Clinical trial NCT03618095: REPRISE IV: LOTUS Edge Valve System in Intermediate Surgical Risk Subjects
Official title: REPRISE IV: REpositionable Percutaneous Replacement of Stenotic Aortic Valve Through Implantation of LOTUS Edge Valve System in IntermediatE Surgical Risk Subjects
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Aortic Valve Stenosis
Lead sponsor: Boston Scientific Corporation
Sponsor class: INDUSTRY
First posted: 2018-08-07
Enrollment: 382
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Evaluation of Lotus Edge to treat patients with aortic stenosis. A single intervention is being evaluated in 3 study arms, the roll-in, main and bicuspid cohorts.
Primary purpose: TREATMENT

Brief summary: REPRISE IV: REpositionable Percutaneous Replacement of Stenotic Aortic Valve through Implantation of LOTUS Edge Valve System in IntermediatE Surgical Risk Subjects

Detailed description: To evaluate safety and effectiveness of the LOTUS Edge™ Valve System when used with the Lotus™ or iSleeve™ Introducer Sets for transcatheter aortic valve replacement (TAVR) in symptomatic subjects with severe aortic stenosis who are considered at intermediate risk for surgical valve replacement including those who have a bicuspid native valve.

Eligibility criteria: Inclusion Criteria:

* Subject has documented severe aortic stenosis defined as initial aortic valve area (AVA) ≤1.0 cm2 (or AVA index ≤0.6 cm2/m2) AND a mean pressure gradient ≥40 mm Hg OR maximal aortic valve velocity ≥4.0 m/s OR Doppler velocity index ≤0.25 as measured by echocardiography and/or invasive hemodynamics. Note: In cases of low flow, low gradient aortic stenosis with left ventricular dysfunction (ejection fraction \<50%), dobutamine can be used to assess the grade of aortic stenosis (maximum dobutamine dose of 20 mcg/kg/min recommended)c; the subject may be enrolled if echocardiographic criteria are met with this augmentation. (IC1)
* A subject in the Bicuspid Aortic Valve Nested Registry cohort must have a documented Sievers Type 0 or Sievers Type 1 bicuspid aortic valve based on computed tomography (CT) assessment and confirmed by the CT core lab with hemodynamic parameters that meet the criteria in IC1.
* Subject has a documented aortic annulus size of ≥20 mm and ≤27 mm based on the center's assessment of pre-procedure diagnostic imaging (and confirmed by the Case Review Committee \[CRC\]).
* Subject has symptomatic aortic valve stenosis per IC1 definition above with New York Heart Association (NYHA) Functional Class ≥ II.
* Heart team (which must include an experienced cardiac interventionalist and an experienced cardiac surgeon) agrees that the subject is at intermediate risk of operative mortality (≥3% and \<8% at 30 days based on the Society of Thoracic Surgeons \[STS\] risk score and other clinical comorbidities unmeasured by the risk calculator) and TAVR is appropriate. Note: Risk of operative mortality must be assessed via an in-person evaluation by a center cardiac surgeon and must be confirmed by the CRC (which must include an experienced cardiac surgeon).
* Heart team agrees that the subject is likely to benefit from valve replacement. IC7. Subject (or legal representative) has been informed of the study requirements and the treatment procedures, and provides written informed consent.
* Subject, family member, and/or legal representative agree(s) and subject is capable of returning to the study hospital for all required scheduled follow-up visits.
* Subject is expected to be able to take the protocol-required adjunctive pharmacologic therapy.

Exclusion Criteria:

* Subject has a unicuspid or bicuspid aortic valve (not applicable to subjects in the Bicuspid Nested Registry cohort).
* Subjects in the Bicuspid Nested Registry cohort will have a documented Sievers Type 0 or Sievers Type 1 bicuspid aortic valve based on CT assessment and confirmed by the CT core lab. Subjects are not eligible for inclusion in the Bicuspid Nested Registry cohort if the maximum diameter of the ascending aorta is \>45 mm or if the subject has another indication for aortic root replacement. Subjects with a Sievers Type 2 bicuspid valve are not eligible for enrollment in any study cohort.
* Subject has had an acute myocardial infarction (MI) within 30 days prior to the index procedure (defined as Q-wave MI or non-Q-wave MI with total creatine kinase (CK) elevation ≥ twice normal in the presence of creatine kinase-myoglobin band (CK-MB) elevation and/or troponin elevation).
* Subject has had a cerebrovascular accident or transient ischemic attack clinically confirmed by a neurologist or neuroimaging within the past 6 months prior to study enrollment.
* Subject is on renal replacement therapy or has Glomerular Filtration Rate (GFR) \<20 (based on hospital preferred method). See AEC1 below if subject is in the CT Imaging Substudy.
* Subject has a pre-existing prosthetic aortic or mitral valve.
* Subject has severe (4+) aortic, tricuspid, or mitral regurgitation.
* Subject has moderate to severe mitral stenosis (mitral valve area ≤1.5 cm2 and diastolic pressure half-time ≥150 ms, Stage C or Dc).
* Subject has a need for emergency surgery for any reason.
* Subject has a history of endocarditis within 6 months of index procedure or evidence of an active systemic infection or sepsis.
* Subject has echocardiographic evidence of new intra-cardiac vegetation or intraventricular or paravalvular thrombus requiring intervention.
* Subject has platelet count \<50,000 cells/mm3 or \>700,000 cells/mm3, or white blood cell count \<1,000 cells/mm3.
* Subject will refuse transfusions or has had a gastrointestinal bleed requiring hospitalization or transfusion within the past 3 months, or has other clinically significant bleeding diathesis or coagulopathy that would preclude treatment with required antiplatelet regimen.
* Subject has known hypersensitivity to contrast agents that cannot be adequately pre-medicated, or has known hypersensitivity to aspirin, all P2Y12 inhibitors, heparin, nickel, tantalum, titanium, or polyurethanes.
* Subject has a life expectancy of less than 24 months due to non-cardiac, comorbid conditions based on the assessment of the investigator at the time of enrollment.
* Subject has hypertrophic cardiomyopathy.
* Subject has any therapeutic invasive cardiac or vascular procedure within 30 days prior to the index procedure (except for balloon aortic valvuloplasty or pacemaker or implantable cardioverter defibrillator implantation, which are allowed).
* Subject has multivessel coronary artery disease with a Syntax score \>22, and/or an unprotected left main coronary artery.
* Subject has severe left ventricular dysfunction with ejection fraction \<20%.
* Subject is in cardiogenic shock or has hemodynamic instability requiring inotropic support or mechanical support devices.
* Subject has arterial access that is not acceptable for the study device delivery system as defined in the device Instructions For Use.
* Subject has severe vascular disease that would preclude safe access (e.g., aneurysm with thrombus that cannot be crossed safely; marked tortuosity; significant narrowing of the abdominal aorta; severe unfolding of the thoracic aorta; or thick, protruding, ulcerated atheroma in the aortic arch).
* Subject has current problems with substance abuse (e.g., alcohol, etc.) that may interfere with the subject's participation in this study.
* Subject is participating in another investigational drug or device study that has not reached its primary endpoint.
* Subject has untreated conduction system disorder (e.g., Type II second degree atrioventricular block) that in the opinion of the treating physician is clinically significant and requires a pacemaker implantation. Enrollment is permissible after permanent pacemaker implantation.
* Subject has severe incapacitating dementia.

Primary outcomes:
measure: Composite of All-cause Mortality and All Stroke.
timeFrame: 1 year post index procedure and device implantation
Secondary outcomes:
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Huntsville Hospital
state: Alabama
city: Tucson
country: United States
facility: Tucson Medical Center
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Heart Hospital
state: Arkansas
city: Burlingame
country: United States
facility: Mills-Peninsula Medical Center - Sutter Health
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente Los Angeles Medical Center
state: California
city: Los Angeles
country: United States
facility: USC Medical Center
state: California
city: Denver
country: United States
facility: Saint Joseph Hospital
state: Colorado
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Washington
country: United States
facility: Medstar Heart and Vascular Institute
state: District of Columbia
city: Atlantis
country: United States
facility: JFK Medical Center
state: Florida
city: Gainesville
country: United States
facility: North Florida Regional Medical Center
state: Florida
city: Orlando
country: United States
facility: AdventHealth Orlando
state: Florida
city: Atlanta
country: United States
facility: Piedmont Heart Institute
state: Georgia
city: Marietta
country: United States
facility: Wellstar Research Institute
state: Georgia
city: Evanston
country: United States
facility: NorthShore University HealthSystem
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Health - Methodist Hospital
state: Indiana
city: Wichita
country: United States
facility: Via Christi Hospital
state: Kansas
city: New Orleans
country: United States
facility: Ochsner Medical Center
state: Louisiana
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Fall River
country: United States
facility: Charlton Memorial Hospital - Southcoast Health
state: Massachusetts
city: Grand Rapids
country: United States
facility: Spectrum Health - Grand Rapids
state: Michigan
city: Petoskey
country: United States
facility: Cardiac & Vascular Research Center of Northern Michigan
state: Michigan
city: Royal Oak
country: United States
facility: Beaumont Hospital
state: Michigan
city: Saint Cloud
country: United States
facility: St. Cloud Hospital
state: Minnesota
city: Englewood
country: United States
facility: Englewood Hospital
state: New Jersey
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: Mineola
country: United States
facility: NYU Winthrop Hospital
state: New York
city: New York
country: United States
facility: NYU Langone Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center/NewYork Presbyterian Hospital
state: New York
city: Charlotte
country: United States
facility: Novant Health Heart & Vascular Institute - Charlotte
state: North Carolina
city: Raleigh
country: United States
facility: UNC Rex Hospital
state: North Carolina
city: Cincinnati
country: United States
facility: The Lindner Center for Research and Education
state: Ohio
city: Portland
country: United States
facility: Providence St. Vincent Medical Center
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Greenville
country: United States
facility: Greenville Memorial Hospital - Prisma Health
state: South Carolina
city: Nashville
country: United States
facility: Centennial Medical Center
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: Memorial Hermann - Texas Medical Center
state: Texas
city: Houston
country: United States
facility: University of Texas - Memorial Hermann Southwest
state: Texas
city: Plano
country: United States
facility: Baylor Scott & White The Heart Hospital
state: Texas
city: Annandale
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Morgantown
country: United States
facility: WVU Heart & Vascular Institute
state: West Virginia
city: Milwaukee
country: United States
facility: Aurora St. Luke's Medical Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Froedtert Hospital - Medical College of Wisconsin
state: Wisconsin
city: Clayton
country: Australia
facility: Monash Cardiovascular Research Centre
state: Victoria
Study officials:
affiliation: Piedmont Heart Institute
name: Christopher U. Meduri, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Piedmont Heart Institute
name: Vinod H. Thourani, MD
role: PRINCIPAL_INVESTIGATOR
References: