Unipolar Voltage-Guided Substrate Modification Plus Pulsed Field Ablation Pulmonary Vein Isolation Versus Pulmonary Vein Isolation Alone in Persistent Atrial Fibrillation (UNI-PFA)

November 3, 2026 updated by: China National Center for Cardiovascular Diseases

Unipolar Voltage-Guided Individualized Substrate Modification Combined With Pulsed Field Ablation-Based Pulmonary Vein Isolation Versus Pulmonary Vein Isolation Alone in Persistent Atrial Fibrillation: A Multicenter, Randomized, Open-Label, Superiority Trial

UNI-PFA is a multicenter, randomized, open-label, superiority trial evaluating whether adding unipolar voltage-guided individualized substrate modification to pulsed field ablation (PFA)-based pulmonary vein isolation (PVI) improves outcomes in patients with persistent atrial fibrillation and a left atrial low-voltage area (LVA) burden of at least 10% of the post-PVI left atrial surface area. Participants are randomized 1:1 to PFA-PVI plus individualized substrate modification (homogenization, box isolation, linear ablation, or a combination) or PFA-PVI alone. The primary endpoint is treatment success at 12 months, defined as freedom from documented atrial fibrillation, atrial tachycardia, or atrial flutter lasting more than 30 seconds after a 90-day blanking period while off class I/III antiarrhythmic drugs. Follow-up includes 14-day continuous ECG patch monitoring at 3, 6, and 12 months, symptom-triggered single-lead ECG, and quality-of-life assessments.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet 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

Background: Pulmonary vein isolation (PVI) is the cornerstone of catheter ablation for atrial fibrillation, but outcomes in persistent atrial fibrillation remain suboptimal, with approximately 50% freedom from recurrence in unselected patients. Left atrial low-voltage areas (LVAs) are an electrical surrogate for atrial fibrosis and predict recurrence after PVI. Unipolar voltage mapping may detect intramural or epicardial fibrosis that bipolar mapping misses. Pulsed field ablation (PFA) provides preferential myocardial ablation with a favorable safety profile. Whether adding unipolar voltage-guided individualized substrate modification to PFA-PVI improves outcomes in patients with a substantial LVA burden is unknown.

Design: UNI-PFA is a multicenter, randomized, open-label, superiority trial. Approximately 294 participants with persistent or long-standing persistent atrial fibrillation and a unipolar LVA burden of at least 10% of the post-PVI left atrial surface area (excluding the pulmonary vein antra, left atrial appendage, and fossa ovalis) will be randomized 1:1. Randomization is stratified by sex and LVA proportion category (10-20%, 20-30%, and >30%). The experimental arm receives PFA-PVI plus individualized substrate modification selected according to LVA location (homogenization, box isolation, linear ablation, or a combination); the active comparator arm receives PFA-PVI alone. All participants receive 14-day continuous ECG patch monitoring at 3, 6, and 12 months, symptom-triggered single-lead ECG, and unscheduled ECG/Holter/telemetry when clinically indicated.

Endpoints: The primary endpoint is treatment success at 12 months, defined as freedom from documented atrial fibrillation, atrial tachycardia, or atrial flutter lasting more than 30 seconds after a 90-day blanking period while off class I/III antiarrhythmic drugs, allowing up to one repeat ablation within 6 months of the index procedure. Patients who remain on class I/III antiarrhythmic drugs at 12 months are counted as treatment failures. Twelve prespecified secondary endpoints include arrhythmia-free survival, quality of life (AFEQT), arrhythmia burden, repeat ablation, procedure duration, and fluoroscopy time. Sixteen prespecified safety endpoints are adjudicated by an independent, blinded clinical events committee.

Eligibility: Adults aged 18 years or older with symptomatic persistent or long-standing persistent atrial fibrillation, suitable for catheter ablation, who have tried at least one class I/III antiarrhythmic drug or are unwilling to do so, and who meet the intraoperative unipolar LVA criterion. Key exclusions include left atrial diameter >55 mm, recent acute coronary syndrome or coronary artery bypass grafting, severe valvular disease, prior atrial fibrillation ablation or left atrial surgery, NYHA class IV heart failure, contraindication to oral anticoagulation, dialysis-dependent renal failure, and pregnancy.

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.
Interventional

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.
294

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

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.
  • Name: Ligang Ding, MD, PhD
  • Phone Number: +8601088233162
  • Email: dlgang@163.com

Study Locations

  • China
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100037
        • Fuwai Hospital, Chinese Academy of Medical Sciences
        • Contact:
          • Ligang Ding, MD, PhD
          • Phone Number: +8601088233162
          • Email: dlgang@163.com
        • Principal Investigator:
          • Ligang Ding, MD, PhD

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. ECG-documented persistent or long-standing persistent atrial fibrillation (ESC definition).
  2. Symptoms (palpitations, dyspnea, fatigue, etc.) attributable to atrial fibrillation.
  3. Suitable for catheter ablation.
  4. At least one class I/III antiarrhythmic drug has been tried, or the patient is unwilling to try.
  5. Age 18 years or older.
  6. Intraoperative left atrial voltage mapping demonstrating a unipolar low-voltage area (cutoff 2.5 mV) of at least 10% of the post-PVI left atrial surface area (excluding the pulmonary vein antra, left atrial appendage, and fossa ovalis).

Exclusion Criteria:

  1. Left atrial diameter >55 mm on echocardiography.
  2. Acute coronary syndrome or coronary artery bypass grafting within 12 weeks.
  3. Severe aortic or mitral valve disease (ESC definition).
  4. Congenital heart disease.
  5. Prior surgical or percutaneous atrial fibrillation ablation, or atrioventricular node ablation.
  6. Prior left atrial surgery.
  7. Comorbidity with expected survival <1 year.
  8. NYHA class IV heart failure symptoms.
  9. Contraindication to oral anticoagulation.
  10. Dialysis-dependent renal failure.
  11. Atrial fibrillation due to reversible causes.
  12. Pregnancy or women of childbearing potential not using contraception.
  13. History of poor treatment adherence.
  14. Unable or unwilling to provide informed consent.

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

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
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.
Experimental: PFA-PVI Plus Individualized Substrate Modification

Pulsed field ablation (PFA)-based pulmonary vein isolation plus unipolar voltage-guided individualized substrate modification. Substrate modification is selected according to low-voltage area location and may include homogenization, box isolation, linear ablation, or a combination.
Device: VARIPULSE Pulsed Field Ablation System

Pulsed field ablation catheter and generator used to perform pulmonary vein isolation in both study arms.

Procedure: Pulmonary Vein Isolation

Pulsed field ablation-based pulmonary vein antral isolation with confirmation of entrance and exit block in all pulmonary veins; performed in both arms.

Procedure: Individualized Substrate Modification

Unipolar voltage-guided individualized substrate modification selected according to low-voltage area location, including homogenization, box isolation, linear ablation, or a combination. Performed in the experimental arm only.
Active Comparator: PFA-PVI Alone

Pulsed field ablation (PFA)-based pulmonary vein isolation alone, without substrate or prophylactic ablation.
Device: VARIPULSE Pulsed Field Ablation System

Pulsed field ablation catheter and generator used to perform pulmonary vein isolation in both study arms.

Procedure: Pulmonary Vein Isolation

Pulsed field ablation-based pulmonary vein antral isolation with confirmation of entrance and exit block in all pulmonary veins; performed in both arms.

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
Treatment Success at 12 Months After the Index Ablation Procedure
Time Frame: 12 months after the index ablation procedure

Freedom from documented atrial fibrillation, atrial tachycardia, or atrial flutter lasting more than 30 seconds after a 90-day blanking period while off class I/III antiarrhythmic drugs, allowing up to one repeat ablation within 6 months of the index procedure (1-2 procedures total). Patients who remain on class I/III antiarrhythmic drugs at 12 months are counted as treatment failures; missing primary outcome data are counted as treatment failures.
12 months after the index ablation procedure

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
Time Frame
Time to First Recurrence After a Single Procedure Off Antiarrhythmic Drugs
Time Frame: 12 months after the index procedure
12 months after the index procedure
Change in AFEQT Quality-of-Life Score From Baseline to 12 Months
Time Frame: Baseline and 12 months
Baseline and 12 months
Incidence of Prespecified Procedure-Related Complications
Time Frame: 90 days after ablation; all-cause mortality at 12 months
90 days after ablation; all-cause mortality at 12 months
Freedom From Atrial Arrhythmia at 12 Months After a Single Procedure Off Antiarrhythmic Drugs
Time Frame: 12 months
12 months
Freedom From Atrial Arrhythmia at 12 Months After a Single Procedure With or Without Antiarrhythmic Drugs
Time Frame: 12 months
12 months
Freedom From Atrial Arrhythmia at 12 Months After 1-2 Procedures With or Without Antiarrhythmic Drugs
Time Frame: 12 months
12 months
Freedom From Atrial Fibrillation at 12 Months After 1-2 Procedures Off Antiarrhythmic Drugs
Time Frame: 12 months
12 months
Atrial Arrhythmia Burden at 3, 6, and 12 Months
Time Frame: 14-day period before each follow-up visit
14-day period before each follow-up visit
Time to First Recurrence After Any Number of Procedures
Time Frame: 12 months
12 months
Number of Repeat Ablations Within 12 Months
Time Frame: 12 months after the index procedure
12 months after the index procedure
Procedure Duration
Time Frame: Index procedure
Index procedure
Total Fluoroscopy Time
Time Frame: Index procedure
Index procedure

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.
China National Center for Cardiovascular Diseases

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.
The Second Hospital of Hebei Medical University
Guangdong Provincial People's Hospital
Affiliated Hospital of Hebei University
The Second Affiliated Hospital of Chongqing Medical University
Second Affiliated Hospital of Xi'an Jiaotong University
Sir Run Run Shaw Hospital
The University of Hong Kong-Shenzhen Hospital
Shanxi Cardiovascular Hospital

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: Ligang Ding, MD, PhD, Chinese Academy of Medical Sciences, Fuwai 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 (Estimated)

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.
November 1, 2026

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 1, 2028

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 1, 2029

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).
November 3, 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.
November 3, 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.
November 9, 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.
November 9, 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.
November 3, 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.
October 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.
  • UNI-PFA-2026-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual participant data will not be shared. Aggregate study results will be published and presented. The informed consent and institutional data-governance approvals do not permit public deposition of individual participant data.

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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