Clinical trial NCT05147792: The CONFORM Pivotal Trial
Official title: An Evaluation of the Safety and Effectiveness of the Conformal CLAAS System for Left Atrial Appendage Occlusion
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Atrial Fibrillation
Stroke
Lead sponsor: Conformal Medical, Inc
Sponsor class: INDUSTRY
First posted: 2021-12-07
Enrollment: 1600
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 CLAAS® device will be evaluated for safety and efficacy by establishing its performance is non-inferior to the commercially available WATCHMAN® and Amulet™ left atrial appendage closure devices in patients with non-valvular atrial fibrillation. Patients who are eligible for the trial will be randomized to receive either the CLAAS device or the WATCHMAN or Amulet™ devices and will be followed for 5 years after device implant.


Eligibility criteria: Inclusion Criteria:

1. Male or non-pregnant female aged ≥18 years
2. Documented non-valvular AF (paroxysmal, persistent, or permanent)
3. High risk of stroke or systemic embolism, defined as CHA2DS2-VASc score of ≥ 3
4. Has an appropriate rationale to seek a non-pharmacologic alternative to long-term oral anticoagulation
5. Deemed by the site investigator to be suitable for short term oral anticoagulation therapy but deemed less favorable for long-term oral anticoagulation therapy.
6. Deemed appropriate for LAA closure by the site investigator and a clinician not a part of the procedural team using a shared decision-making process in accordance with standard of care
7. Able to comply with the protocol-specified medication regimen and follow-up evaluations
8. The subject (or legally authorized representative, where allowed) has been informed of the nature of the study, agrees to its provisions, and has provided written informed consent approved by the appropriate institutional review board (IRB)/Regional Ethics Board (REB)/Ethics Committee (EC).

Exclusion Criteria:

1. Pregnant or nursing patients and those who plan pregnancy in the period up to one year following the index procedure. Female patients of childbearing potential must have a negative pregnancy test (per site standard test) within 7 days prior to index procedure.
2. Anatomic conditions that would prevent performance of an LAA occlusion procedure (e.g., atrial septal defect (ASD) requiring closure, high-risk patent foramen ovale (PFO) requiring closure, a highly mobile inter-atrial septal aneurysm precluding a safe TSP, presence of a PFO/ASD closure device, history of surgical ASD repair or history of surgical LAAO closure)
3. Atrial fibrillation that is defined by a single occurrence or that is transient or reversible (e.g., secondary thyroid disorders, acute alcohol intoxication, trauma, recent major surgical procedures)
4. A medical condition (other than atrial fibrillation) that mandates long-term oral anticoagulation (e.g., history of unprovoked deep vein thrombosis or pulmonary embolism, or prosthetic mechanical heart valve)
5. History of bleeding diathesis or coagulopathy, or patients in whom antiplatelet and/or anticoagulant therapy is contraindicated
6. Documented active systemic infection
7. Symptomatic carotid artery disease (defined as \>50% stenosis with symptoms of ipsilateral transient or visual TIA evidenced by amaurosis fugax, ipsilateral hemispheric TIAs or ipsilateral stroke); if subject has a history of carotid stent or endarterectomy the subject is eligible if there is \<50% stenosis noted at the site of prior treatment
8. Recent (within 30 days of index procedure) or planned (within 60 days post-procedure) cardiac or major non-cardiac interventional or surgical procedure
9. Recent (within 30 days of index procedure) stroke or transient ischemic attack
10. Recent (within 30 days of index procedure) myocardial infarction
11. Vascular access precluding delivery of implant with catheter-based system
12. Severe heart failure (New York Heart Association Class IV)
13. Prior cardiac transplant, history of mitral valve replacement or transcatheter mitral valve intervention, or any prosthetic mechanical valve implant
14. Renal insufficiency, defined as estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73 m2 (by the Modification of Diet in Renal Disease equation)
15. Platelet count \<75,000 cells/mm3 or \>700,000 cells/mm3, or white blood cell count \<3,000 cells/mm3
16. Known allergy, hypersensitivity or contraindication to aspirin, heparin, or device materials (e.g., nickel, titanium) that would preclude any P2Y12 inhibitor therapy, or the patient has contrast sensitivity that cannot be adequately pre-medicated
17. Actively enrolled or plans to enroll in a concurrent clinical study in which the active treatment arm may confound the results of this trial
18. Unable to undergo general anesthesia
19. Known other medical illness or known history of substance abuse that may cause non-compliance with the protocol or protocol-specified medication regimen, confound the data interpretation, or is associated with a life expectancy of less than 5 years
20. A condition which precludes adequate transesophageal echocardiographic assessment

Echo exclusion criteria:

1. Left atrial appendage anatomy which cannot accommodate a commercially available control device or the CLAAS Implant per manufacturer IFU (e.g., the anatomy and sizing must be appropriate for both the investigational (CLAAS) and a commercially available device in order to be enrolled in the trial)
2. Intracardiac thrombus or dense spontaneous echo contrast consistent with thrombus, as visualized by TEE prior to implant
3. Left ventricular ejection fraction (LVEF) \<30%
4. Moderate or large circumferential pericardial effusion \>10 mm or symptomatic pericardial effusion, signs or symptoms of acute or chronic pericarditis, or evidence of tamponade physiology
5. Atrial septal defect that warrants closure
6. High risk patent foramen ovale (PFO), defined as an atrial septal aneurysm (excursion \>15 mm or length \> 15 mm) or large shunt (early \[within 3 beats\] and/or substantial passage of bubbles, e.g., \>20)
7. Moderate or severe mitral valve stenosis (mitral valve area \<1.5 cm2)
8. Complex atheroma with mobile plaque of the descending aorta and/or aortic arch
9. Evidence of cardiac tumor

Primary outcomes:
measure: Procedure-related complications, all-cause death, major bleeding
timeFrame: 12 months
measure: Ischemic stroke and systemic embolism
timeFrame: 18 months
Secondary outcomes:
measure: All Cause Mortality
timeFrame: 18 months
measure: Myocardial Infarction
timeFrame: 7 days
measure: Neurologic Events
timeFrame: 45 days
measure: Closure Success
timeFrame: 12 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Grandview Medical Center
state: Alabama
city: Phoenix
country: United States
facility: Abrazo Arizona Heart Hospital
state: Arizona
city: Scottsdale
country: United States
facility: HonorHealth
state: Arizona
city: Tucson
country: United States
facility: Pima Heart & Vascular
state: Arizona
city: Jonesboro
country: United States
facility: St. Bernard's Medical Center
state: Arkansas
city: Santa Monica
country: United States
facility: Pacific Heart Institute
state: California
city: Ventura
country: United States
facility: Community Memorial Hospital Ventura
state: California
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Jacksonville
country: United States
facility: Ascension St. Vincent's Jacksonville
state: Florida
city: Largo
country: United States
facility: Largo Medical Center
state: Florida
city: Miami
country: United States
facility: Baptist Hospital of Miami
state: Florida
city: Tampa
country: United States
facility: USF - Tampa General Hospital
state: Florida
city: Atlanta
country: United States
facility: Piedmont Health Institute
state: Georgia
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Atlanta
country: United States
facility: Northside Hospital, Inc
state: Georgia
city: Marietta
country: United States
facility: WellStar Kennestone Hospital
state: Georgia
city: Naperville
country: United States
facility: Midwest Cardiovascular Institute
state: Illinois
city: Indianapolis
country: United States
facility: Ascension St. Vincent - Carmel, IN
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Wichita
country: United States
facility: Cardiovascular Research Institute of Kansas
state: Kansas
city: Houma
country: United States
facility: Terrebone - Cardiovascular Institute of the South
state: Louisiana
city: Baltimore
country: United States
facility: Medstar Union Memorial Hospital
state: Maryland
city: Burlington
country: United States
facility: Lahey Hospital & Medical Centeer
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford St. John Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Corewell Health
state: Michigan
city: Southfield
country: United States
facility: Henry Ford Providence Southfield Hospital
state: Michigan
city: Maplewood
country: United States
facility: M Health Fairview St. John's Hospital
state: Minnesota
city: Saint Cloud
country: United States
facility: CentraCare Heart and Vascular Center
state: Minnesota
city: Tupelo
country: United States
facility: North Mississippi Medical Center
state: Mississippi
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City
state: Missouri
city: Overland
country: United States
facility: Kansas City Cardiac Arrhythmia Research, LLC
state: Missouri
city: Omaha
country: United States
facility: CHI Health / CommonSpirit Research Institute
state: Nebraska
city: Manchester
country: United States
facility: Catholic Medical Center
state: New Hampshire
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Haddon Heights
country: United States
facility: Cooper University - Heart House
state: New Jersey
city: Albany
country: United States
facility: Albany Medical Center / Capital Cardiology Associates
state: New York
city: Buffalo
country: United States
facility: University of Buffalo / Kaleida Health
state: New York
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: Asheville
country: United States
facility: Mission Hospital
state: North Carolina
city: Columbus
country: United States
facility: Ohio Health Research Institute
state: Ohio
city: Mechanicsburg
country: United States
facility: UPMC Harrisburg
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Heart Institute
state: Pennsylvania
city: Providence
country: United States
facility: Lifespan Health System
state: Rhode Island
city: North Charleston
country: United States
facility: Trident Medical Center
state: South Carolina
city: Chattanooga
country: United States
facility: Erlanger Health System
state: Tennessee
city: Knoxville
country: United States
facility: Tennova Healthcare - Turkey Creek Medical Center
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: Houston Methodist
state: Texas
city: Houston
country: United States
facility: Memorial Hermann Memorial City Medical Center
state: Texas
city: Tyler
country: United States
facility: CHRISTUS Health
state: Texas
city: Norfolk
country: United States
facility: Senatra Norfolk
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Richmond
country: United States
facility: Chippenham Hospital
state: Virginia
city: Roanoke
country: United States
facility: Carilion Clinic
state: Virginia
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
city: Tbilisi
country: Georgia
facility: Chapidze Heart Disease Center
city: Tbilisi
country: Georgia
facility: Israeli-Georgian Medical Research Clinic Helsicore
city: Tbilisi
country: Georgia
facility: Tbilisi Heart and Vascular Clinic
city: Tbilisi
country: Georgia
facility: Tbilisi Heart Center
city: Chilanzar
country: Uzbekistan
facility: Republican Specialized Center for Surgery named after V. Vakhidov
state: Tashkent
city: Olmazor
country: Uzbekistan
facility: AKFA Medline
state: Tashkent
Study officials:
affiliation: Lankenau Heart Institute
name: William Gray, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Pacific Heart Institute
name: Shephal Doshi, M.D.
role: PRINCIPAL_INVESTIGATOR
References: