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

Sponsor

Johns Hopkins University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05836987

Collaborator

National Heart, Lung, and Blood Institute (NHLBI) (NIH)

5,350

Enrollment

Locations

Arms

73.5

Anticipated Duration (Months)

214

Patients Per Site

2.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation	Device: AFSW Guided DOAC Drug: Continuous DOAC therapy	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

5350 participants

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.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.

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.

Primary Purpose:

Prevention

Official Title:

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

Anticipated Study Start Date :

Jun 15, 2023

Anticipated Primary Completion Date :

Jul 31, 2029

Anticipated Study Completion Date :

Jul 31, 2029

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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. [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.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

22 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female, 22-85 years of age.
English speaking participants*
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.
CHA2DS2-VASC score of 1-4 without prior stroke or Transient Ischemic Attack (TIA)**
The participant is on a DOAC at the time of screening.
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

Willing and able to discontinue DOAC
The participant is willing and able to provide informed consent.

Exclusion Criteria:

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, nursing, or of child-bearing potential and is not on birth control.
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.
Any documented single AF episode lasting ≥ 1 hour on screening external cardiac monitor of > 7 days duration.
Mechanical prosthetic valve(s) or severe valve disease.
Hypertrophic cardiomyopathy.
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).
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.
Any concomitant condition that, in the investigator's opinion, would not allow safe participation in the study (e.g., drug addiction, alcohol abuse).
Known hypersensitivity or contraindication to direct oral anticoagulants.
Documented prior stroke (ischemic or hemorrhagic) or transient ischemic attack.
Reversible causes of AF (e.g., cardiac surgery, pulmonary embolism, untreated hyperthyroidism). AF ablation does not constitute reversible AF.
5% burden premature atrial or ventricular depolarizations on any given calendar day on pre-enrollment cardiac monitoring.
History of atrial flutter that has not been treated with ablation (participants in atrial flutter and have been ablated are eligible for enrollment).
Stage 4 or 5 chronic kidney disease.
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%

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University	Stanford	California	United States	94305
2	South Denver Cardiology Associates, P.C.	Littleton	Colorado	United States	80120
3	St. Elizabeth's Medical Center	Washington	District of Columbia	United States	20032
4	Medical Faculty Associates George Washington University	Washington	District of Columbia	United States	20037
5	BayCare Health Systems	Clearwater	Florida	United States	33759
6	Ascension St. Vincent	Indianapolis	Indiana	United States	46260
7	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
8	Boston Medical Center	Boston	Massachusetts	United States	02118
9	Lahey Hospital & Medical Center	Burlington	Massachusetts	United States	01805
10	Henry Ford Health	Detroit	Michigan	United States	48202
11	Corewell Health (Former Spectrum Health)	Grand Rapids	Michigan	United States	49503
12	William Beaumont Hospital	Royal Oak	Michigan	United States	48073
13	Rutgers, the State University of New Jersey	Piscataway	New Jersey	United States	08854
14	The Valley Hospital, Inc.	Ridgewood	New Jersey	United States	07450
15	Columbia University Medical Center	New York	New York	United States	10032
16	NewYork Presbyterian - Queens	Queens	New York	United States	11355
17	Westchester Medical Center	Valhalla	New York	United States	10595
18	White Plains Hospital	White Plains	New York	United States	10601
19	Moses H. Cone Memorial Hospital	Greensboro	North Carolina	United States	27401
20	Wake Forest Baptist Health	Winston-Salem	North Carolina	United States	27157
21	Lankenau Institute for Medical Research	Philadelphia	Pennsylvania	United States	19096
22	Allegheny Singer Research Institute	Pittsburgh	Pennsylvania	United States	15212
23	Texas Cardiac Arrhythmia Research Foundation	Austin	Texas	United States	78705
24	University of Texas Southwestern Medical	Dallas	Texas	United States	75390
25	Virginia Commonwealth University	Richmond	Virginia	United States	23284