SENIOR: Stroke Prevention in the Elderly by Patent Foramen Ovale closuRe vs Anticoagulation (SENIOR)

March 18, 2026 updated by: I-Hui Lee, Taichung Veterans General Hospital

Patent Foramen Ovale-Related Stroke Management and Outcome: Age-dependent Risk Prediction and Atrial Cardiopathy Study (SENIOR Study)

Patent foramen ovale (PFO) is an important mechanism of embolic stroke of undetermined source (ESUS). Current guidelines recommend PFO closure for high-risk PFO in patients younger than 60 years, and a recent retrospective cohort study from Taichung Veterans General Hospital has shown that closure is effective and safe in older adults; however, the optimal treatment strategy for those >60 years and direct head-to-head comparisons of PFO closure versus direct oral anticoagulants (DOACs) remain insufficient. Robust evidence from a multicenter study combining prospective and retrospective cohorts is warranted.

The SENIOR study is a multicenter observational cohort registry with a combined retrospective and prospective design. The prospective period is from September 15, 2025 to December 31, 2031, and the retrospective period covers January 1, 2013 to September 1, 2025; target sample sizes are 400 (prospective) and 500 (retrospective). We will enroll adults with ESUS and PFO; the prospective arm will focus on patients aged >60 years with PFO related stroke. Treatments will be assigned as PFO closure, standard-dose DOAC, or antiplatelet agents (if DOAC intolerance) by local principal investigator. The primary outcome is recurrent ischemic stroke or transient ischemic attack. Secondary outcomes include 6-month functional outcome, all stroke, and serial comparison of atrial cardiopathy changes. Safety endpoints include peri-procedural adverse events (including newly-onset atrial fibrillation), hemorrhagic stroke, and all caused mortality. Clinical presentation, imaging, cardiac testing, biomarker, and genetic data will be collected for stratified and multivariable analyses.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Patent foramen ovale-related stroke management and outcome: age-dependent risk prediction and atrial cardiopathy study (SENIOR study) is a multicenter, hybrid retrospective-prospective observational registry designed to address a critical therapeutic gap in the management of embolic stroke of undetermined source (ESUS) associated with patent foramen ovale (PFO), particularly in patients older than 60 years. While randomized controlled trials and contemporary international guidelines support transcatheter PFO closure in carefully selected patients younger than 60 years with high-risk anatomical features, robust evidence remains lacking for older adults, despite the fact that the majority of stroke patients worldwide are now above this age threshold and emerging data suggest that recurrence risk in medically treated elderly patients with PFO may be even higher than in younger cohorts. Furthermore, although anticoagulation-especially with direct oral anticoagulants (DOACs)-has been hypothesized to offer protection comparable to closure in preventing paradoxical embolism, prior trials included very few DOAC-treated patients and did not provide adequately powered head-to-head comparisons between closure and modern anticoagulation strategies. Building upon preliminary real-world data from Taichung Veterans General Hospital demonstrating substantial recurrence reduction with PFO closure in older adults but limited representation of DOAC therapy, the SENIOR registry aims to generate generalizable, decision-relevant evidence by enrolling approximately 900 patients across participating centers, combining retrospective cases (2013-2025) with prospective enrollment (2025-2031). Eligible participants are adults aged 18-90 years with ESUS and confirmed PFO after standardized etiologic work-up, with the prospective arm emphasizing patients ≥60 years who demonstrate high-risk PFO features defined by transcranial Doppler or transesophageal echocardiographic microbubble criteria, atrial septal aneurysm, or long-tunnel anatomy. Treatment allocation is determined through shared decision-making as part of routine care and may include transcatheter PFO closure, standard-dose DOAC therapy, or antiplatelet therapy when anticoagulation is contraindicated, with detailed documentation of clinical rationale to enable rigorous risk adjustment. The primary endpoint is recurrent ischemic stroke or transient ischemic attack, and secondary outcomes include overall stroke events, functional status at one year, safety endpoints such as new-onset atrial fibrillation and major bleeding, and all-cause mortality. In addition to comparative effectiveness analysis using time-to-event modeling and multivariable adjustment, the study incorporates a mechanistic cardiac physiological substudy that longitudinally characterizes atrial cardiopathy and left atrial remodeling through echocardiographic strain, volumetric assessment, and, in closure cases, direct catheter-based left atrial pressure waveform recording to estimate compliance and explore the interaction between structural atrial substrate and paradoxical embolism. By integrating anatomical risk stratification (RoPE and PASCAL classification), age-dependent risk prediction modeling, contemporary antithrombotic strategies, and mechanistic atrial physiology, the SENIOR study seeks to clarify whether advanced age modifies the balance between device-based and pharmacologic stroke prevention, to refine individualized treatment selection for older patients with PFO-related stroke, and to provide the multicenter real-world evidence necessary to inform future randomized trials and guideline evolution.

Study Aims

This is a multicenter, observational cohort study that includes both retrospective and prospective enrollment of patients with patent foramen ovale (PFO)-related stroke. The study aims are:

  1. To optimize an age-inclusive risk prediction system for the causal attribution of PFO-related stroke across all age.
  2. To compare the effectiveness and safety of transcatheter PFO closure versus medical therapy alone (direct oral anticoagulants [DOAC] or antiplatelet agents if protocol-defined DOAC ineligibility) for prevention of recurrent stroke among patients aged ≥60 years with high-risk PFO.
  3. To investigate the role of atrial cardiopathy (AC) in PFO-related stroke, and to further analyze changes in cardiac physiological parameters-such as left atrial (LA) compliance and LA strain-before and after PFO closure and medical therapy alone (optional nested substudy).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
400

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Taiwan
      • Taichung, Taiwan, 40705
        • Recruiting
        • Taichung Veterans General Hospital
        • Contact:
      • Taipei, Taiwan, 100
        • Recruiting
        • National Taiwan University Hospital
        • Contact:
          • Sung-Chun Tang, MD, PhD
      • Taipei, Taiwan, 100
        • Recruiting
        • Taipei Veterans General Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

N/A

Sampling Method

Probability Sample

Study Population

Patients with recent embolic stroke of undetermined source and patent foramen ovale (PFO)

Description

Inclusion Criteria:

  • Patient or his/her legal representative signs a written informed consent
  • Participants who have diagnosed as PFO related stroke
  • For patient aged 18-59: patient with high risk PFO feature or RoPE score ≥ 7
  • For patient aged 60-90: patient with high risk PFO feature or RoPE score ≥ 4, must include cortical infarct

Exclusion Criteria:

  • Follow-up less than 6 months
  • Extracardiac right-to-left shunt
  • Known stroke mechanism was diagnosed

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Non-elderly, medication
Patient with age < 60 year-old, received standard dose DOAC or antiplatelet if protocol-defined DOAC ineligibility
Drug: Medication

Standard dose direct oral anticoagulant (DOAC) or Antiplatelet if protocol-defined DOAC ineligibility

  1. Unavoidable and non-substitutable severe drug interaction
  2. Newly onset on-label contraindication
  3. Patient refusal of DOAC
Non-elderly, PFO closure
Patient with age < 60 year-old, received PFO closure plus antiplatelet
Device: PFO closure
Transcatheter PFO closure by Amplatzer PFO occluder plus long-term antiplatelet (dual antiplatelet for at least 3 month and life-long single antiplatelet )
Other Names:
  • closure
Elderly, medication
Patient with age ≥ 60 year-old, received standard dose DOAC or antiplatelet if protocol-defined DOAC ineligibility
Drug: Medication

Standard dose direct oral anticoagulant (DOAC) or Antiplatelet if protocol-defined DOAC ineligibility

  1. Unavoidable and non-substitutable severe drug interaction
  2. Newly onset on-label contraindication
  3. Patient refusal of DOAC
Elderly, PFO closure
Patient with age ≥ 60 year-old, received PFO closure plus antiplatelet
Device: PFO closure
Transcatheter PFO closure by Amplatzer PFO occluder plus long-term antiplatelet (dual antiplatelet for at least 3 month and life-long single antiplatelet )
Other Names:
  • closure

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Recurrent acute ischemic stroke (AIS) or transient ischemic attack (TIA)
Time Frame: 3 year follow-up, at least > 6 months, event-driven
AIS: Diagnosed by Neurologist by standard pathway TIA: Hemiplegia, lasting for > 10 minutes and documented by Neurologist
3 year follow-up, at least > 6 months, event-driven

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
All strokes and all-cause mortality
Time Frame: 3 year follow-up, at least > 6 months, event-driven
TIA, ischemic and hemorrhagic stroke
3 year follow-up, at least > 6 months, event-driven
Functional outcome
Time Frame: 6 months
modified Rankin scale (mRS) at 6th month after treatment
6 months
Atrial cardiopathy (optional)
Time Frame: 12 months
changes of LA strain (LA global longitudinal strain [GLS]) and LA volume between baseline and 6~12 months after treatment
12 months
Safety outcome
Time Frame: 3 year follow-up, at least > 6 months, event-driven
Peri-procedural adverse events, rocedure related AF (newly-onset AF within 45 days after closure), newly-onset AF (beyond 45 days after closure) in follow-up time, major bleeding, all-cause mortality
3 year follow-up, at least > 6 months, event-driven

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Taichung Veterans General Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Taiwan University Hospital
Taipei Veterans General Hospital, Taiwan

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: I-Hui Lee, MD, PhD, Taipei Veterans General Hospital, Taiwan
  • Study Director: Chi-Sheng Wang, MD, Taichung Veterans General Hospital
  • Study Director: Sung-Chun Tang, MD, PhD, National Taiwan University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 16, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2031

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2031

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 13, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 13, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 18, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 23, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 18, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SENIOR study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Study protocol and informed consent form are available on reasonable request from the principal investigator, I-Hui Lee.

Proposals should be directed to ihui_lee@hotmail.com. To gain access, data requestors will need to sign a data access agreement.

IPD Sharing Time Frame

following paper publication without end date

IPD Sharing Access Criteria

on reasonable request from the principal investigator

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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