Clinical trial NCT06521463: SIMPLAAFY Clinical Trial
Official title: WATCHMAN FLX™ Pro Left Atrial Appendage Closure Device With Alternative Post-Implant Monotherapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Atrial Fibrillation
Stroke
Bleeding
Lead sponsor: Boston Scientific Corporation
Sponsor class: INDUSTRY
First posted: 2024-07-26
Enrollment: 1857
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: 6 months after randomization
measure: 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.
timeFrame: 6 months after randomization
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Birmingham
state: Alabama
city: Birmingham
country: United States
facility: Grandview Medical Center
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Cardiovascular Research Group
state: Arizona
city: Scottsdale
country: United States
facility: HonorHealth Heart Group - Shea
state: Arizona
city: Tucson
country: United States
facility: Tucson Medical Center Healthcare
state: Arizona
city: Jonesboro
country: United States
facility: Arrhythmia Research Group
state: Arkansas
city: Burlingame
country: United States
facility: Mills Peninsula Health Services
state: California
city: Concord
country: United States
facility: John Muir Medical Center
state: California
city: La Jolla
country: United States
facility: Scripps Memorial Hospital
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: Santa Barbara
country: United States
facility: Santa Barbara Cottage Hospital
state: California
city: Thousand Oaks
country: United States
facility: Los Robles Hospital & Medical Center
state: California
city: Ventura
country: United States
facility: Cardiology Associates Medical Group
state: California
city: Lakewood
country: United States
facility: Colorado Heart and Vascular PC
state: Colorado
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: Washington
country: United States
facility: Washington Hospital
state: District of Columbia
city: Jacksonville
country: United States
facility: Baptist Medical Center
state: Florida
city: Miami
country: United States
facility: HCA Florida Mercy Hospital
state: Florida
city: Naples
country: United States
facility: Naples Community Hospital
state: Florida
city: Sarasota
country: United States
facility: Sarasota Memorial Hospital
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Macon
country: United States
facility: Georgia Arrhythmia Consultants
state: Georgia
city: Marietta
country: United States
facility: Wellstar Kennestone Hospital
state: Georgia
city: Savannah
country: United States
facility: Memorial Health University Medical Center
state: Georgia
city: Boise
country: United States
facility: St. Luke's Boise Medical Center
state: Idaho
city: Evanston
country: United States
facility: Evanston Hospital
state: Illinois
city: Naperville
country: United States
facility: Midwest Cardiovascular Institute
state: Illinois
city: Oak Lawn
country: United States
facility: Advocate Christ Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Community Heart and Vascular Hospita
state: Indiana
city: Des Moines
country: United States
facility: Mercy Hospital Medical Center
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas
state: Kansas
city: Lexington
country: United States
facility: Baptist Health Lexington
state: Kentucky
city: Louisville
country: United States
facility: Norton Hospital
state: Kentucky
city: Fall River
country: United States
facility: Charlton Memorial
state: Massachusetts
city: Ann Arbor
country: United States
facility: St. Joseph Mercy Hospital
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Maplewood
country: United States
facility: M Health Fairview St John's Hospital
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Foundation
state: Minnesota
city: Saint Cloud
country: United States
facility: Centracare Heart and Vascular Center
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Tupelo
country: United States
facility: North Mississippi Medical Center
state: Mississippi
city: Kansas City
country: United States
facility: St. Luke's Hospital of Kansas City
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Marlton
country: United States
facility: Virtua Health
state: New Jersey
city: Paramus
country: United States
facility: Valley Hospital
state: New Jersey
city: Albuquerque
country: United States
facility: Lovelace Medical Center
state: New Mexico
city: Buffalo
country: United States
facility: Kaleida Health
state: New York
city: New York
country: United States
facility: New York University Medical Center
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Charlotte
country: United States
facility: Novant Health Presbyterian Medical Center
state: North Carolina
city: Raleigh
country: United States
facility: Rex Hospital
state: North Carolina
city: Raleigh
country: United States
facility: Wake Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Bethesda North Hospital-Hospital
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Portland
country: United States
facility: Legacy Emanuel Hospital & Health Center
state: Oregon
city: Harrisburg
country: United States
facility: Pinnacle Health at Harrisburg Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Trident Medical Center
state: South Carolina
city: Columbia
country: United States
facility: Prisma Health
state: South Carolina
city: Germantown
country: United States
facility: Stern Cardiovascular Foundation
state: Tennessee
city: Nashville
country: United States
facility: St. Thomas Heart
state: Tennessee
city: Austin
country: United States
facility: Texas Cardiac Arrhythmia Research
state: Texas
city: Houston
country: United States
facility: Memorial Hermann Memorial City Medical Center
state: Texas
city: San Antonio
country: United States
facility: Methodist Hospital
state: Texas
city: Tyler
country: United States
facility: Christus Trinity Mother Frances Health System-Hospital
state: Texas
city: Salt Lake City
country: United States
facility: St. Mark's Hospital
state: Utah
city: Norfolk
country: United States
facility: Sentara Norfolk General Hospital
state: Virginia
city: Richmond
country: United States
facility: Chippenham & Johnston-Willis Hospital
state: Virginia
city: Roanoke
country: United States
facility: Carilion Roanoke Memorial Hospital
state: Virginia
city: Bellevue
country: United States
facility: Overlake Hospital Medical Center
state: Washington
city: Morgantown
country: United States
facility: Monongalia General Hospital
state: West Virginia
city: Green Bay
country: United States
facility: Bellin Health
state: Wisconsin
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Vivek Reddy, MD
role: STUDY_CHAIR
affiliation: Los Robles Health System
name: Saibal Kar, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Cleveland Clinic
name: Walid Saliba, MD
role: PRINCIPAL_INVESTIGATOR
References: