SIMPLAAFY Clinical Trial (SIMPLAAFY)

WATCHMAN FLX™ Pro Left Atrial Appendage Closure Device With Alternative Post-Implant Monotherapy

The primary objective is to demonstrate the safety and effectiveness of two monotherapy regimens versus dual antiplatelet (DAPT) therapy following post-implant with the WATCHMAN FLX Pro device in a commercial clinical setting.

Study Overview

• Status: Active, not recruiting
• Conditions: Stroke; Atrial Fibrillation; Bleeding
• Intervention / Treatment: Device: WATCHMAN FLX Pro LAAC Device

Detailed Description

This study is a prospective, randomized, open-label, triple-arm, multi-center trial. Subjects will be randomized 1:1:1 to one of the three therapy arms and remain on treatment through the end of study (12 months):

1. Aspirin only
2. Reduced dose non-vitamin K antagonist (VKA) oral anticoagulant (NOAC)
3. DAPT

• Study Type: Interventional
• Enrollment (Actual): 1857
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35243
      • Grandview Medical Center
    • Birmingham, Alabama, United States, 35233
      • University of Alabama Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • Phoenix Cardiovascular Research Group
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth Heart Group - Shea
    • Tucson, Arizona, United States, 85712
      • Tucson Medical Center HealthCare
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • Arrhythmia Research Group
  • California
    • Burlingame, California, United States, 94010
      • Mills Peninsula Health Services
    • Concord, California, United States, 94520
      • John Muir Medical Center
    • La Jolla, California, United States, 92037
      • Scripps Memorial Hospital
    • Loma Linda, California, United States, 92354
      • Loma Linda University Medical Center
    • Los Angeles, California, United States, 90404
      • St. John's Health Center
    • Santa Barbara, California, United States, 93105
      • Santa Barbara Cottage Hospital
    • Thousand Oaks, California, United States, 91360
      • Los Robles Hospital & Medical Center
    • Ventura, California, United States, 93003
      • Cardiology Associates Medical Group
  • Colorado
    • Lakewood, Colorado, United States, 80401
      • Colorado Heart and Vascular PC
    • Loveland, Colorado, United States, 80538
      • Medical Center of the Rockies
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Washington Hospital
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Baptist Medical Center
    • Naples, Florida, United States, 34102
      • Naples Community Hospital
    • Sarasota, Florida, United States, 34239
      • Sarasota Memorial Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
    • Macon, Georgia, United States, 31201
      • Georgia Arrhythmia Consultants
    • Marietta, Georgia, United States, 30060
      • Wellstar Kennestone Hospital
    • Savannah, Georgia, United States, 31405
      • Memorial Health University Medical Center
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Straub Medical Center
  • Idaho
    • Boise, Idaho, United States, 83712
      • St. Luke's Boise Medical Center
    • Coeur d'Alene, Idaho, United States, 83814
      • Kootenai Medical Center
  • Illinois
    • Evanston, Illinois, United States, 60201
      • Evanston Hospital
    • Naperville, Illinois, United States, 60540
      • Midwest Cardiovascular Institute
    • Oak Lawn, Illinois, United States, 60453
      • Advocate Christ Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46250
      • Community Heart and Vascular Hospita
  • Iowa
    • Des Moines, Iowa, United States, 50266
      • Mercy Hospital Medical Center
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Baptist Health Lexington
    • Louisville, Kentucky, United States, 40202
      • Norton Hospital
  • Massachusetts
    • Fall River, Massachusetts, United States, 02720
      • Charlton Memorial
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Memorial Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • St. Joseph Mercy Hospital
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Grand Rapids, Michigan, United States, 49503
      • Corewell Health
  • Minnesota
    • Maplewood, Minnesota, United States, 55109
      • M Health Fairview St John's Hospital
    • Rochester, Minnesota, United States, 55902
      • Mayo Clinic Foundation
    • Saint Cloud, Minnesota, United States, 56303
      • Centracare Heart and Vascular Center
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
    • Tupelo, Mississippi, United States, 38801
      • North Mississippi Medical Center
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • St. Luke's Hospital of Kansas City
    • St Louis, Missouri, United States, 63141
      • St. Luke's Hospital
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital - University Medical Center
    • Marlton, New Jersey, United States, 08053
      • Virtua Health
    • Paramus, New Jersey, United States, 07652
      • Valley Hospital
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Lovelace Medical Center
  • New York
    • Bay Shore, New York, United States, 11706
      • Northwell Health
    • Buffalo, New York, United States, 14203
      • Kaleida Health
    • New York, New York, United States, 10016
      • New York University Medical Center
    • The Bronx, New York, United States, 10467
      • Montefiore Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Novant Health Presbyterian Medical Center
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Medical Center
    • Raleigh, North Carolina, United States, 27610
      • Wake Medical Center
    • Raleigh, North Carolina, United States, 27607
      • Rex Hospital
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Bethesda North Hospital-Hospital
    • Cleveland, Ohio, United States, 44106
      • University Hospitals of Cleveland
    • Columbus, Ohio, United States, 43210
      • Ohio State University Medical Center
  • Oregon
    • Portland, Oregon, United States, 97227
      • Legacy Emanuel Hospital & Health Center
  • Pennsylvania
    • Harrisburg, Pennsylvania, United States, 17101
      • Pinnacle Health at Harrisburg Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Trident Medical Center
    • Columbia, South Carolina, United States, 29203
      • Prisma Health
    • Columbia, South Carolina, United States, 29204
      • MUSC Health Columbia Medical Center Downtown
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Stern Cardiovascular Foundation
    • Nashville, Tennessee, United States, 37203
      • St. Thomas Heart
  • Texas
    • Austin, Texas, United States, 78705
      • Texas Cardiac Arrhythmia Research
    • Houston, Texas, United States, 77024
      • Memorial Hermann Memorial City Medical Center
    • Houston, Texas, United States, 77034
      • Orion Medical
    • San Antonio, Texas, United States, 78229
      • Methodist Hospital
    • Tyler, Texas, United States, 75702
      • Christus Trinity Mother Frances Health System-Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • St. Mark's Hospital
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Sentara Norfolk General Hospital
    • Richmond, Virginia, United States, 23235
      • Chippenham & Johnston-Willis Hospital
    • Roanoke, Virginia, United States, 24014
      • Carilion Roanoke Memorial Hospital
  • Washington
    • Bellevue, Washington, United States, 98004
      • Overlake Hospital Medical Center
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
  • West Virginia
    • Morgantown, West Virginia, United States, 26505
      • Monongalia General Hospital
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54305
      • Bellin Health
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Memorial Lutheran Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subject is of legal age to participate in the study per the laws of their respective geography.
• Subject is an acceptable candidate for a WATCHMAN FLX Pro device per the approved Instructions for Use.
• Subject is deemed to be suitable for all protocol defined drug regimens in the control and both test arms.
• The subject or legal representative is able to understand and willing to provide written informed consent to participate in the trial.
• The subject is able and willing to return for required follow-up visits and examinations.

Exclusion Criteria:

• Subject's device implant procedure was aborted (i.e., failed implant).
• Subject has a device margin residual leak > 0mm at time of implant.
• Occurrence of complications (major bleeding, systemic embolism, stroke, pericardial effusion requiring intervention) during the implant procedure, post-procedure, or prior to randomization.
• Subject has a contraindication to one of the three protocol defined drug regimens.
• Subject requires long-term anticoagulation therapy for reason other than AF-related stroke risk reduction or requires chronic P2Y12 inhibitor therapy.
• Subject has known history of severe liver disease including cirrhosis with a Child-Pugh classification C or D.
• Subject with known hypercoagulability disorder, mechanical heart valve, rheumatic heart disease, or recurrent deep vein thrombosis.
• Subject has intracardiac thrombus, LAA sludge, or dense spontaneous echo contrast (SEC) observed during pre-implant imaging.
• Subject has Modified Rankin Score of ≥ 3 at baseline.
• Subject has left ventricular ejection fraction (LVEF) < 30%.
• Subject with known amyloid cardiomyopathy.
• Platelet count ≤ 100,000 x 109/L.
• Subject has an estimated glomerular filtration rate (eGFR) < 30 ml/min (chronic kidney disease stage IV or V) or is on dialysis.
• Subject has a stroke (of any cause, whether ischemic or hemorrhagic) within 30 days prior to implant or prior to randomization.
• Subject has a documented myocardial infarction (MI) as either a non-ST elevation MI (NSTEMI) or as an ST-elevation MI (STEMI), with or without intervention, within 30 days prior to implant or prior to randomization.
• Subject had or is planning to have any cardiac or non-cardiac intervention or surgical procedure within 30 days prior to or 6-months after implant (including, but not limited to, cardioversion, percutaneous coronary intervention, cardiac ablation, cataract surgery, etc.).
• Subject has a major bleeding event per International Society on Thrombosis and Haemostasis (ISTH) definitions within the 30 days prior to implant or prior to randomization. Lack of resolution of related clinical sequelae or planned and pending interventions to resolve bleeding/bleeding source are a further exclusion regardless of timing of the bleeding event.
• Subject has an active bleed.
• Subject has a cardiac tumor.
• Subject has signs/symptoms of acute or chronic pericarditis.
• Subject has an active infection.
• There is evidence of tamponade physiology.
• Subject has New York Heart Association Class IV congestive heart failure at the time of implant or prior to randomization.
• Subject is currently enrolled in another investigational study, except if the subject is participating in a mandatory governmental registry, or a purely observational registry with no associated treatment.
• Subject is of childbearing potential and is, or plans to become, pregnant during the time of the study.
• Subject has a documented life expectancy of less than 12 months.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aspirin; Aspirin 81-100 mg, daily post implant for duration of the clinical trial	Device: WATCHMAN FLX Pro LAAC Device; WATCHMAN FLX Pro LAAC Device Implantation; Other Names: WATCHMAN FLX Pro Left Atrial Appendage Closure Device
Experimental: Reduced dose non-vitamin K antagonist (VKA) oral anticoagulant (NOAC); Reduced dose non-vitamin K antagonist (VKA) oral anticoagulant (NOAC) for the first 3 months daily, post implant, followed by aspirin only for the duration of the clinical trial	Device: WATCHMAN FLX Pro LAAC Device; WATCHMAN FLX Pro LAAC Device Implantation; Other Names: WATCHMAN FLX Pro Left Atrial Appendage Closure Device
Active Comparator: DAPT; DAPT (aspirin 81-100 mg + clopidogrel 75 mg), for the first 6-months daily followed by aspirin only for the duration of the clinical trial	Device: WATCHMAN FLX Pro LAAC Device; WATCHMAN FLX Pro LAAC Device Implantation; Other Names: WATCHMAN FLX Pro Left Atrial Appendage Closure Device

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduced dose NOAC Arm Primary Endpoint: Composite rate of all death, all stroke, systemic embolism, and ISTH major bleeding at 6-months after randomization in the reduced dose NOAC arm tested for non-inferiority compared to the DAPT arm	Non Inferiority	6 months after randomization
Aspirin Arm Primary Endpoint: Composite rate of all death, all stroke, systemic embolism, and ISTH major bleeding at 6-months after randomization in the Aspirin arm tested for non-inferiority compared to the DAPT arm.	Non Inferiority	6 months after randomization

Collaborators and Investigators

• Sponsor: Boston Scientific Corporation
• Investigators: Principal Investigator: Walid Saliba, MD, The Cleveland Clinic; Study Chair: Vivek Reddy, MD, Icahn School of Medicine at Mount Sinai; Principal Investigator: Saibal Kar, MD, Los Robles Health System

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: July 22, 2024
• First Submitted That Met QC Criteria: July 22, 2024
• First Posted (Actual): July 26, 2024

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Pathological Conditions, Signs and Symptoms; Stroke; Atrial Fibrillation; Hemorrhage
• Other Study ID Numbers: S2508

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

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