOM | Miami Florida, United States, 33136Sarasota Memorial Health Care System | Sarasota Florida, United States, 34236Cleveland Clinic Florida | Stuart Florida, United States, 34994Baycare Health Systems Clearwater | Winter Haven Florida, United States, 33881Emory University | Atlanta Georgia, United States, 30332Georgia Arrhythmia Consultants and Research Institute | Warner Robins Georgia, United States, 31093University of Illinois Chicago | Chicago Illinois, United States, 60607Northwestern University | Chicago Illinois, United States, 60611Rush University Medical Center | Chicago Illinois, United States, 60612University of Chicago | Chicago Illinois, United States, 60637Loyola University Chicago | Chicago Illinois, United States, 60660Alexian Brothers Health System | Elk Grove Village Illinois, United States, 60007NorthShore University HealthSystem | Evanston Illinois, United States, 60201Midwest Cardiovascular Institute | Naperville Illinois, United States, 60540Ascension St. Vincent | Indianapolis Indiana, United States, 46260University of Iowa Hospitals and Clinics | Iowa City Iowa, United States, 52242Maine Medical Partners MaineHealth Cardiology | Scarborough Maine, United States, 04074Johns Hopkins Univeristy | Baltimore Maryland, United States, 21218Tufts Medical Center | Boston Massachusetts, United States, 02111Mass General Hospital | Boston Massachusetts, United States, 02114Brigham and Women's Hospital | Boston Massachusetts, United States, 02115Boston Medical Center | Boston Massachusetts, United States, 02118BMC - Brighton | Boston Massachusetts, United States, 02135Beth Israel Deaconess Medical Center | Boston Massachusetts, United States, 02215Lahey Hospital & Medical Center | Burlington Massachusetts, United States, 01805UMass Chan Medical School | Worcester Massachusetts, United States, 01655Henry Ford Health | Detroit Michigan, United States, 48202Corewell Health (Former Spectrum Health) | Grand Rapids Michigan, United States, 49503Trinity Health Grand Rapids/Mercy Health | Grand Rapids Michigan, United States, 49503William Beaumont Hospital | Royal Oak Michigan, United States, 48073Trinity Health Michigan Heart - Ann Arbor | Ypsilanti Michigan, United States, 48197Essentia Health The Duluth Clinic | Duluth Minnesota, United States, 55812Minneapolis Heart Institute Foundation | Minneapolis Minnesota, United States, 55407Hennepin Healthcare Research Institute | Minneapolis Minnesota, United States, 55415University of Minnesota | Minneapolis Minnesota, United States, 55455University Health Truman Medical Center | Kansas City Missouri, United States, 64108Washington University School of Medicine | St Louis Missouri, United States, 63110Advanced Heart and Vascular Institute of Hunterdon | Flemington New Jersey, United States, 08822Hackensack Meridian Health | Hackensack New Jersey, United States, 07601Rutgers, the State University of New Jersey | Piscataway New Jersey, United States, 08854The Valley Hospital, Inc. | Ridgewood New Jersey, United States, 07450University of New Mexico Health Sciences Center | Albuquerque New Mexico, United States, 87102Presbyterian Healthcare Services | Albuquerque New Mexico, United States, 87106University at Buffalo | Buffalo New York, United States, 14214NYU Langone Health | New York New York, United States, 10016Columbia University Medical Center | New York New York, United States, 10032Weill Medical College of Cornell University | New York New York, United States, 10065NewYork Presbyterian - Queens | Queens New York, United States, 11355Staten Island University Hospital-Northwell Health | Staten Island New York, United States, 10305Stony Brook University | Stony Brook New York, United States, 11794Westchester Medical Center | Valhalla New York, United States, 10595White Plains Hospital | White Plains New York, United States, 10601University of North Carolina | Chapel Hill North Carolina, United States, 27599Wake Forest Baptist Health | Winston-Salem North Carolina, United States, 27157The Lindner Center for Research and Education at The Christ Hospital | Cincinnati Ohio, United States, 45219University of Cincinnati College of Medicine | Cincinnati Ohio, United States, 45267Ohio State University Medical Center | Columbus Ohio, United States, 43210OhioHealth Research Institute | Columbus Ohio, United States, 43214Wooster Community Hospital | Wooster Ohio, United States, 44691University of Oklahoma Health Sciences Center | Oklahoma City Oklahoma, United States, 73104Cardiology Consultants of Philadelphia | Paoli Pennsylvania, United States, 19301Thomas Jefferson University | Philadelphia Pennsylvania, United States, 19144Allegheny Singer Research Institute | Pittsburgh Pennsylvania, United States, 15212Penn State Health Medical Group Berks Cardiology | Wyomissing Pennsylvania, United States, 19610Rhode Island Hospital | Providence Rhode Island, United States, 02903Medical University of South Carolina | Charleston South Carolina, United States, 29425MUSC Health Heart and Vascular | Columbia South Carolina, United States, 29204Texas Cardiac Arrhythmia Research Foundation | Austin Texas, United States, 78705University of Texas Southwestern Medical Center | Dallas Texas, United States, 75390Baylor College of Medicine | Houston Texas, United States, 77030Houston Methodist Hospital | Houston Texas, United States, 77030University of Texas Health Science Center at Houston | Houston Texas, United States, 77030University of Utah | Salt Lake City Utah, United States, 84112University of Virginia | Charlottesville Virginia, United States, 22903James River Cardiology | Richmond Virginia, United States, 23229Virginia Commonwealth University | Richmond Virginia, United States, 23284St. Joseph Medical Center Tacoma | Tacoma Washington, United States, 98405University of Wisconsin | Madison Wisconsin, United States, 53706Medical College of Wisconsin Froedtert Hospital | Milwaukee Wisconsin, United States, 53226
Investigators
Principal Investigator: Rod Passman, Northwestern UniversityPrincipal Investigator: Dan Hanley, Johns Hopkins University