Smartwatch-Guided DOAC Therapy for Atrial Fibrillation

(REACT-AF Trial)

Recruiting at 95 trial locations

Overseen By Dawood Darbar

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Johns Hopkins University

Must be taking: DOACs

Must not be taking: Warfarin, Aspirin, NSAIDs

Disqualifiers: Valvular AF, Pregnancy, Hypertrophic cardiomyopathy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 60 months

5350 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method of medication use for individuals with atrial fibrillation (AF), an irregular heartbeat. It compares standard continuous medication with a novel approach that uses a smartwatch to monitor heart rhythm and guide medication timing. This method, called AFSW Guided DOAC therapy, involves direct oral anticoagulants like Eliquis (Apixaban). Individuals with a history of non-permanent AF and a low-to-moderate risk of stroke may qualify. Participants need a smartphone compatible with a smartwatch and must be willing to wear the smartwatch most of the day. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

Participants must be willing to stop taking their current Direct Oral Anticoagulant (DOAC) medication for the study. If you are on other medications like aspirin or NSAIDs, you may need to stop them if they are not within current medical guidelines.

What prior data suggests that this smartwatch-guided DOAC therapy is safe for atrial fibrillation patients?

Research shows that the Direct Oral Anticoagulant (DOAC) treatment used in this trial is generally well-tolerated. Apixaban, a type of DOAC, is known for its safety in people and has a lower risk of causing serious brain bleeding compared to older treatments like warfarin. This suggests that the DOAC treatment, whether guided by the smartwatch or taken continuously, is likely safe for participants.

The trial is in a late stage, indicating that extensive safety testing has already occurred. This stage focuses more on confirming safety and effectiveness. While no treatment is without risk, the available data supports the safety of this therapy for people with atrial fibrillation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the Smartwatch-Guided DOAC Therapy for atrial fibrillation because it introduces a tech-savvy twist to managing this condition. Unlike standard treatments, which involve continuous medication, this method uses an AFSW linked to an Apple Watch to monitor heart rhythm irregularities and notify users of potential issues. This allows for more personalized and potentially reduced medication use, as treatment adjustments can be made based on real-time data. By leveraging wearable technology, this approach aims to enhance patient engagement and potentially improve outcomes with more timely interventions.

What evidence suggests that this trial's treatments could be effective for Atrial Fibrillation?

Research has shown that using a smartwatch to guide certain blood thinners, known as Direct Oral Anticoagulants (DOACs), might be as effective as traditional ones like warfarin for treating Atrial Fibrillation (AF). In this trial, participants in the AFSW Guided DOAC arm will use a smartwatch to intermittently and passively monitor for rhythm irregularities consistent with AF, adjusting DOAC doses based on real-time data. This method aims to reduce major bleeding by administering the medication only when the smartwatch detects an irregular heartbeat, potentially avoiding unnecessary use. Meanwhile, participants in the Continuous DOAC therapy arm will continue their previously prescribed DOAC regimen, following current practice standards. These newer treatments carry a lower risk of causing serious brain bleeding compared to some older drugs. ^{2 3 4 6 7}

Who Is on the Research Team?

Dan Hanley

Principal Investigator

Johns Hopkins University

Rod Passman

Principal Investigator

Northwestern University

Are You a Good Fit for This Trial?

This trial is for adults aged 22-85 with a history of Atrial Fibrillation (AF) and low-to-moderate stroke risk, who can use a smartwatch and smartphone. They must be on DOAC therapy but willing to stop if needed, not at high risk for non-cardioembolic stroke, without severe heart conditions or other health issues that increase bleeding risks.

Inclusion Criteria

I have a history of irregular heartbeats lasting more than 30 seconds.

Willing and able to comply with the protocol, including possession of a smartwatch-compatible smartphone with a cellular service plan, willingness to wear the Apple watch at least 14 hours a day, expected to be within cellular service range at least 80% of the time, willingness and ability to discontinue DOAC, and willingness and ability to provide informed consent

I am currently taking a blood thinner that is not warfarin.

Exclusion Criteria

I am taking aspirin or similar drugs regularly and cannot stop for the study.

My kidney function is severely reduced.

I have atrial flutter that hasn't been treated with ablation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to either AFSW-guided, time-delimited DOAC therapy or continuous DOAC therapy

60 months

Regular monitoring through the REACT-AF app

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AFSW Guided DOAC
• Continuous DOAC therapy

Trial Overview

REACT-AF compares continuous Direct Oral Anticoagulation (DOAC) with time-limited DOAC guided by an AF-sensing Smart Watch (AFSW). Participants are randomly assigned to either continue their regular DOAC treatment or switch to using the smartwatch-guided method for one month.

How Is the Trial Designed?

Group I: AFSW Guided DOAC Experimental Treatment 1 Intervention

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.

Group II: Continuous DOAC therapy Active Control 1 Intervention

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.

AFSW Guided DOAC is already approved in European Union, United States for the following indications:

Approved in European Union as Eliquis for:

• Prevention of stroke and systemic embolism in non-valvular atrial fibrillation
• Prevention of deep vein thrombosis and pulmonary embolism after hip or knee replacement surgery
• Treatment of deep vein thrombosis and pulmonary embolism

Approved in United States as Eliquis for:

• Prevention of stroke and systemic embolism in non-valvular atrial fibrillation
• Prevention of deep vein thrombosis and pulmonary embolism after hip or knee replacement surgery
• Treatment of deep vein thrombosis and pulmonary embolism

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Northwestern University

Collaborator

Trials

1,674

Recruited

989,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

A survey of 620 Italian physicians revealed strong consensus on the pharmacological and clinical implications of using lower doses of direct oral anticoagulants (DOACs) like dabigatran, apixaban, edoxaban, and rivaroxaban in patients with nonvalvular atrial fibrillation, particularly regarding dose adjustments for moderate kidney insufficiency.

Despite the general agreement on lower dose usage, there remains some uncertainty about the dosing and plasma concentration relationship for dabigatran, indicating a need for ongoing education among healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How lower doses of direct oral anticoagulants are interpreted in clinical practice: a national survey of the Italian Atherosclerosis, Thrombosis and Vascular Biology (ATVB) Study Group. Rubboli, A., Fresco, C., Paciaroni, M., et al.[2023]

In a study involving 169 patients undergoing atrial fibrillation ablation, edoxaban showed a low risk of ischemic strokes and bleeding events within the first 30 days post-procedure, suggesting it is a safe option for patients on direct oral anticoagulants during ablation.

Most ablations (81%) were performed after a significant interruption of the anticoagulant (median 18 days), and no ischemic events or deaths occurred in patients with ≤10 days of drug interruption, indicating that careful management of anticoagulation can enhance safety during AF ablation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First experience with edoxaban and atrial fibrillation ablation - Insights from the ENGAGE AF-TIMI 48 trial. Steffel, J., Ruff, CT., Hamershock, RA., et al.[2018]

In a study of 713 patients aged 80 and older with atrial fibrillation, both reduced and full doses of direct-acting oral anticoagulants (DOACs) effectively reduced the risk of stroke and systemic embolization, with low rates of central nervous system bleeding regardless of the dose.

However, patients on reduced doses experienced higher rates of non-central nervous system bleeding and mortality, which were linked to their worse baseline health characteristics, indicating the need for further research into the causes of these complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective Comparison of Patients ≥ 80 Years With Atrial Fibrillation Prescribed Either an FDA-Approved Reduced or Full Dose Direct-Acting Oral Anticoagulant. Taoutel, R., Ezekowitz, MD., Chaudhry, UA., et al.[2022]

Direct-acting oral anticoagulants (DOACs) like dabigatran, rivaroxaban, apixaban, and edoxaban are effective alternatives to traditional vitamin K antagonists for preventing strokes in patients with atrial fibrillation, showing comparable efficacy and a lower risk of intracranial bleeding.

DOACs are particularly beneficial for older adults due to their strategic dosing and lack of need for regular blood testing, but they are not recommended for patients with mechanical heart valves or severe mitral stenosis, and their safety in patients with liver disease and those on renal replacement therapy is still uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Direct-Acting Oral Anticoagulants in Atrial Fibrillation: What's New in the Literature. Ferrari, F., da Silveira, AD., Martins, VM., et al.[2023]

A study involving 91 patients and 184 samples found that apixaban and rivaroxaban levels in plasma can be effectively monitored using conventional tests like PT and dRVVT, indicating their reliability for assessing anticoagulant effects.

The established on-therapy ranges for both apixaban and rivaroxaban provide valuable benchmarks for clinicians to ensure effective and safe dosing in patients undergoing treatment with these direct oral anticoagulants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of global laboratory methods and establishing on-therapy ranges for monitoring apixaban and rivaroxaban: Experience at a single institution. Park, SH., Seo, YH., Park, PW., et al.[2021]

In a study of 4734 hospitalized patients with atrial fibrillation (AF), 60.5% were eligible for apixaban trials, 52.6% for dabigatran, and 35.8% for rivaroxaban, indicating that apixaban and dabigatran trials are more representative of this patient population.

About 33.4% of patients were eligible for all three DOAC trials, suggesting that the findings from these trials can be applied to a significant portion of hospitalized AF patients, particularly for apixaban and dabigatran.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The representativeness of direct oral anticoagulant clinical trials to hospitalized patients with atrial fibrillation. Fanning, L., Ilomäki, J., Bell, JS., et al.[2018]

In a study of 3385 atrial fibrillation patients undergoing catheter ablation, direct oral anticoagulants (DOACs) like rivaroxaban and dabigatran showed similar effectiveness and safety compared to warfarin, with no significant differences in thromboembolic and major bleeding incidents.

However, the risk of non-major bleeding was found to be higher with rivaroxaban, particularly at both standard and low doses, compared to warfarin and low-dose dabigatran.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety of DOACs in Atrial Fibrillation Patients Undergoing Catheter Ablation: Results from the China Atrial Fibrillation (China-AF) Registry. Dong, Z., Hou, X., Du, X., et al.[2022]

In a study of 160 patients undergoing radial coronary angiography, uninterrupted treatment with direct-acting oral anticoagulants (DOACs) like apixaban, rivaroxaban, or dabigatran did not increase the risk of bleeding complications compared to a control group.

The study found no significant differences in complications such as large hematomas or thrombotic events, suggesting that continuing DOACs during the procedure is safe and effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of radial coronary angiography with uninterrupted direct-acting oral anticoagulant treatment. Kemaloğlu Öz, T., Gürol, T., Sarıgül, NU., et al.[2019]

In a study of 21,038 atrial fibrillation patients in Germany, edoxaban was found to be more effective than other oral anticoagulants, showing significantly lower risks of ischemic stroke or systemic embolism compared to apixaban, dabigatran, rivaroxaban, and vitamin K antagonists.

Edoxaban also exhibited a favorable safety profile, with lower risks of major bleeding compared to rivaroxaban and vitamin K antagonists, while showing similar bleeding risks to apixaban and dabigatran.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of clinical outcomes of edoxaban versus apixaban, dabigatran, rivaroxaban, and vitamin K antagonists in patients with atrial fibrillation in Germany: A real-world cohort study. Marston, XL., Wang, R., Yeh, YC., et al.[2022]

A network meta-analysis of 21 randomized clinical trials involving 96,017 patients with nonvalvular atrial fibrillation showed that various antiembolic therapies, including novel oral anticoagulants (NOACs) and the Watchman device, significantly reduced the risk of stroke and systemic embolism compared to placebo.

All antiembolic interventions also demonstrated a reduction in all-cause mortality, with NOACs like apixaban, dabigatran, and edoxaban showing lower mortality rates compared to vitamin K antagonists (VKAs).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Effectiveness of Interventions for Stroke Prevention in Atrial Fibrillation: A Network Meta-Analysis. Tereshchenko, LG., Henrikson, CA., Cigarroa, J., et al.[2023]

Healthcare professionals (HCPs) and patients demonstrated satisfactory knowledge of bleeding risks associated with apixaban, with 96.1% of HCPs recognizing symptoms that require immediate attention and 71.2% of patients identifying abnormal bleeding as a significant side effect.

The study found that a significant majority of HCPs (97.8%) who received the Prescriber Guide utilized it in patient discussions, and 90.9% of patients who received the Patient Alert Card read it at least once, indicating effective distribution and utilization of these educational materials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the Effectiveness of Apixaban Additional Risk Minimisation Measures Using Surveys in Europe. Mayall, S., Kahlon, R., Al-Dakkak, I., et al.[2021]

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Smartwatch-Guided DOAC Therapy for Atrial Fibrillation

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