The Rhythm Evaluation for AntiCoagulaTion With Continuous Monitoring of Atrial Fibrillation
- Conditions
- Atrial Fibrillation
- Interventions
- Device: AFSW Guided DOACDrug: Continuous DOAC therapy
- Registration Number
- NCT05836987
- Lead Sponsor
- Johns Hopkins University
- Brief Summary
REACT-AF is a multicenter prospective, randomized, open-label, blinded endpoint (PROBE design), controlled trial comparing the current Standard Of Care (SOC) of continuous Direct Oral Anticoagulation (DOAC) use versus time-delimited (1 month) DOAC guided by an AF-sensing Smart Watch (AFSW) in participants with a history of paroxysmal or persistent Atrial Fibrillation (AF) and low-to-moderate stroke risk.
- Detailed 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 5350
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22-85 years of age.
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English speaking participants. Spanish-only speakers may be included in the future at select sites appropriately translated.
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History of non-permanent atrial fibrillation.
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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%.
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The participant is on a DOAC at the time of screening and willing to stay on DOAC for duration of study.
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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
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Willing and able to discontinue DOAC
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The participant is willing and able to provide informed consent.
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Valvular or permanent atrial fibrillation.
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Current treatment with warfarin and unwilling or unable to take a DOAC.
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The participant is a woman who is pregnant or nursing.
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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.
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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.
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Known or suspected symptomatic or asymptomatic atrial fibrillation lasting ≥ 1 hour/month over the last 3 months.
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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.
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Ablation for AF within the last 2 months.
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Prior or anticipated left atrial appendage occlusion or ligation.
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Mechanical prosthetic valve(s) or severe valve disease.
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Hypertrophic cardiomyopathy.
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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).
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Participants deemed high risk for non-cardioembolic stroke (i.e., significant carotid artery disease defined as stenosis > 75%) based on the investigator's discretion.
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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.
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The participant has a tattoo, birthmark, or surgical scar over the dorsal wrist area on the ipsilateral side that the AFSW may be worn.
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The participant has a tremor on their ipsilateral side that the AFSW may be worn.
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Any concomitant condition that, in the investigator's opinion, would not allow safe participation in the study (e.g., drug addiction, alcohol abuse).
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Known hypersensitivity or contraindication to direct oral anticoagulants.
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Documented prior stroke (ischemic or hemorrhagic) or transient ischemic attack.
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Reversible causes of AF (e.g., cardiac surgery, pulmonary embolism, untreated hyperthyroidism). AF ablation does not constitute reversible AF.
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> 5% burden of premature atrial or ventricular depolarizations on pre-enrollment cardiac monitoring.
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History of atrial flutter that has not been treated with ablation (participants in atrial flutter and have been ablated are eligible for enrollment).
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Stage 4 or 5 chronic kidney disease.
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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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description AFSW Guided DOAC 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. Continuous DOAC therapy 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.
- Primary Outcome Measures
Name Time Method 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. At 60 months 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
Name Time Method To assess whether AFSW-guided, time-delimited DOAC therapy significantly reduces major bleeding events compared to continuous DOAC therapy. At 60 months 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.
Trial Locations
- Locations (84)
Banner University
🇺🇸Phoenix, Arizona, United States
University of Southern California - Keck School of Medicine
🇺🇸Los Angeles, California, United States
Stanford University
🇺🇸Stanford, California, United States
Medical Faculty Associates George Washington University
🇺🇸Washington, District of Columbia, United States
University of California Los Angeles (UCLA Health)
🇺🇸Los Angeles, California, United States
St. Elizabeth's Medical Center
🇺🇸Washington, District of Columbia, United States
University of Florida
🇺🇸Gainesville, Florida, United States
UC Davis Health
🇺🇸Sacramento, California, United States
Scripps Health
🇺🇸San Diego, California, United States
University of Colorado
🇺🇸Aurora, Colorado, United States
South Denver Cardiology Associates, P.C.
🇺🇸Littleton, Colorado, United States
BayCare Health Systems
🇺🇸Clearwater, Florida, United States
Mayo Clinic
🇺🇸Jacksonville, Florida, United States
University of Miami - Leonard S. Miller SOM
🇺🇸Miami, Florida, United States
Sarasota Memorial Health Care System
🇺🇸Sarasota, Florida, United States
Cleveland Clinic Florida
🇺🇸Stuart, Florida, United States
Baycare Health Systems Clearwater
🇺🇸Winter Haven, Florida, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Georgia Arrhythmia Consultants and Research Institute
🇺🇸Warner Robins, Georgia, United States
University of Illinois Chicago
🇺🇸Chicago, Illinois, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Loyola University Chicago
🇺🇸Chicago, Illinois, United States
Alexian Brothers Health System
🇺🇸Elk Grove Village, Illinois, United States
NorthShore University HealthSystem
🇺🇸Evanston, Illinois, United States
Midwest Cardiovascular Institute
🇺🇸Naperville, Illinois, United States
Ascension St. Vincent
🇺🇸Indianapolis, Indiana, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
Maine Medical Partners MaineHealth Cardiology
🇺🇸Scarborough, Maine, United States
Johns Hopkins Univeristy
🇺🇸Baltimore, Maryland, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Boston Medical Center
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Lahey Hospital & Medical Center
🇺🇸Burlington, Massachusetts, United States
UMass Chan Medical School
🇺🇸Worcester, Massachusetts, United States
Henry Ford Health
🇺🇸Detroit, Michigan, United States
Corewell Health (Former Spectrum Health)
🇺🇸Grand Rapids, Michigan, United States
Trinity Health Grand Rapids/Mercy Health
🇺🇸Grand Rapids, Michigan, United States
William Beaumont Hospital
🇺🇸Royal Oak, Michigan, United States
Trinity Health Michigan Heart - Ann Arbor
🇺🇸Ypsilanti, Michigan, United States
Essentia Health The Duluth Clinic
🇺🇸Duluth, Minnesota, United States
Hennepin Healthcare Research Institute
🇺🇸Minneapolis, Minnesota, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
University Health Truman Medical Center
🇺🇸Kansas City, Missouri, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Hackensack Meridian Health
🇺🇸Hackensack, New Jersey, United States
Rutgers, the State University of New Jersey
🇺🇸Piscataway, New Jersey, United States
The Valley Hospital, Inc.
🇺🇸Ridgewood, New Jersey, United States
University of New Mexico Health Sciences Center
🇺🇸Albuquerque, New Mexico, United States
Presbyterian Healthcare Services
🇺🇸Albuquerque, New Mexico, United States
University at Buffalo
🇺🇸Buffalo, New York, United States
NYU Langone Health
🇺🇸New York, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
NewYork Presbyterian - Queens
🇺🇸Queens, New York, United States
Weill Medical College of Cornell University
🇺🇸New York, New York, United States
Staten Island University Hospital-Northwell Health
🇺🇸Staten Island, New York, United States
Stony Brook University
🇺🇸Stony Brook, New York, United States
White Plains Hospital
🇺🇸White Plains, New York, United States
Wooster Community Hospital
🇺🇸Wooster, Ohio, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Westchester Medical Center
🇺🇸Valhalla, New York, United States
University of North Carolina
🇺🇸Chapel Hill, North Carolina, United States
Wake Forest Baptist Health
🇺🇸Winston-Salem, North Carolina, United States
The Lindner Center for Research and Education at The Christ Hospital
🇺🇸Cincinnati, Ohio, United States
University of Cincinnati College of Medicine
🇺🇸Cincinnati, Ohio, United States
Ohio State University Medical Center
🇺🇸Columbus, Ohio, United States
Penn State Health Medical Group Berks Cardiology
🇺🇸Wyomissing, Pennsylvania, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States
Allegheny Singer Research Institute
🇺🇸Pittsburgh, Pennsylvania, United States
MUSC Health Heart and Vascular
🇺🇸Columbia, South Carolina, United States
Texas Cardiac Arrhythmia Research Foundation
🇺🇸Austin, Texas, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Houston Methodist Hospital
🇺🇸Houston, Texas, United States
University of Texas Health Science Center at Houston
🇺🇸Houston, Texas, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
St. Joseph Medical Center Tacoma
🇺🇸Tacoma, Washington, United States
University of Wisconsin
🇺🇸Madison, Wisconsin, United States
Medical College of Wisconsin Froedtert Hospital
🇺🇸Milwaukee, Wisconsin, United States