The Rhythm Evaluation for AntiCoagulaTion With Continuous Monitoring of Atrial Fibrillation
Purpose
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.
Condition
- Atrial Fibrillation
Eligibility
- Eligible Ages
- Between 22 Years and 85 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- 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
- 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)
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- Participants randomized (1:1) to the experimental arm (AFSW-guided DOAC) will only take DOAC for 30 consecutive days following a qualifying AF episode (i.e., greater than 1 hour) detected by the participants AFSW if no further AF is detected. Participants randomized to the standard of care arm will remain on continuous DOAC throughout the study.
- Primary Purpose
- Prevention
- Masking
- Single (Outcomes Assessor)
- Masking Description
- Adjudication of safety events will be performed by a Clinical Endpoint Committee made up of blinded assessors. The Data Coordinating Center (DCC) blinded statistician(s) will also be blinded.
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental 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. |
|
|
Active Comparator 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. |
|
Recruiting Locations
University of Southern California - Keck School of Medicine
Los Angeles, California 90033
Los Angeles, California 90033
University of California Los Angeles (UCLA Health)
Los Angeles, California 90095
Los Angeles, California 90095
Scripps Health
San Diego, California 92103
San Diego, California 92103
Stanford University
Stanford, California 94305
Stanford, California 94305
University of Colorado
Aurora, Colorado 80045
Aurora, Colorado 80045
South Denver Cardiology Associates, P.C.
Littleton, Colorado 80120
Littleton, Colorado 80120
St. Elizabeth's Medical Center
Washington, District of Columbia 20032
Washington, District of Columbia 20032
Medical Faculty Associates George Washington University
Washington, District of Columbia 20037
Washington, District of Columbia 20037
BayCare Health Systems
Clearwater, Florida 33759
Clearwater, Florida 33759
Mayo Clinic
Jacksonville, Florida 32224
Jacksonville, Florida 32224
University of Miami - Leonard S. Miller SOM
Miami, Florida 33136
Miami, Florida 33136
Sarasota Memorial Health Care System
Sarasota, Florida 34236
Sarasota, Florida 34236
Baycare Health Systems Clearwater
Winter Haven, Florida 33881
Winter Haven, Florida 33881
Georgia Arrhythmia Consultants and Research Institute
Warner Robins, Georgia 31093
Warner Robins, Georgia 31093
Northwestern University
Chicago, Illinois 60611
Chicago, Illinois 60611
Rush University Medical Center
Chicago, Illinois 60612
Chicago, Illinois 60612
University of Chicago
Chicago, Illinois 60637
Chicago, Illinois 60637
Loyola University Chicago
Chicago, Illinois 60660
Chicago, Illinois 60660
Alexian Brothers Health System
Elk Grove Village, Illinois 60007
Elk Grove Village, Illinois 60007
NorthShore University HealthSystem
Evanston, Illinois 60201
Evanston, Illinois 60201
Midwest Cardiovascular Institute
Naperville, Illinois 60540
Naperville, Illinois 60540
Ascension St. Vincent
Indianapolis, Indiana 46260
Indianapolis, Indiana 46260
University of Iowa Hospitals and Clinics
Iowa City, Iowa 52242
Iowa City, Iowa 52242
Maine Medical Partners MaineHealth Cardiology
Scarborough, Maine 04074
Scarborough, Maine 04074
Johns Hopkins Univeristy
Baltimore, Maryland 21218
Baltimore, Maryland 21218
Tufts Medical Center
Boston, Massachusetts 02111
Boston, Massachusetts 02111
Brigham and Women's Hospital
Boston, Massachusetts 02115
Boston, Massachusetts 02115
Boston Medical Center
Boston, Massachusetts 02118
Boston, Massachusetts 02118
Beth Israel Deaconess Medical Center
Boston, Massachusetts 02215
Boston, Massachusetts 02215
Lahey Hospital & Medical Center
Burlington, Massachusetts 01805
Burlington, Massachusetts 01805
UMass Chan Medical School
Worcester, Massachusetts 01655
Worcester, Massachusetts 01655
Corewell Health (Former Spectrum Health)
Grand Rapids, Michigan 49503
Grand Rapids, Michigan 49503
Trinity Health Grand Rapids/Mercy Health
Grand Rapids, Michigan 49503
Grand Rapids, Michigan 49503
William Beaumont Hospital
Royal Oak, Michigan 48073
Royal Oak, Michigan 48073
Trinity Health Michigan Heart - Ann Arbor
Ypsilanti, Michigan 48197
Ypsilanti, Michigan 48197
Essentia Health The Duluth Clinic
Duluth, Minnesota 55812
Duluth, Minnesota 55812
Hennepin Healthcare Research Institute
Minneapolis, Minnesota 55415
Minneapolis, Minnesota 55415
University of Minnesota
Minneapolis, Minnesota 55455
Minneapolis, Minnesota 55455
University Health Truman Medical Center
Kansas City, Missouri 64108
Kansas City, Missouri 64108
Washington University School of Medicine
Saint Louis, Missouri 63110
Saint Louis, Missouri 63110
Hackensack Meridian Health
Hackensack, New Jersey 07601
Hackensack, New Jersey 07601
Rutgers, the State University of New Jersey
Piscataway, New Jersey 08854
Piscataway, New Jersey 08854
The Valley Hospital, Inc.
Ridgewood, New Jersey 07450
Ridgewood, New Jersey 07450
University of New Mexico Health Sciences Center
Albuquerque, New Mexico 87102
Albuquerque, New Mexico 87102
Presbyterian Healthcare Services
Albuquerque, New Mexico 87106
Albuquerque, New Mexico 87106
University at Buffalo
Buffalo, New York 14214
Buffalo, New York 14214
NYU Langone Health
New York, New York 10016
New York, New York 10016
Columbia University Medical Center
New York, New York 10032
New York, New York 10032
Weill Medical College of Cornell University
New York, New York 10065
New York, New York 10065
Stony Brook University
Stony Brook, New York 11794
Stony Brook, New York 11794
Westchester Medical Center
Valhalla, New York 10595
Valhalla, New York 10595
White Plains Hospital
White Plains, New York 10601
White Plains, New York 10601
University of North Carolina
Chapel Hill, North Carolina 27599
Chapel Hill, North Carolina 27599
Wake Forest Baptist Health
Winston-Salem, North Carolina 27157
Winston-Salem, North Carolina 27157
The Lindner Center for Research and Education at The Christ Hospital
Cincinnati, Ohio 45219
Cincinnati, Ohio 45219
University of Cincinnati College of Medicine
Cincinnati, Ohio 45267
Cincinnati, Ohio 45267
Ohio State University Medical Center
Columbus, Ohio 43210
Columbus, Ohio 43210
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma 73104
Oklahoma City, Oklahoma 73104
Thomas Jefferson University
Philadelphia, Pennsylvania 19144
Philadelphia, Pennsylvania 19144
Allegheny Singer Research Institute
Pittsburgh, Pennsylvania 15212
Pittsburgh, Pennsylvania 15212
Penn State Health Medical Group Berks Cardiology
Wyomissing, Pennsylvania 19610
Wyomissing, Pennsylvania 19610
Rhode Island Hospital
Providence, Rhode Island 02903
Providence, Rhode Island 02903
Medical University of South Carolina
Charleston, South Carolina 29425
Charleston, South Carolina 29425
MUSC Health Heart and Vascular
Columbia, South Carolina 29204
Columbia, South Carolina 29204
Texas Cardiac Arrhythmia Research Foundation
Austin, Texas 78705
Austin, Texas 78705
University of Texas Southwestern Medical Center
Dallas, Texas 75390
Dallas, Texas 75390
Houston Methodist Hospital
Houston, Texas 77030
Houston, Texas 77030
University of Texas Health Science Center at Houston
Houston, Texas 77030
Houston, Texas 77030
University of Virginia
Charlottesville, Virginia 22903
Charlottesville, Virginia 22903
Virginia Commonwealth University
Richmond, Virginia 23284
Richmond, Virginia 23284
St. Joseph Medical Center Tacoma
Tacoma, Washington 98405
Tacoma, Washington 98405
Medical College of Wisconsin Froedtert Hospital
Milwaukee, Wisconsin 53226
Milwaukee, Wisconsin 53226
More Details
- NCT ID
- NCT05836987
- Status
- Recruiting
- Sponsor
- Johns Hopkins University
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.