Smartwatch-Guided DOAC Therapy for Atrial Fibrillation

(REACT-AF Trial)

Recruiting at 88 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

Trial Summary

What is the purpose of this trial?

This trial tests whether taking blood-thinning medication continuously or only when a smart watch detects an irregular heartbeat is better for adults with a history of irregular heartbeats and moderate stroke risk.

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 data supports the effectiveness of the drug Apixaban for atrial fibrillation?

Research shows that Apixaban, a direct-acting oral anticoagulant (DOAC), is effective in preventing stroke in patients with atrial fibrillation. It has been found to be as effective as warfarin, a traditional blood thinner, but with a lower risk of causing serious bleeding in the brain. ^{1 2 3 4 5}

Is Apixaban (Eliquis) generally safe for humans?

Apixaban, a direct oral anticoagulant, is generally considered safe for humans and has a lower risk of causing serious bleeding in the brain compared to older treatments like warfarin. However, its safety in people with liver disease or those needing kidney treatment is not well understood. ^{1 4 6 7 8}

What makes the AFSW Guided DOAC therapy unique for atrial fibrillation?

The AFSW Guided DOAC therapy is unique because it uses a smartwatch to guide the administration of direct-acting oral anticoagulants (DOACs) like Apixaban, which helps in preventing strokes in patients with atrial fibrillation. This approach may offer a more personalized and continuous monitoring method compared to traditional DOAC therapy, potentially improving adherence and outcomes. ^{1 3 9 10 11}

Research Team

Rod Passman

Principal Investigator

Northwestern University

Dan Hanley

Principal Investigator

Johns Hopkins University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Findings from Research

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]

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]

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 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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Direct-Acting Oral Anticoagulants in Atrial Fibrillation: What's New in the Literature. [2023]

2. United States 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. [2021]

3. Germany pubmed.ncbi.nlm.nih.gov

The representativeness of direct oral anticoagulant clinical trials to hospitalized patients with atrial fibrillation. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Comparative Effectiveness of Interventions for Stroke Prevention in Atrial Fibrillation: A Network Meta-Analysis. [2023]

5. United States 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. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

First experience with edoxaban and atrial fibrillation ablation - Insights from the ENGAGE AF-TIMI 48 trial. [2018]

7. Netherlands 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. [2022]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Evaluating the Effectiveness of Apixaban Additional Risk Minimisation Measures Using Surveys in Europe. [2021]

9. Ireland 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. [2022]

10. United States 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. [2022]

11. Turkey pubmed.ncbi.nlm.nih.gov

Safety of radial coronary angiography with uninterrupted direct-acting oral anticoagulant treatment. [2019]