Posterior Wall Substrate Modification Using Irreversible Electroporation for Paroxysmal Atrial Fibrillation ((SMILE-AF))

May 12, 2026 updated by: Jorge Romero

Posterior Wall Substrate Modification Using Irreversible Electroporation for the Treatment of Paroxysmal Atrial Fibrillation

The purpose of this study is to compare the efficacy and safety between pulmonary vein isolation (PVI) alone versus PVI with left atrial (LA) posterior wall isolation (PWI) using pulsed-field ablation (PFA) in the treatment of patients with paroxysmal atrial fibrillation (PAF).

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

This is an investigator-initiated, prospective, randomized, multi-center, Investigational Device Exemption (IDE) study. Subjects undergoing first-time ablation for paroxysmal atrial fibrillation will be randomized to receive either pulmonary vein isolation (PVI) alone or PVI combined with posterior wall isolation (PWI) using pulsed field ablation (PFA) with the FARAWAVE PFA catheter.

Following the index procedure, all participants will enter a 3-month blanking period, during which they will be closely monitored. After this period, anti-arrhythmic drug (AAD) therapy will be discontinued for all patients. Throughout the entire study, patients will be monitored using an implantable loop recorder (ILR) to assess the primary outcome of efficacy.

The study includes a 12-month follow-up period, and the primary objective is to assess and compare the efficacy, defined as an improvement in freedom from all-atrial arrhythmias, and safety, defined as the occurrence of all procedure-related complications.

Study Type

Interventional

Enrollment (Actual)

198

Phase

  • 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 Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35243
        • Grandview Medical Center
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20010
        • MedStar Washington Hospital Center
    • Florida
      • Jacksonville, Florida, United States, 32204
        • St. Vincent's Health System, Inc. d/b/a Ascension St. Vincent's
      • Miami, Florida, United States, 33133
        • HCA Florida Mercy Hospital
    • Idaho
      • Boise, Idaho, United States, 83712
        • St. Luke's Boise Medical Center
    • Maine
      • Portland, Maine, United States, 04102
        • Maine Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Brigham and Women's Hospital
      • Burlington, Massachusetts, United States, 01805
        • Lahey Hospital and Medical Center
    • Michigan
      • Royal Oak, Michigan, United States, 48073
        • Corewell Health William Beaumont Hospital
    • New Jersey
      • Paramus, New Jersey, United States, 07652
        • The Valley Hospital
    • New York
      • Manhasset, New York, United States, 11030
        • North Shore University Hospital, Northwell Health
    • Pennsylvania
      • Doylestown, Pennsylvania, United States, 18901
        • Doylestown Hospital
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
      • Charleston, South Carolina, United States, 29406
        • Trident Medical Center
    • Texas
      • Houston, Texas, United States, 77034
        • Orion Medical
      • San Antonio, Texas, United States, 78229
        • University of Texas Health Science Center at San Antonio
      • San Antonio, Texas, United States, 78229
        • Methodist Hospital-San Antonio
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington Medical Center

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

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Provision of signed and dated informed consent form.
  2. Stated willingness to comply with all study procedures and availability for the duration of the study.
  3. Age 21-90 years.
  4. Symptomatic PAF whether failed AAD or not.
  5. At least one symptomatic episode of PAF lasting <7 days, documented on electrocardiogram (ECG), Holter, ZioPatch, ILR, or smartwatch recording in the year prior to enrollment.
  6. Patients undergoing first time ablation for AF.
  7. Subject has any commercially available implantable loop recorder (ILR) or agrees to have one implanted prior or during the ablation procedure.

Exclusion Criteria:

  1. Persistent atrial fibrillation (PeAF) (> 7 days in duration).
  2. Atrial arrhythmias secondary to electrolyte imbalance, thyroid disease, or other reversible non-cardiac cause.
  3. Previous surgical or catheter ablation of AF.
  4. Previous valve surgery, ventriculotomy, atriotomy, or presence of a mitral mechanical prosthetic or bioprosthetic valve.
  5. Left atrium anteroposterior (LA AP) diameter >55 mm or indexed left atrium (LA) volume >48 ml/m2.
  6. Contraindications to oral or systemic anticoagulation.
  7. Previous thromboembolic event (including ischemic strokes and TIA) within the last 3 months.
  8. Previous myocardial infarction or percutaneous coronary intervention within the past 2 months.
  9. Coronary Artery Bypass Grafting (CABG) surgery within the past 6 months (180 days).
  10. Pregnancy.
  11. History of PV stenosis.
  12. History of severe pulmonary hypertension.
  13. History of diaphragmatic paresis or hemi-paresis.
  14. History of heart transplantation.
  15. History of blood clotting or bleeding abnormalities.
  16. Life expectancy of less than 12 months.
  17. Presence of intracardiac thrombus.
  18. Complex congenital heart disease, including tetralogy of Fallot, ventricular septal defects, Ebstein's anomaly, systemic right ventricle, and transposition of the great arteries.
  19. Intracardiac or vascular abnormalities that preclude adequate catheter introduction or manipulation within the LA.
  20. Pacing dependent patients.
  21. Active malignancy or history of treated malignancy within 12 months of enrollment (other than cutaneous basal cell or squamous cell carcinoma).
  22. Active systemic infection.
  23. Participation in any other AF-related randomized clinical trial.

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: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Pulmonary Vein Isolation (PVI) only
Pulsed field ablation of the pulmonary veins only.
Device: Farapulse PFA, Pulmonary Vein Isolation alone
Ablation of the pulmonary veins for the treatment of Paroxysmal Atrial Fibrillation using pulsed field ablation.
Active Comparator: Pulmonary Vein Isolation and Posterior Wall Isolation ( PVI+PWI)
Pulsed field ablation of the pulmonary veins and the posterior wall of the left atrium.
Device: Farapulse PFA, Pulmonary Vein Isolation and Left atrial Posterior Wall Isolation
Ablation of the pulmonary veins and the left atrium posterior wall for the treatment of Paroxysmal Atrial Fibrillation using pulsed field ablation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Procedural success, defined as freedom from of all documented atrial arrhythmias episodes after the 3-month blanking period.
Time Frame: 12 months

will be assessed by:

  • Occurrence of all atrial arrhythmias after the 3-month blanking period.
  • Any cardioversion for atrial fibrillation (AF), atrial flutter (AFL), or atrial tachycardia (AT) after the 3-month blanking period.
  • Use of any type I or type III antiarrhythmic medication for the treatment of AF, AFL, or AT after the 3-month blanking period, or the use of amiodarone at any time.
  • Re-ablation of AF, AFL, or AT.
12 months
The primary safety endpoint is a composite of acute procedure-related complications and any other major adverse events within the 12 months following the ablation procedure.
Time Frame: 12 Months
All number of acute procedure-related complications will be reported and assessed including: atrio-esophageal fistula, cardiac perforation, pulmonary vein (PV) stenosis, acute kidney injury, phrenic nerve paralysis, thromboembolic events, stroke, or transient ischemic attacks (TIA), and other major adverse events within the 12 months following the ablation procedure: pericarditis cardiac tamponade pericardial effusion, coronary artery spasm, Vascular access complication/major bleeding, local hematoma, ecchymosis left atrium or vascular laceration
12 Months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Freedom from atrial arrhythmias medication
Time Frame: 12 Months
Time and dose of anti arrhythmic medications use will be compared between the two groups.
12 Months
Procedural time
Time Frame: 12 Months
procedural time will be compared among groups.
12 Months
Procedure-related Recurrencies
Time Frame: 12 Months
Rate of PV and PW reconnection in patients undergoing repeat ablation procedures for recurrence of AF.
12 Months
Atrial Fibrillation Effect on Quality-of-life Questionnaire (AFEQT).
Time Frame: 12 Months
It reports scores from 0 to 100. A score of 0 corresponds to complete disability, while a score of 100 describes the highest level of QoL
12 Months
Use of amiodarone
Time Frame: 12 months
Number of patients using amiodarone, and duration of using it will be compared among groups.
12 months
Complications.
Time Frame: 12 Months.
Incidence of acute procedure-related complications and long-term procedure-related complication.
12 Months.
fluoroscopy time.
Time Frame: during 1-2 hours procedure.
fluoroscopy time will be asses between the two groups.
during 1-2 hours procedure.
Pulsed field ablation (PFA) applications during procedure.
Time Frame: During 1-2 hours procedure.
The PFA count will be compared by the two groups.
During 1-2 hours procedure.
first-pass pulmonary vein isolation (PVI).
Time Frame: During 1-2 hours procedure.
the rates of first pass PVI will be compared between the two groups.
During 1-2 hours procedure.

Collaborators and Investigators

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

Sponsor

Jorge Romero

Collaborators

Boston Scientific Corporation
Databean

Investigators

  • Principal Investigator: Jorge E Romero, MD, Massachusetts General Hospital
  • Principal Investigator: William H Sauer, MD, Massachusetts General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

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)

October 8, 2024

Primary Completion (Actual)

November 16, 2025

Study Completion (Actual)

November 16, 2025

Study Registration Dates

First Submitted

April 8, 2024

First Submitted That Met QC Criteria

April 11, 2024

First Posted (Actual)

April 15, 2024

Study Record Updates

Last Update Posted (Actual)

May 15, 2026

Last Update Submitted That Met QC Criteria

May 12, 2026

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024P000883

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.

Yes

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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