AzTrials
AzTrials

Atrial Fibrillation Paroxysmal(SMILE-AF)NCT06364215

Posterior Wall Substrate Modification Using Irreversible Electroporation for Paroxysmal Atrial Fibrillation

A study testing Farapulse PFA, Pulmonary Vein Isolation alone and Farapulse PFA, Pulmonary Vein Isolation and Left atrial Posterior Wall Isolation in people with Atrial Fibrillation Paroxysmal, run by Jorge Romero at 18 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

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). Read more about this study

Who is it for?
Ages 21 to 90 years
Conditions the study is for
Atrial Fibrillation Paroxysmal
What is being tested?
Farapulse PFA, Pulmonary Vein Isolation alone and Farapulse PFA, Pulmonary Vein Isolation and Left atrial Posterior Wall Isolation
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
198 participants
Where
18 sitesUnited States
Study dates
8 Oct 2024to 16 Nov 2025
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Provision of signed and dated informed consent form.
  • Stated willingness to comply with all study procedures and availability for the duration of the study.
  • Age 21-90 years.
  • Symptomatic PAF whether failed AAD or not.
  • 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.
  • Patients undergoing first time ablation for AF.
  • Subject has any commercially available implantable loop recorder (ILR) or agrees to have one implanted prior or during the ablation procedure.

Who cannot join

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

Trial locations and contacts

18 sites in 1 country.

18 sites in 1 country

United States18 sites

  • Grandview Medical Center

    Birmingham, Alabama, 35243

  • St. Luke's Boise Medical Center

    Boise, Idaho, 83712

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Lahey Hospital and Medical Center

    Burlington, Massachusetts, 01805

  • Trident Medical Center

    Charleston, South Carolina, 29406

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Doylestown Hospital

    Doylestown, Pennsylvania, 18901

  • Orion Medical

    Houston, Texas, 77034

  • St. Vincent's Health System, Inc. d/b/a Ascension St. Vincent's

    Jacksonville, Florida, 32204

  • North Shore University Hospital, Northwell Health

    Manhasset, New York, 11030

  • HCA Florida Mercy Hospital

    Miami, Florida, 33133

  • The Valley Hospital

    Paramus, New Jersey, 07652

  • Maine Medical Center

    Portland, Maine, 04102

  • Corewell Health William Beaumont Hospital

    Royal Oak, Michigan, 48073

  • Methodist Hospital-San Antonio

    San Antonio, Texas, 78229

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229

  • University of Washington Medical Center

    Seattle, Washington, 98195

  • MedStar Washington Hospital Center

    Washington D.C., District of Columbia, 20010

Other trials in United States

About this study

Official title: 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).

Read the 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.

Being tested
Farapulse PFA, Pulmonary Vein Isolation alone, Farapulse PFA, Pulmonary Vein Isolation and Left atrial Posterior Wall Isolation
Keywords
pulsed field ablation, paroxysmal atrial fibrillation, left atrium posterior wall isolation, pulmonary vein isolation
Medical subject headings
Atrial Fibrillation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Farapulse PFA, Pulmonary Vein Isolation aloneDevice

    Ablation of the pulmonary veins for the treatment of Paroxysmal Atrial Fibrillation using pulsed field ablation.

  • Farapulse PFA, Pulmonary Vein Isolation and Left atrial Posterior Wall IsolationDevice

    Ablation of the pulmonary veins and the left atrium posterior wall for the treatment of Paroxysmal Atrial Fibrillation using pulsed field ablation.

Study groups in NCT06364215
Study groupRoleWhat they receive
Pulmonary Vein Isolation (PVI) onlyActive comparatorPulsed field ablation of the pulmonary veins only.
Receives: Device: Farapulse PFA, Pulmonary Vein Isolation alone
Pulmonary Vein Isolation and Posterior Wall Isolation ( PVI+PWI)Active comparatorPulsed field ablation of the pulmonary veins and the posterior wall of the left atrium.
Receives: Device: Farapulse PFA, Pulmonary Vein Isolation and Left atrial Posterior Wall Isolation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Procedural success, defined as freedom from of all documented atrial arrhythmias episodes after the 3-month blanking period.

    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.

    Measured: 12 months

  2. 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.

    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

    Measured: 12 Months

Secondary outcomes (9)

  1. Freedom from atrial arrhythmias medication

    Time and dose of anti arrhythmic medications use will be compared between the two groups.

    Measured: 12 Months

  2. Procedural time

    procedural time will be compared among groups.

    Measured: 12 Months

  3. Procedure-related Recurrencies

    Rate of PV and PW reconnection in patients undergoing repeat ablation procedures for recurrence of AF.

    Measured: 12 Months

  4. Atrial Fibrillation Effect on Quality-of-life Questionnaire (AFEQT).

    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

    Measured: 12 Months

  5. Use of amiodarone

    Number of patients using amiodarone, and duration of using it will be compared among groups.

    Measured: 12 months

  6. Complications.

    Incidence of acute procedure-related complications and long-term procedure-related complication.

    Measured: 12 Months.

  7. fluoroscopy time.

    fluoroscopy time will be asses between the two groups.

    Measured: during 1-2 hours procedure.

  8. Pulsed field ablation (PFA) applications during procedure.

    The PFA count will be compared by the two groups.

    Measured: During 1-2 hours procedure.

  9. first-pass pulmonary vein isolation (PVI).

    the rates of first pass PVI will be compared between the two groups.

    Measured: During 1-2 hours procedure.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Apr 2024
  2. Study start8 Oct 2024
  3. Primary completion16 Nov 2025
  4. Study completion16 Nov 2025

Why it stopped: Insufficient enrollment related to ILR coverage barriers and the resulting inability to meet timelines with the available funding.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Outcomes assessor
Enrolment
198 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06364215
Sponsor's protocol ID
2024P000883
Acronym
(SMILE-AF)
Status last verified
Nov 2025
First submitted
8 Apr 2024
Last updated
15 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
Yes
Individual data sharing
No

Publications

  • Chugh SS, Havmoeller R, Narayanan K, Singh D, Rienstra M, Benjamin EJ, Gillum RF, Kim YH, McAnulty JH Jr, Zheng ZJ, Forouzanfar MH, Naghavi M, Mensah GA, Ezzati M, Murray CJ. Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study. Circulation. 2014 Feb 25;129(8):837-47. doi: 10.1161/CIRCULATIONAHA.113.005119. Epub 2013 Dec 17.

    PubMed 24345399

  • Rahman F, Kwan GF, Benjamin EJ. Global epidemiology of atrial fibrillation. Nat Rev Cardiol. 2016 Jul 14;13(8):501. doi: 10.1038/nrcardio.2016.114. No abstract available.

    PubMed 27411521

  • Wazni OM, Dandamudi G, Sood N, Hoyt R, Tyler J, Durrani S, Niebauer M, Makati K, Halperin B, Gauri A, Morales G, Shao M, Cerkvenik J, Kaplon RE, Nissen SE; STOP AF First Trial Investigators. Cryoballoon Ablation as Initial Therapy for Atrial Fibrillation. N Engl J Med. 2021 Jan 28;384(4):316-324. doi: 10.1056/NEJMoa2029554. Epub 2020 Nov 16.

    PubMed 33197158

  • Andrade JG, Wells GA, Deyell MW, Bennett M, Essebag V, Champagne J, Roux JF, Yung D, Skanes A, Khaykin Y, Morillo C, Jolly U, Novak P, Lockwood E, Amit G, Angaran P, Sapp J, Wardell S, Lauck S, Macle L, Verma A; EARLY-AF Investigators. Cryoablation or Drug Therapy for Initial Treatment of Atrial Fibrillation. N Engl J Med. 2021 Jan 28;384(4):305-315. doi: 10.1056/NEJMoa2029980. Epub 2020 Nov 16.

    PubMed 33197159

  • Kirchhof P, Camm AJ, Goette A, Brandes A, Eckardt L, Elvan A, Fetsch T, van Gelder IC, Haase D, Haegeli LM, Hamann F, Heidbuchel H, Hindricks G, Kautzner J, Kuck KH, Mont L, Ng GA, Rekosz J, Schoen N, Schotten U, Suling A, Taggeselle J, Themistoclakis S, Vettorazzi E, Vardas P, Wegscheider K, Willems S, Crijns HJGM, Breithardt G; EAST-AFNET 4 Trial Investigators. Early Rhythm-Control Therapy in Patients with Atrial Fibrillation. N Engl J Med. 2020 Oct 1;383(14):1305-1316. doi: 10.1056/NEJMoa2019422. Epub 2020 Aug 29.

    PubMed 32865375

  • Chew DS, Jones KA, Loring Z, Black-Maier E, Noseworthy PA, Exner DV, Packer DL, Grant J, Mark DB, Piccini JP. Diagnosis-to-ablation time predicts recurrent atrial fibrillation and rehospitalization following catheter ablation. Heart Rhythm O2. 2021 Nov 19;3(1):23-31. doi: 10.1016/j.hroo.2021.11.012. eCollection 2022 Feb.

    PubMed 35243432

  • Kuck KH, Brugada J, Furnkranz A, Metzner A, Ouyang F, Chun KR, Elvan A, Arentz T, Bestehorn K, Pocock SJ, Albenque JP, Tondo C; FIRE AND ICE Investigators. Cryoballoon or Radiofrequency Ablation for Paroxysmal Atrial Fibrillation. N Engl J Med. 2016 Jun 9;374(23):2235-45. doi: 10.1056/NEJMoa1602014. Epub 2016 Apr 4.

    PubMed 27042964

  • Packer DL, Mark DB, Robb RA, Monahan KH, Bahnson TD, Poole JE, Noseworthy PA, Rosenberg YD, Jeffries N, Mitchell LB, Flaker GC, Pokushalov E, Romanov A, Bunch TJ, Noelker G, Ardashev A, Revishvili A, Wilber DJ, Cappato R, Kuck KH, Hindricks G, Davies DW, Kowey PR, Naccarelli GV, Reiffel JA, Piccini JP, Silverstein AP, Al-Khalidi HR, Lee KL; CABANA Investigators. Effect of Catheter Ablation vs Antiarrhythmic Drug Therapy on Mortality, Stroke, Bleeding, and Cardiac Arrest Among Patients With Atrial Fibrillation: The CABANA Randomized Clinical Trial. JAMA. 2019 Apr 2;321(13):1261-1274. doi: 10.1001/jama.2019.0693.

    PubMed 30874766

  • Romero J, Gabr M, Alviz I, Briceno D, Diaz JC, Rodriguez D, Patel K, Polanco D, Trivedi C, Mohanty S, Della Rocca D, Lakkireddy D, Natale A, Di Biase L. Focal impulse and rotor modulation guided ablation versus pulmonary vein isolation for atrial fibrillation: A meta-analysis of head-to-head comparative studies. J Cardiovasc Electrophysiol. 2021 Jul;32(7):1822-1832. doi: 10.1111/jce.15036. Epub 2021 May 27.

    PubMed 33844385

  • Atienza F, Almendral J, Jalife J, Zlochiver S, Ploutz-Snyder R, Torrecilla EG, Arenal A, Kalifa J, Fernandez-Aviles F, Berenfeld O. Real-time dominant frequency mapping and ablation of dominant frequency sites in atrial fibrillation with left-to-right frequency gradients predicts long-term maintenance of sinus rhythm. Heart Rhythm. 2009 Jan;6(1):33-40. doi: 10.1016/j.hrthm.2008.10.024. Epub 2008 Oct 22.

    PubMed 19121797

  • Narayan SM, Krummen DE, Shivkumar K, Clopton P, Rappel WJ, Miller JM. Treatment of atrial fibrillation by the ablation of localized sources: CONFIRM (Conventional Ablation for Atrial Fibrillation With or Without Focal Impulse and Rotor Modulation) trial. J Am Coll Cardiol. 2012 Aug 14;60(7):628-36. doi: 10.1016/j.jacc.2012.05.022. Epub 2012 Jul 18.

    PubMed 22818076

  • Kistler PM, Chieng D, Sugumar H, Ling LH, Segan L, Azzopardi S, Al-Kaisey A, Parameswaran R, Anderson RD, Hawson J, Prabhu S, Voskoboinik A, Wong G, Morton JB, Pathik B, McLellan AJ, Lee G, Wong M, Finch S, Pathak RK, Raja DC, Sterns L, Ginks M, Reid CM, Sanders P, Kalman JM. Effect of Catheter Ablation Using Pulmonary Vein Isolation With vs Without Posterior Left Atrial Wall Isolation on Atrial Arrhythmia Recurrence in Patients With Persistent Atrial Fibrillation: The CAPLA Randomized Clinical Trial. JAMA. 2023 Jan 10;329(2):127-135. doi: 10.1001/jama.2022.23722.

    PubMed 36625809

  • Markman TM, Hyman MC, Kumareswaran R, Arkles JS, Santangeli P, Schaller RD, Supple GE, Frankel DS, Riley MP, Lin D, Garcia F, Dixit S, Callans DJ, Marchlinski FE, Nazarian S. Durability of posterior wall isolation after catheter ablation among patients with recurrent atrial fibrillation. Heart Rhythm. 2020 Oct;17(10):1740-1744. doi: 10.1016/j.hrthm.2020.05.005. Epub 2020 May 7.

    PubMed 32389682

  • Kumar P, Bamimore AM, Schwartz JD, Chung EH, Gehi AK, Kiser AC, Hummel JP, Mounsey JP. Challenges and Outcomes of Posterior Wall Isolation for Ablation of Atrial Fibrillation. J Am Heart Assoc. 2016 Sep 23;5(9):e003885. doi: 10.1161/JAHA.116.003885.

    PubMed 27663412

  • Aryana A, Thiemann AM, Pujara DK, Cossette LL, Allen SL, Bowers MR, Gandhavadi M, Heath R, Trivedi AD, O'Neill PG, Ellis ER, d'Avila A. Pulmonary Vein Isolation With and Without Posterior Wall Isolation in Paroxysmal Atrial Fibrillation: IMPPROVE-PAF Trial. JACC Clin Electrophysiol. 2023 May;9(5):628-637. doi: 10.1016/j.jacep.2023.01.014. Epub 2023 Mar 22.

    PubMed 37225309

Questions about this trial

What is this clinical trial studying?

A study testing Farapulse PFA, Pulmonary Vein Isolation alone and Farapulse PFA, Pulmonary Vein Isolation and Left atrial Posterior Wall Isolation in people with Atrial Fibrillation Paroxysmal, run by Jorge Romero at 18 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 15 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study was stopped early (reason given: Insufficient enrollment related to ILR coverage barriers and the resulting inability to meet timelines with the available funding.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Procedural success, defined as freedom from of all documented atrial arrhythmias episodes after the 3-month blanking period. (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06364215, which also lists 48 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in