NCT05836987

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
5,350

participants targeted

Target at P75+ for phase_3 atrial-fibrillation

Timeline
39mo left

Started Jul 2023

Longer than P75 for phase_3 atrial-fibrillation

Geographic Reach
1 country

93 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress47%
Jul 2023Jul 2029

First Submitted

Initial submission to the registry

April 19, 2023

Completed
12 days until next milestone

First Posted

Study publicly available on registry

May 1, 2023

Completed
2 months until next milestone

Study Start

First participant enrolled

July 13, 2023

Completed
6.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 31, 2029

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 31, 2029

Last Updated

April 9, 2026

Status Verified

April 1, 2026

Enrollment Period

6.1 years

First QC Date

April 19, 2023

Last Update Submit

April 7, 2026

Conditions

Keywords

Atrial FibrillationAnticoagulationAF-sensing Smart WatchIschemic StrokeSystemic Embolism

Outcome Measures

Primary Outcomes (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.

    At 60 months

Secondary Outcomes (1)

  • To assess whether AFSW-guided, time-delimited DOAC therapy significantly reduces major bleeding events compared to continuous DOAC therapy.

    At 60 months

Study Arms (2)

AFSW Guided DOAC

EXPERIMENTAL

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

Continuous DOAC therapy

ACTIVE COMPARATOR

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

Interventions

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.

Also known as: Apple Watch
AFSW Guided DOAC

DOACs will be prescribed to patients according to the treating healthcare provider(s) according to labeling instructions.

Also known as: Oral Anticoagulation therapy
Continuous DOAC therapy

Eligibility Criteria

Age22 Years - 85 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • years of age.
  • English speaking participants. Spanish-only speakers may be included in the future at select sites appropriately translated.
  • History of non-permanent atrial fibrillation.
  • 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%.
  • The participant is on a DOAC at the time of screening and willing to stay on DOAC for duration of study.
  • 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
  • Willing and able to discontinue DOAC
  • The participant is willing and able to provide informed consent.

You may not qualify if:

  • Valvular or permanent atrial fibrillation.
  • Current treatment with warfarin and unwilling or unable to take a DOAC.
  • The participant is a woman who is pregnant or nursing.
  • 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.
  • 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.
  • Known or suspected symptomatic or asymptomatic atrial fibrillation lasting ≥ 1 hour/month over the last 3 months.
  • Ablation for AF within the last 2 months.
  • Prior or anticipated left atrial appendage occlusion or ligation.
  • Mechanical prosthetic valve(s) or severe valve disease.
  • Hypertrophic cardiomyopathy.
  • 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).
  • Participants deemed high risk for non-cardioembolic stroke (i.e., significant carotid artery disease defined as stenosis \> 75%) based on the investigator's discretion.
  • 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.
  • The participant has a tattoo, birthmark, or surgical scar over the dorsal wrist area on the ipsilateral side that the AFSW may be worn.
  • The participant has a tremor on their ipsilateral side that the AFSW may be worn.
  • +16 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (93)

Banner University

Phoenix, Arizona, 85006, United States

RECRUITING

University of Southern California - Keck School of Medicine

Los Angeles, California, 90033, United States

RECRUITING

University of California Los Angeles (UCLA Health)

Los Angeles, California, 90095, United States

RECRUITING

UC Davis Health

Sacramento, California, 95817, United States

RECRUITING

Scripps Health

San Diego, California, 92103, United States

RECRUITING

Kaiser Permanente

San Francisco, California, 94115, United States

NOT YET RECRUITING

Stanford University

Stanford, California, 94305, United States

RECRUITING

University of Colorado

Aurora, Colorado, 80045, United States

RECRUITING

South Denver Cardiology Associates, P.C.

Littleton, Colorado, 80120, United States

RECRUITING

St. Elizabeth's Medical Center

Washington D.C., District of Columbia, 20032, United States

RECRUITING

Medical Faculty Associates George Washington University

Washington D.C., District of Columbia, 20037, United States

WITHDRAWN

BayCare Health Systems

Clearwater, Florida, 33759, United States

RECRUITING

University of Florida

Gainesville, Florida, 32611, United States

RECRUITING

Mayo Clinic

Jacksonville, Florida, 32224, United States

RECRUITING

University of Miami - Leonard S. Miller SOM

Miami, Florida, 33136, United States

RECRUITING

Sarasota Memorial Health Care System

Sarasota, Florida, 34236, United States

RECRUITING

Cleveland Clinic Florida

Stuart, Florida, 34994, United States

WITHDRAWN

Baycare Health Systems Clearwater

Winter Haven, Florida, 33881, United States

RECRUITING

Emory University

Atlanta, Georgia, 30332, United States

RECRUITING

Georgia Arrhythmia Consultants and Research Institute

Warner Robins, Georgia, 31093, United States

RECRUITING

University of Illinois Chicago

Chicago, Illinois, 60607, United States

RECRUITING

Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

Rush University Medical Center

Chicago, Illinois, 60612, United States

RECRUITING

University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

Loyola University Chicago

Chicago, Illinois, 60660, United States

RECRUITING

Alexian Brothers Health System

Elk Grove Village, Illinois, 60007, United States

RECRUITING

NorthShore University HealthSystem

Evanston, Illinois, 60201, United States

RECRUITING

Midwest Cardiovascular Institute

Naperville, Illinois, 60540, United States

RECRUITING

Ascension St. Vincent

Indianapolis, Indiana, 46260, United States

RECRUITING

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

RECRUITING

Maine Medical Partners MaineHealth Cardiology

Scarborough, Maine, 04074, United States

RECRUITING

Johns Hopkins Univeristy

Baltimore, Maryland, 21218, United States

RECRUITING

Tufts Medical Center

Boston, Massachusetts, 02111, United States

RECRUITING

Mass General Hospital

Boston, Massachusetts, 02114, United States

NOT YET RECRUITING

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Boston Medical Center

Boston, Massachusetts, 02118, United States

RECRUITING

BMC - Brighton

Boston, Massachusetts, 02135, United States

RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

RECRUITING

Lahey Hospital & Medical Center

Burlington, Massachusetts, 01805, United States

RECRUITING

UMass Chan Medical School

Worcester, Massachusetts, 01655, United States

ACTIVE NOT RECRUITING

Henry Ford Health

Detroit, Michigan, 48202, United States

RECRUITING

Corewell Health (Former Spectrum Health)

Grand Rapids, Michigan, 49503, United States

RECRUITING

Trinity Health Grand Rapids/Mercy Health

Grand Rapids, Michigan, 49503, United States

RECRUITING

William Beaumont Hospital

Royal Oak, Michigan, 48073, United States

RECRUITING

Trinity Health Michigan Heart - Ann Arbor

Ypsilanti, Michigan, 48197, United States

RECRUITING

Essentia Health The Duluth Clinic

Duluth, Minnesota, 55812, United States

ACTIVE NOT RECRUITING

Minneapolis Heart Institute Foundation

Minneapolis, Minnesota, 55407, United States

RECRUITING

Hennepin Healthcare Research Institute

Minneapolis, Minnesota, 55415, United States

RECRUITING

University of Minnesota

Minneapolis, Minnesota, 55455, United States

RECRUITING

University Health Truman Medical Center

Kansas City, Missouri, 64108, United States

WITHDRAWN

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Advanced Heart and Vascular Institute of Hunterdon

Flemington, New Jersey, 08822, United States

RECRUITING

Hackensack Meridian Health

Hackensack, New Jersey, 07601, United States

RECRUITING

Rutgers, the State University of New Jersey

Piscataway, New Jersey, 08854, United States

RECRUITING

The Valley Hospital, Inc.

Ridgewood, New Jersey, 07450, United States

RECRUITING

University of New Mexico Health Sciences Center

Albuquerque, New Mexico, 87102, United States

RECRUITING

Presbyterian Healthcare Services

Albuquerque, New Mexico, 87106, United States

ACTIVE NOT RECRUITING

University at Buffalo

Buffalo, New York, 14214, United States

RECRUITING

NYU Langone Health

New York, New York, 10016, United States

RECRUITING

Columbia University Medical Center

New York, New York, 10032, United States

RECRUITING

Weill Medical College of Cornell University

New York, New York, 10065, United States

RECRUITING

NewYork Presbyterian - Queens

Queens, New York, 11355, United States

RECRUITING

Staten Island University Hospital-Northwell Health

Staten Island, New York, 10305, United States

RECRUITING

Stony Brook University

Stony Brook, New York, 11794, United States

RECRUITING

Westchester Medical Center

Valhalla, New York, 10595, United States

RECRUITING

White Plains Hospital

White Plains, New York, 10601, United States

RECRUITING

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

RECRUITING

The Lindner Center for Research and Education at The Christ Hospital

Cincinnati, Ohio, 45219, United States

RECRUITING

University of Cincinnati College of Medicine

Cincinnati, Ohio, 45267, United States

RECRUITING

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

RECRUITING

OhioHealth Research Institute

Columbus, Ohio, 43214, United States

RECRUITING

Wooster Community Hospital

Wooster, Ohio, 44691, United States

RECRUITING

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Cardiology Consultants of Philadelphia

Paoli, Pennsylvania, 19301, United States

NOT YET RECRUITING

Thomas Jefferson University

Philadelphia, Pennsylvania, 19144, United States

RECRUITING

Allegheny Singer Research Institute

Pittsburgh, Pennsylvania, 15212, United States

RECRUITING

Penn State Health Medical Group Berks Cardiology

Wyomissing, Pennsylvania, 19610, United States

RECRUITING

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

RECRUITING

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

RECRUITING

MUSC Health Heart and Vascular

Columbia, South Carolina, 29204, United States

RECRUITING

Texas Cardiac Arrhythmia Research Foundation

Austin, Texas, 78705, United States

RECRUITING

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

Baylor College of Medicine

Houston, Texas, 77030, United States

RECRUITING

Houston Methodist Hospital

Houston, Texas, 77030, United States

RECRUITING

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

RECRUITING

University of Utah

Salt Lake City, Utah, 84112, United States

RECRUITING

University of Virginia

Charlottesville, Virginia, 22903, United States

RECRUITING

James River Cardiology

Richmond, Virginia, 23229, United States

RECRUITING

Virginia Commonwealth University

Richmond, Virginia, 23284, United States

RECRUITING

St. Joseph Medical Center Tacoma

Tacoma, Washington, 98405, United States

RECRUITING

University of Wisconsin

Madison, Wisconsin, 53706, United States

RECRUITING

Medical College of Wisconsin Froedtert Hospital

Milwaukee, Wisconsin, 53226, United States

RECRUITING

MeSH Terms

Conditions

Atrial FibrillationIschemic Stroke

Condition Hierarchy (Ancestors)

Arrhythmias, CardiacHeart DiseasesCardiovascular DiseasesPathologic ProcessesPathological Conditions, Signs and SymptomsStrokeCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular Diseases

Study Officials

  • Rod Passman

    Northwestern University

    PRINCIPAL INVESTIGATOR
  • Dan Hanley

    Johns Hopkins University

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Masking Details
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.
Purpose
PREVENTION
Intervention Model
PARALLEL
Model Details: 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.
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 19, 2023

First Posted

May 1, 2023

Study Start

July 13, 2023

Primary Completion (Estimated)

July 31, 2029

Study Completion (Estimated)

July 31, 2029

Last Updated

April 9, 2026

Record last verified: 2026-04

Locations