Clinical trial NCT05836987: The Rhythm Evaluation for AntiCoagulaTion With Continuous Monitoring of Atrial Fibrillation
Official title: REACT-AF: Rhythm Evaluation for AntiCoagulaTion With Continuous Monitoring of Atrial Fibrillation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Atrial Fibrillation
Keywords: Atrial Fibrillation
Anticoagulation
AF-sensing Smart Watch
Ischemic Stroke
Systemic Embolism
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2023-05-01
Enrollment: 5350
Sex: ALL
Minimum age (years): 22
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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

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.

Eligibility criteria: 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)

Primary outcomes:
measure: 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.
timeFrame: At 60 months
Secondary outcomes:
measure: To assess whether AFSW-guided, time-delimited DOAC therapy significantly reduces major bleeding events compared to continuous DOAC therapy.
timeFrame: At 60 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Banner University
state: Arizona
city: Los Angeles
country: United States
facility: University of Southern California - Keck School of Medicine
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles (UCLA Health)
state: California
city: Sacramento
country: United States
facility: UC Davis Health
state: California
city: San Diego
country: United States
facility: Scripps Health
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Littleton
country: United States
facility: South Denver Cardiology Associates, P.C.
state: Colorado
city: Washington
country: United States
facility: St. Elizabeth's Medical Center
state: District of Columbia
city: Washington
country: United States
facility: Medical Faculty Associates George Washington University
state: District of Columbia
city: Clearwater
country: United States
facility: BayCare Health Systems
state: Florida
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Miami
country: United States
facility: University of Miami - Leonard S. Miller SOM
state: Florida
city: Sarasota
country: United States
facility: Sarasota Memorial Health Care System
state: Florida
city: Stuart
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Winter Haven
country: United States
facility: Baycare Health Systems Clearwater
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Warner Robins
country: United States
facility: Georgia Arrhythmia Consultants and Research Institute
state: Georgia
city: Chicago
country: United States
facility: University of Illinois Chicago
state: Illinois
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Chicago
country: United States
facility: Loyola University Chicago
state: Illinois
city: Elk Grove Village
country: United States
facility: Alexian Brothers Health System
state: Illinois
city: Evanston
country: United States
facility: NorthShore University HealthSystem
state: Illinois
city: Naperville
country: United States
facility: Midwest Cardiovascular Institute
state: Illinois
city: Indianapolis
country: United States
facility: Ascension St. Vincent
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Scarborough
country: United States
facility: Maine Medical Partners MaineHealth Cardiology
state: Maine
city: Baltimore
country: United States
facility: Johns Hopkins Univeristy
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Hospital & Medical Center
state: Massachusetts
city: Worcester
country: United States
facility: UMass Chan Medical School
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health
state: Michigan
city: Grand Rapids
country: United States
facility: Corewell Health (Former Spectrum Health)
state: Michigan
city: Grand Rapids
country: United States
facility: Trinity Health Grand Rapids/Mercy Health
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Ypsilanti
country: United States
facility: Trinity Health Michigan Heart - Ann Arbor
state: Michigan
city: Duluth
country: United States
facility: Essentia Health The Duluth Clinic
state: Minnesota
city: Minneapolis
country: United States
facility: Hennepin Healthcare Research Institute
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: University Health Truman Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Hackensack
country: United States
facility: Hackensack Meridian Health
state: New Jersey
city: Piscataway
country: United States
facility: Rutgers, the State University of New Jersey
state: New Jersey
city: Ridgewood
country: United States
facility: The Valley Hospital, Inc.
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Health Sciences Center
state: New Mexico
city: Albuquerque
country: United States
facility: Presbyterian Healthcare Services
state: New Mexico
city: Buffalo
country: United States
facility: University at Buffalo
state: New York
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Weill Medical College of Cornell University
state: New York
city: Queens
country: United States
facility: NewYork Presbyterian - Queens
state: New York
city: Staten Island
country: United States
facility: Staten Island University Hospital-Northwell Health
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University
state: New York
city: Valhalla
country: United States
facility: Westchester Medical Center
state: New York
city: White Plains
country: United States
facility: White Plains Hospital
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Cincinnati
country: United States
facility: The Lindner Center for Research and Education at The Christ Hospital
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati College of Medicine
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Wooster
country: United States
facility: Wooster Community Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny Singer Research Institute
state: Pennsylvania
city: Wyomissing
country: United States
facility: Penn State Health Medical Group Berks Cardiology
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Columbia
country: United States
facility: MUSC Health Heart and Vascular
state: South Carolina
city: Austin
country: United States
facility: Texas Cardiac Arrhythmia Research Foundation
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Tacoma
country: United States
facility: St. Joseph Medical Center Tacoma
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Froedtert Hospital
state: Wisconsin
Study officials:
affiliation: Northwestern University
name: Rod Passman
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins University
name: Dan Hanley
role: PRINCIPAL_INVESTIGATOR
References: