The Effectiveness of Patch-Based Screening for Pre-Symptomatic Atrial Fibrillation to Improve Patient Outcome (VALIANT-AF-S)

CSP #2037S - Veterans Affairs Learning Health System Initiative to Assess Novel Screening vs. Usual Care and Treatment With Apixaban vs. Rivaroxaban in Veterans With Atrial Fibrillation (VALIANT-AF-S) Trial

• The goal of the screening trial is to determine whether early screening for atrial fibrillation improves outcomes, including lowering the chance of death, hospitalization for stroke, blood clots, heart failure, heart attack, and severe bleeding reduces the risk of stroke or heart failure.
• Atrial fibrillation is a common heart condition in which one of the heart chambers doesn't follow a normal rhythm. Blood clots can form as a result, and they can travel to the brain and cause strokes, or to other organs.
• Almost everyone with atrial fibrillation is treated with drugs called anticoagulants ("blood thinners") to reduce the risk of stroke. These drugs also increase the risk of bleeding.
• Testing for atrial fibrillation is usually done for patients who have symptoms of an irregular or unusually fast or slow heartbeat, often called "palpitations" or a sensation of the heart pounding or stopping for a short period of time.
• What is not known is whether screening people who do not have symptoms of atrial fibrillation, but who are at above-average risk of getting atrial fibrillation, will reduce death, hospitalization for stroke, blood clots, heart failure more than it increases hospitalization for severe bleeding.
• People who participate in the trial who are selected by chance to receive screening will wear a small heart-rate monitor (Zio Patch) on their skin for 14 days and then return it to the manufacturer. Their doctors will be notified about the results and will make decisions about any treatment to recommend.
• The screening trial is expected to enroll about 24,000 VA patients nationwide and to last 7 years, but each person's active participation in the trial is completed after sending in the Zio Patch. After that, the study team will just collect information from the participant's electronic medical records.

Study Overview

• Status: Not yet recruiting
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Device: Zio XT® Patch

Detailed Description

The study hypothesis is that screening for atrial fibrillation (AF) in participants at risk for AF will be associated with a reduction in adverse cardiovascular outcomes. This trial will enroll 24,060 participants with CHA2DS2-VASc score >=3, aged >=65 years without known AF to be randomized to either receive systematic screening at-home with a Zio Patch monitor or to no screening (usual care). If Zio Patch readings indicate AF or another significant arrhythmia, the provider(s) will be advised to consider a set of evidence-based guidelines, including but not limited to anticoagulation. The primary outcome is time to a composite of several events that are complications of AF or its treatment, all of them assessed remotely via electronic administrative records.

The Primary Objective is to assess the effect of a strategy for screening for pre-symptomatic AF on a composite outcome of complications of AF and its treatment, in a prospective, randomized trial. Secondary Objective is to assess the effectiveness of this strategy on the rate of clinical diagnosis of AF.

Primary Endpoint: composite of 1) hospitalization for stroke; 2) hospitalization for systemic embolism; 3) hospitalization for heart failure; 4) hospitalization for acute coronary syndrome; 5) hospitalization for bleeding; 6) death from any cause.

Secondary Endpoints: diagnosis of AF (ICD-10 codes); individual components of the composite outcome.

24,060 patients age >=65 years at approximately 100 VA Medical Centers throughout the US; representation of every VISN and likely every US state is anticipated. CHA2DS2-VASc score >=3 ensures that participants have cardiovascular risk factors (with age considered such a risk factor) but are not necessarily chronically ill. Those already diagnosed with AF, diagnosed with dementia, or anticoagulated long-term for reasons other than AF will be excluded. The VA population is ~89% male with skewing that increases with age; inclusion of Veterans aged 55-64 years and the fact that female sex contributes 1 point to the CHA2DS2-VASc score should increase enrollment of women. Because of the pragmatic trial design and the fact that AF in Veterans <age 55 years is very uncommon, the study population will be restricted to only those >=55 years with AF. However, the primary outcome analysis will include only those Veterans age 65 years in order to assess outcomes from the EHR and other electronic data sources remotely.

Approximately 100 VA Medical Centers with primary care and outpatient cardiology services will be used. The study will not include sites outside the US.

The trial is planned for 3 years of active enrollment and at least 3 years of remote follow-up of the last enrolled participant, thus 6 years of data collection (3-6 years per patient), with an additional year for the completion of data analysis, 7 years (84 months) total.

Participant duration is less than one month to enroll in the screening trial and complete the Zio Patch screening procedure. After that, clinical management is per the participant's providers, and all data are collected remotely using VA and CMS administrative data.

• Study Type: Interventional
• Enrollment (Estimated): 24060
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mustabeen Ashfaq, MS; Phone Number: (857) 364-6026; Email: mustabeen.ashfaq@va.gov

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304-1207
      • VA Palo Alto Health Care System, Palo Alto, CA
      • Contact: Mustabeen Ashfaq, MS; Phone Number: 857-364-6026; Email: mustabeen.ashfaq@va.gov
      • Study Chair: Paul A. Heidenreich, MD MS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

To be eligible to participate in this study, an individual must meet all of the following criteria:

1. Male or female, age >=65 years
2. CHA2DS2-Vasc score >=3. The score is comprised of age (2 points for 75, 1 point for 65-74), sex (1 point for female), history of stroke, TIA, or systemic embolism (2 points), and history of heart failure, hypertension, vascular disease (including MI, peripheral artery disease, or aortic plaque), or diabetes (1 point each).

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Current use of anticoagulation
2. Diagnosis of AF (from administrative records or per patient during consent)
3. Cardio-thoracic surgery in the prior 3 months
4. Presence of pacemaker, implantable defibrillator, or implanted cardiac monitor
5. Clinically significant allergy to adhesives, as reported by the patient during screening for trial enrollment
6. Planned use of a brain or spinal-cord stimulator, TENS unit, or MRI scan during the period when the Zio Patch will be worn

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Systematic Screening Arm; Participants randomized to be systematically screened will receive at-home screening with a Zio XT Patch monitor.	Device: Zio XT® Patch; For participants randomized to be systematically screened, ambulatory ECG monitoring of up to 14 days will be performed using the Zio XT® Patch (iRhythm Inc, San Francisco, CA). The Zio XT® patch is a small, cutaneous ambulatory ECG recording device that provides cardiac rhythm monitoring for up to 14 consecutive days (significantly longer than the 48 hours of monitoring provided by a typical Holter Monitor). The device is approved by the Food and Drug Administration and is in routine clinical use, including in the VA system.; Other Names: Zio Patch
No Intervention: No Screening Arm; Participants randomized to this arm will receive usual care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospitalization for Stroke	Hospitalization for stroke, as determined by ICD-10 codes associated with hospitalization. The primary outcome is time to the first event of stroke, systemic embolism, heart failure, acute coronary syndrome, or major bleeding, or death from any cause (outcomes 1-6).	3 years, assessed remotely via electronic administrative records
Hospitalization for Systemic Embolism	Hospitalization for systemic embolism, as determined by ICD-10 codes associated with hospitalization. The primary outcome is time to the first event of stroke, systemic embolism, heart failure, acute coronary syndrome, or major bleeding, or death from any cause (outcomes 1-6).	3 years, assessed remotely via electronic administrative records
Hospitalization for Heart Failure	Hospitalization for heart failure, as determined by ICD-10 codes associated with hospitalization. The primary outcome is time to the first event of stroke, systemic embolism, heart failure, acute coronary syndrome, or major bleeding, or death from any cause (outcomes 1-6).	3 years, assessed remotely via electronic administrative records
Hospitalization for Acute Coronary Syndrome	Hospitalization for acute coronary syndrome, as determined by ICD-10 codes associated with hospitalization. The primary outcome is time to the first event of stroke, systemic embolism, heart failure, acute coronary syndrome, or major bleeding, or death from any cause (outcomes 1-6).	3 years, assessed remotely via electronic administrative records
Hospitalization for Major Bleeding	Hospitalization for major bleeding, as determined by ICD-10 codes associated with hospitalization. The primary outcome is time to the first event of stroke, systemic embolism, heart failure, acute coronary syndrome, or major bleeding, or death from any cause (outcomes 1-6).	3 years, assessed remotely via electronic administrative records
All-Cause Mortality	Death of any cause, as determined by VA data on vital status. The primary outcome is time to the first event of stroke, systemic embolism, heart failure, acute coronary syndrome, or major bleeding, or death from any cause (outcomes 1-6).	3 years, assessed remotely via electronic administrative records

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of New Diagnosis of AF	Diagnosis of AF will be determined by use of its ICD code or detection of AF sustained for at least 30 seconds using a Zio Patch or other screening device.	3 years

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Study Chair: Paul A. Heidenreich, MD MS, VA Palo Alto Health Care System, Palo Alto, CA

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): October 1, 2032
• Study Completion (Estimated): October 3, 2033

Study Registration Dates

• First Submitted: April 23, 2025
• First Submitted That Met QC Criteria: April 23, 2025
• First Posted (Actual): May 1, 2025

Study Record Updates

• Last Update Posted (Actual): May 1, 2025
• Last Update Submitted That Met QC Criteria: April 23, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Atrial Fibrillation; Ischemic Stroke
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: 2037S; 2037 (Other Grant/Funding Number: Veterans Affairs Cooperative Studies Program)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No