The Rhythm Evaluation for AntiCoagulaTion With Continuous Monitoring of Atrial Fibrillation (REACT-AF)

March 12, 2024 updated by: Johns Hopkins University

REACT-AF: Rhythm Evaluation for AntiCoagulaTion With Continuous Monitoring of Atrial Fibrillation

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 (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.

Study Type

Interventional

Enrollment (Estimated)

5350

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90033
        • Not yet recruiting
        • University of Southern California - Keck School of Medicine
        • Principal Investigator:
          • Junaid Zaman, MD
        • Contact:
        • Contact:
      • Los Angeles, California, United States, 90095
      • Sacramento, California, United States, 95817
        • Recruiting
        • UC Davis Health
        • Contact:
        • Principal Investigator:
          • Uma Srivatsa
      • San Diego, California, United States, 92103
      • Stanford, California, United States, 94305
        • Recruiting
        • Stanford University
        • Contact:
        • Principal Investigator:
          • Alexander Perino
    • Colorado
      • Aurora, Colorado, United States, 80045
      • Littleton, Colorado, United States, 80120
        • Recruiting
        • South Denver Cardiology Associates, P.C.
        • Contact:
        • Principal Investigator:
          • Srikanth Sundaram
    • District of Columbia
      • Washington, District of Columbia, United States, 20032
        • Recruiting
        • St. Elizabeth's Medical Center
        • Contact:
        • Principal Investigator:
          • John Wylie
      • Washington, District of Columbia, United States, 20037
        • Recruiting
        • Medical Faculty Associates George Washington University
        • Contact:
        • Contact:
        • Principal Investigator:
          • Allen Solomon
    • Florida
      • Clearwater, Florida, United States, 33759
        • Recruiting
        • Baycare Health systems
        • Contact:
        • Principal Investigator:
          • Kevin Makati
      • Gainesville, Florida, United States, 32611
      • Jacksonville, Florida, United States, 32224
        • Not yet recruiting
        • Mayo Clinic
        • Contact:
        • Principal Investigator:
          • Andrew Tseng, MD
      • Sarasota, Florida, United States, 34236
        • Recruiting
        • Sarasota Memorial Health Care System
        • Contact:
        • Principal Investigator:
          • Smirti Banthia, MD
    • Georgia
      • Atlanta, Georgia, United States, 30332
        • Recruiting
        • Emory University
        • Contact:
        • Contact:
          • Jovita Brevard
          • Phone Number: jovita.johnson@emory.edu
        • Principal Investigator:
          • Michael Lloyd
      • Warner Robins, Georgia, United States, 31093
        • Recruiting
        • Georgia Arrhythmia Consultants and Research Institute
        • Contact:
        • Principal Investigator:
          • Feliz Sogade, MD
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Recruiting
        • Rush University Medical Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • Annabelle Volgman, MD
      • Chicago, Illinois, United States, 60637
      • Chicago, Illinois, United States, 60611
      • Chicago, Illinois, United States, 60660
        • Recruiting
        • Loyola University Chicago
        • Contact:
        • Contact:
        • Principal Investigator:
          • Peter Santucci, MD
      • Chicago, Illinois, United States, 60607
        • Recruiting
        • University of Illinois Chicago
        • Contact:
        • Principal Investigator:
          • Dana Johnson
        • Contact:
      • Elk Grove Village, Illinois, United States, 60007
        • Recruiting
        • Alexian Brothers Health System
        • Principal Investigator:
          • Taral Patel, MD
        • Contact:
        • Contact:
      • Evanston, Illinois, United States, 60201
        • Not yet recruiting
        • NorthShore University HealthSystem
        • Contact:
        • Principal Investigator:
          • Jeremiah Wasserlauf, MD
      • Naperville, Illinois, United States, 60540
        • Recruiting
        • Midwest Cardiovascular Institute
        • Contact:
        • Principal Investigator:
          • Moeen Saleem
    • Indiana
      • Indianapolis, Indiana, United States, 46260
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Recruiting
        • University of Iowa Hospitals and Clinics
        • Contact:
        • Principal Investigator:
          • Samuel Johnston
    • Maine
      • Scarborough, Maine, United States, 04074
    • Maryland
      • Baltimore, Maryland, United States, 21218
        • Recruiting
        • Johns Hopkins Univeristy
        • Contact:
        • Principal Investigator:
          • Hugh Calkins
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Beth Israel Deaconess Medical Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • Peter Zimetbaum, MD
      • Boston, Massachusetts, United States, 02118
        • Recruiting
        • Boston Medical Center
        • Contact:
        • Principal Investigator:
          • Robert Helm
      • Boston, Massachusetts, United States, 02111
        • Recruiting
        • Tufts Medical Center
        • Contact:
        • Principal Investigator:
          • Christopher Madias, MD
      • Burlington, Massachusetts, United States, 01805
        • Recruiting
        • Lahey Hospital & Medical Center
        • Contact:
        • Principal Investigator:
          • Matthew Reynolds
      • Worcester, Massachusetts, United States, 01655
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Recruiting
        • Henry Ford Health
        • Contact:
        • Contact:
        • Principal Investigator:
          • Marc Lahiri
      • Grand Rapids, Michigan, United States, 49503
      • Grand Rapids, Michigan, United States, 49503
      • Royal Oak, Michigan, United States, 48073
      • Ypsilanti, Michigan, United States, 48197
    • Minnesota
      • Duluth, Minnesota, United States, 55812
      • Minneapolis, Minnesota, United States, 55455
        • Not yet recruiting
        • University of Minnesota
        • Contact:
        • Contact:
        • Principal Investigator:
          • Lin Yee Chen, MD
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Recruiting
        • University Health Truman Medical Center
        • Contact:
        • Principal Investigator:
          • Paramdeep Baweja, MD
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine
        • Contact:
        • Principal Investigator:
          • Thomas Maddox, MD
        • Contact:
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Recruiting
        • Hackensack Meridian Health
        • Contact:
        • Principal Investigator:
          • Tanya Glotzer
      • Piscataway, New Jersey, United States, 08854
        • Recruiting
        • Rutgers, The State University of New Jersey
        • Principal Investigator:
          • Partho Sengupta
        • Contact:
        • Contact:
      • Ridgewood, New Jersey, United States, 07450
        • Recruiting
        • The Valley Hospital, Inc.
        • Principal Investigator:
          • Suneet Mittal
        • Contact:
    • New Mexico
      • Albuquerque, New Mexico, United States, 87102
        • Recruiting
        • University of New Mexico Health Sciences Center
        • Contact:
        • Principal Investigator:
          • Abinash Achrekar, MD
      • Albuquerque, New Mexico, United States, 87106
        • Recruiting
        • Presbyterian Healthcare Services
        • Principal Investigator:
          • Michael West, MD
        • Contact:
        • Contact:
    • New York
      • Buffalo, New York, United States, 14214
        • Recruiting
        • University at Buffalo
        • Contact:
        • Contact:
        • Principal Investigator:
          • Anne Curtis, MD
      • New York, New York, United States, 10016
      • New York, New York, United States, 10032
        • Recruiting
        • Columbia University Medical Center
        • Contact:
        • Principal Investigator:
          • Angelo Biviano
      • New York, New York, United States, 10065
        • Recruiting
        • Weill Medical College of Cornell University
        • Contact:
        • Principal Investigator:
          • Jim Cheung, MD
        • Contact:
          • Penn Collins
          • Phone Number: gpc4001@med.cornell.edu
      • Queens, New York, United States, 11355
        • Recruiting
        • NewYork Presbyterian - Queens
        • Principal Investigator:
          • Joon Hyuk Kim
        • Contact:
      • Valhalla, New York, United States, 10595
      • White Plains, New York, United States, 10601
        • Recruiting
        • White Plains Hospital
        • Contact:
        • Principal Investigator:
          • James Peacock
        • Contact:
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • Recruiting
        • University of North Carolina
        • Contact:
        • Principal Investigator:
          • Anil Gehi, MD
      • Winston-Salem, North Carolina, United States, 27157
        • Recruiting
        • Wake Forest Baptist Health
        • Principal Investigator:
          • Prashant Bhave
        • Contact:
    • Ohio
      • Cincinnati, Ohio, United States, 45267
        • Recruiting
        • University of Cincinnati College of Medicine
        • Contact:
        • Contact:
        • Principal Investigator:
          • Richard Becker
      • Cincinnati, Ohio, United States, 45219
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • Ohio State University Medical Center
        • Principal Investigator:
          • Salvatore Savona, MD
        • Contact:
      • Wooster, Ohio, United States, 44691
        • Recruiting
        • Wooster Community Hospital
        • Contact:
        • Principal Investigator:
          • Cyril Ofori, MD
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15212
      • Wyomissing, Pennsylvania, United States, 19610
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Not yet recruiting
        • Rhode Island Hospital
        • Contact:
        • Principal Investigator:
          • Estelle Torbey, MD
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Recruiting
        • Medical University of South Carolina
        • Contact:
        • Principal Investigator:
          • Rachel Kaplan
      • Columbia, South Carolina, United States, 29204
        • Not yet recruiting
        • MUSC Health Heart and Vascular
        • Contact:
        • Principal Investigator:
          • Venkateshwar Gottipaty, MD
    • Texas
      • Austin, Texas, United States, 78705
        • Recruiting
        • Texas Cardiac Arrhythmia Research Foundation
        • Contact:
        • Principal Investigator:
          • Amin Al Ahmad
      • Dallas, Texas, United States, 75390
        • Recruiting
        • University of Texas Southwestern Medical Center
        • Contact:
        • Principal Investigator:
          • Mark Link, MD
      • Houston, Texas, United States, 77030
        • Recruiting
        • University of Texas Health Science Center at Houston
        • Contact:
        • Principal Investigator:
          • Ijeoma Ekeruo, MD
      • Houston, Texas, United States, 77030
        • Not yet recruiting
        • Houston Methodist Hospital
        • Principal Investigator:
          • Miguel Valderrabano, MD
        • Contact:
      • Houston, Texas, United States, 77030
        • Not yet recruiting
        • Baylor College of Medicine
        • Principal Investigator:
          • Mihail Chelu, MD
        • Contact:
    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • Recruiting
        • University of Virginia
        • Contact:
        • Principal Investigator:
          • Rohit Malhotra
      • Richmond, Virginia, United States, 23284
    • Washington
      • Tacoma, Washington, United States, 98405
        • Not yet recruiting
        • St. Joseph Medical Center Tacoma
        • Contact:
        • Principal Investigator:
          • Gopi Dandamudi
    • Wisconsin
      • Madison, Wisconsin, United States, 53706
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Medical College of Wisconsin Froedtert Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Jason Rubenstein

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Male or female, 22-85 years of age.
  2. English speaking participants*
  3. Documented history of symptomatic or asymptomatic paroxysmal or persistent AF. The duration of AF must have been > 30 seconds as documented by an external monitor or present on 12-lead ECG.
  4. CHA2DS2-VASC score of 1-4 without prior stroke or Transient Ischemic Attack (TIA)**
  5. The participant is on a DOAC at the time of screening.

  6. Willing and able to comply with the protocol, including:

    • Possession of a smartwatch-compatible smartphone (iPhone that supports the latest shipping iOS) with a cellular service plan
    • Be willing to wear the Apple watch at least 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, nursing, or of child-bearing potential and is not on birth control.
  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.
  6. Any documented single AF episode lasting ≥ 1 hour on screening external cardiac monitor of >=6 days duration.
  7. Mechanical prosthetic valve(s) or severe valve disease.
  8. Hypertrophic cardiomyopathy.
  9. Participant needs Direct Oral Anticoagulation (DOAC) for reasons other than preventing stroke or arterial embolism resulting from AF (i.e., preventing Deep Vein Thrombosis (DVT) or Pulmonary Embolism (PE)) or needs permanent Oral Anticoagulant (OAC) (i.e., congenital heart defects, prosthetic heart valve).
  10. Participants deemed high risk for non-cardioembolic stroke (i.e., significant carotid artery disease defined as stenosis > 75%) based on the investigator's discretion.
  11. 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.
  12. The participant has a tattoo, birthmark, or surgical scar over the dorsal wrist area on the ipsilateral side that the AFSW may be worn.
  13. The participant has a tremor on their ipsilateral side that the AFSW may be worn.
  14. Any concomitant condition that, in the investigator's opinion, would not allow safe participation in the study (e.g., drug addiction, alcohol abuse).
  15. Known hypersensitivity or contraindication to direct oral anticoagulants.
  16. Documented prior stroke (ischemic or hemorrhagic) or transient ischemic attack.
  17. Reversible causes of AF (e.g., cardiac surgery, pulmonary embolism, untreated hyperthyroidism). AF ablation does not constitute reversible AF.
  18. > 5% burden premature atrial or ventricular depolarizations on any given calendar day on pre-enrollment cardiac monitoring.
  19. History of atrial flutter that has not been treated with ablation (participants in atrial flutter and have been ablated are eligible for enrollment).
  20. Stage 4 or 5 chronic kidney disease.

  21. Conditions associated with an increased risk of bleeding:

    • Major surgery in the previous month
    • Planned surgery or intervention in the next three months.
    • 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
    • Required use of non-aspirin antiplatelet agents (i.e., Plavix) at time of enrollment

    • Uncontrolled hypertension (Systolic Blood Pressure (SBP) >180 mmHg and/or Diastolic Blood Pressure( DBP) >100 mmHg)

      • Spanish-only speakers may be included in the future at select sites where consent forms are appropriately translated.

        • 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%

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
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.
Other Names:
  • Apple Watch
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.
Drug: Continuous DOAC therapy
DOACs will be prescribed to patients according to the treating healthcare provider(s) according to labeling instructions.
Other Names:
  • Oral Anticoagulation therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Time Frame: 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.
At 60 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To assess whether AFSW-guided, time-delimited DOAC therapy significantly reduces major bleeding events compared to continuous DOAC therapy.
Time Frame: 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.
At 60 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Johns Hopkins University

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

  • Principal Investigator: Rod Passman, Northwestern University
  • Principal Investigator: Dan Hanley, Johns Hopkins University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 13, 2023

Primary Completion (Estimated)

July 31, 2029

Study Completion (Estimated)

July 31, 2029

Study Registration Dates

First Submitted

April 19, 2023

First Submitted That Met QC Criteria

April 19, 2023

First Posted (Actual)

May 1, 2023

Study Record Updates

Last Update Posted (Actual)

March 13, 2024

Last Update Submitted That Met QC Criteria

March 12, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00354588
  • 1U24HL165066-01 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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