U24HL165066

2/2 REACT-AF: Rhythm Evaluation for Anticoagulation with Continuous Monitoring of Atrial Fibrillation - Project Summary / Abstract

Purpose:
The Rhythm Evaluation for Anticoagulation with Continuous Monitoring of Atrial Fibrillation (REACT AF) clinical trial will compare the efficacy and safety of two treatment strategies for stroke prevention in atrial fibrillation (AF): the current standard of continuous direct oral anticoagulation (DOAC) versus a novel strategy of precision, time-delimited DOAC initiated only in response to a 1-hour AF episode detected by an AF-sensing smartwatch (AFSW - Apple Watch).

Rationale:
Stroke risk is often temporally related to AF onset and duration, but bleeding risk continues as a constant risk of anticoagulation exposure even during long AF-free periods when stroke risk may be low. REACT-AF will evaluate the benefits and risks of withholding anticoagulation during prolonged periods of sinus rhythm as guided by an AFSW. Compared with continuous DOAC, AFSW-guided, time-delimited DOAC treatment may reduce bleeding events while maintaining stroke protection. This has the potential to improve important major clinical outcomes and quality of life while reducing healthcare utilization.

Design:
REACT-AF is a multicenter prospective, randomized, open-label, blinded endpoint (probe design) trial comparing the current standard of care of continuous DOAC administration versus time-delimited DOAC treatment guided by an AFSW in patients with a history of paroxysmal or persistent AF and low-to-moderate stroke risk (CHA2DS2-VASC score 1-4). The study will have an initial explanatory Phase I followed by an explanatory Phase II with pragmatic elements.

Primary Aim 1 (Efficacy Objective):
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

Hypothesis:
Time-delimited DOAC therapy is non-inferior to continuous DOAC therapy for the composite endpoint of ischemic stroke, systemic embolism, and all-cause mortality.

Primary Aim 2 (Safety Objective):
To assess whether AFSW-guided, time-delimited DOAC therapy significantly reduces major bleeding events compared to continuous DOAC therapy.

Hypothesis:
Major bleeding events will be significantly lower in participants randomized to AFSW-guided, time-delimited DOAC therapy compared with participants receiving continuous DOAC therapy.

Exploratory Aim 1:
To compare overall participant satisfaction with anticoagulation management between the two study arms.

Exploratory Aim 2:
To compare estimates of health-related resource utilization in participants randomized to control versus experimental arms.

The Johns Hopkins University

TO FOSTER HEART AND VASCULAR RESEARCH IN THE BASIC, TRANSLATIONAL, CLINICAL AND POPULATION SCIENCES, AND TO FOSTER TRAINING TO BUILD TALENTED YOUNG INVESTIGATORS IN THESE AREAS, FUNDED THROUGH COMPETITIVE RESEARCH TRAINING GRANTS. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, USE SMALL BUSINESS TO MEET FEDERAL RESEARCH AND DEVELOPMENT NEEDS, FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY SOCIALLY AND ECONOMICALLY DISADVANTAGED PERSONS, AND INCREASE PRIVATE-SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE R&D BETWEEN SMALL BUSINESSES AND RESEARCH INSTITUTIONS, AND INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL R&D.

93.853 - Extramural Research Programs in the Neurosciences and Neurological Disorders

National Heart Lung and Blood Institute (NHLBI) [HHS - NIH]

National Institute of Neurological Disorders and Stroke (NNDS) [HHS - NIH]

Baltimore, Maryland 212051832 United States

Single Zip Code

Data Coordinating Center for Multi-Site Investigator-Initiated Clinical Trials (Collaborative U24 Clinical Trial Required) (PAR-19-330)

Amendment Since initial award the total obligations have increased 228% from $1,839,921 to $6,043,000.