The Rhythm Evaluation for AntiCoagulaTion With Continuous Monitoring of Atrial Fibrillation

Atrial Fibrillation Clinical Trial

— REACT-AF  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05836987
• Other study ID #: IRB00354588
• Secondary ID: 1U24HL165066-01
• Status: Recruiting
• Phase: Phase 3
• Start date: July 13, 2023
• Est. completion date: July 31, 2029

Study information

• Verified date: June 2024
• Source: Johns Hopkins University
• Contact: Nicole Odenwald
• Phone: 650-725-3187
• Email: nicoleod[@]stanford.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 5350
• Est. completion date: July 31, 2029
• Est. primary completion date: July 31, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 22 Years to 85 Years

Eligibility

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)

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

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.

Drug:
• Continuous DOAC therapy
DOACs will be prescribed to patients according to the treating healthcare provider(s) according to labeling instructions.

Locations

Country	Name	City	State
United States	Presbyterian Healthcare Services	Albuquerque	New Mexico
United States	University of New Mexico Health Sciences Center	Albuquerque	New Mexico
United States	Emory University	Atlanta	Georgia
United States	University of Colorado	Aurora	Colorado
United States	Texas Cardiac Arrhythmia Research Foundation	Austin	Texas
United States	Johns Hopkins Univeristy	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Boston Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	University at Buffalo	Buffalo	New York
United States	Lahey Hospital & Medical Center	Burlington	Massachusetts
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	Loyola University 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	University of Illinois Chicago	Chicago	Illinois
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	BayCare Health Systems	Clearwater	Florida
United States	MUSC Health Heart and Vascular	Columbia	South Carolina
United States	Ohio State University Medical Center	Columbus	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Henry Ford Health	Detroit	Michigan
United States	Essentia Health The Duluth Clinic	Duluth	Minnesota
United States	Alexian Brothers Health System	Elk Grove Village	Illinois
United States	NorthShore University HealthSystem	Evanston	Illinois
United States	University of Florida	Gainesville	Florida
United States	Corewell Health (Former Spectrum Health)	Grand Rapids	Michigan
United States	Trinity Health Grand Rapids/Mercy Health	Grand Rapids	Michigan
United States	Hackensack Meridian Health	Hackensack	New Jersey
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	Ascension St. Vincent	Indianapolis	Indiana
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Mayo Clinic	Jacksonville	Florida
United States	University Health Truman Medical Center	Kansas City	Missouri
United States	South Denver Cardiology Associates, P.C.	Littleton	Colorado
United States	University of California Los Angeles (UCLA Health)	Los Angeles	California
United States	University of Southern California - Keck School of Medicine	Los Angeles	California
United States	University of Wisconsin	Madison	Wisconsin
United States	Medical College of Wisconsin Froedtert Hospital	Milwaukee	Wisconsin
United States	University of Minnesota	Minneapolis	Minnesota
United States	Midwest Cardiovascular Institute	Naperville	Illinois
United States	Columbia University Medical Center	New York	New York
United States	NYU Langone Health	New York	New York
United States	Weill Medical College of Cornell University	New York	New York
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Rutgers, the State University of New Jersey	Piscataway	New Jersey
United States	Allegheny Singer Research Institute	Pittsburgh	Pennsylvania
United States	Rhode Island Hospital	Providence	Rhode Island
United States	NewYork Presbyterian - Queens	Queens	New York
United States	Virginia Commonwealth University	Richmond	Virginia
United States	The Valley Hospital, Inc.	Ridgewood	New Jersey
United States	William Beaumont Hospital	Royal Oak	Michigan
United States	UC Davis Health	Sacramento	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Scripps Health	San Diego	California
United States	Sarasota Memorial Health Care System	Sarasota	Florida
United States	Maine Medical Partners MaineHealth Cardiology	Scarborough	Maine
United States	Stanford University	Stanford	California
United States	St. Joseph Medical Center Tacoma	Tacoma	Washington
United States	Westchester Medical Center	Valhalla	New York
United States	Georgia Arrhythmia Consultants and Research Institute	Warner Robins	Georgia
United States	Medical Faculty Associates George Washington University	Washington	District of Columbia
United States	St. Elizabeth's Medical Center	Washington	District of Columbia
United States	White Plains Hospital	White Plains	New York
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina
United States	Wooster Community Hospital	Wooster	Ohio
United States	UMass Chan Medical School	Worcester	Massachusetts
United States	Penn State Health Medical Group Berks Cardiology	Wyomissing	Pennsylvania
United States	Trinity Health Michigan Heart - Ann Arbor	Ypsilanti	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
Johns Hopkins University	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	To assess whether AFSW-guided, time-delimited DOAC therapy significantly reduces major bleeding events compared to continuous DOAC therapy.	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