REPRISE IV: LOTUS Edge Valve System in Intermediate Surgical Risk Subjects

Aortic Valve Stenosis Clinical Trial

— REPRISE IV  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03618095
• Other study ID #: S2354
• Status: Terminated
• Phase: N/A
• Start date: January 14, 2019
• Est. completion date: March 31, 2021

Study information

• Verified date: October 2022
• Source: Boston Scientific Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 382
• Est. completion date: March 31, 2021
• Est. primary completion date: March 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Aortic Valve Stenosis

Intervention

Device:
• LOTUS Edge Valve System
TAVR with the LOTUS Edge Valve System

Locations

Country	Name	City	State
Australia	Monash Cardiovascular Research Centre	Clayton	Victoria
United States	Inova Fairfax Hospital	Annandale	Virginia
United States	Piedmont Heart Institute	Atlanta	Georgia
United States	JFK Medical Center	Atlantis	Florida
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Mills-Peninsula Medical Center - Sutter Health	Burlingame	California
United States	Novant Health Heart & Vascular Institute - Charlotte	Charlotte	North Carolina
United States	The Lindner Center for Research and Education	Cincinnati	Ohio
United States	Saint Joseph Hospital	Denver	Colorado
United States	Englewood Hospital	Englewood	New Jersey
United States	NorthShore University HealthSystem	Evanston	Illinois
United States	Charlton Memorial Hospital - Southcoast Health	Fall River	Massachusetts
United States	North Florida Regional Medical Center	Gainesville	Florida
United States	Spectrum Health - Grand Rapids	Grand Rapids	Michigan
United States	Greenville Memorial Hospital - Prisma Health	Greenville	South Carolina
United States	Memorial Hermann - Texas Medical Center	Houston	Texas
United States	University of Texas - Memorial Hermann Southwest	Houston	Texas
United States	Huntsville Hospital	Huntsville	Alabama
United States	Indiana University Health - Methodist Hospital	Indianapolis	Indiana
United States	Arkansas Heart Hospital	Little Rock	Arkansas
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	USC Medical Center	Los Angeles	California
United States	North Shore University Hospital	Manhasset	New York
United States	Wellstar Research Institute	Marietta	Georgia
United States	Aurora St. Luke's Medical Center	Milwaukee	Wisconsin
United States	Froedtert Hospital - Medical College of Wisconsin	Milwaukee	Wisconsin
United States	NYU Winthrop Hospital	Mineola	New York
United States	WVU Heart & Vascular Institute	Morgantown	West Virginia
United States	Morristown Medical Center	Morristown	New Jersey
United States	Centennial Medical Center	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	Ochsner Medical Center	New Orleans	Louisiana
United States	Columbia University Medical Center/NewYork Presbyterian Hospital	New York	New York
United States	NYU Langone Medical Center	New York	New York
United States	AdventHealth Orlando	Orlando	Florida
United States	Cardiac & Vascular Research Center of Northern Michigan	Petoskey	Michigan
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Baylor Scott & White The Heart Hospital	Plano	Texas
United States	Providence St. Vincent Medical Center	Portland	Oregon
United States	UNC Rex Hospital	Raleigh	North Carolina
United States	Beaumont Hospital	Royal Oak	Michigan
United States	St. Cloud Hospital	Saint Cloud	Minnesota
United States	Swedish Medical Center	Seattle	Washington
United States	University of Washington	Seattle	Washington
United States	Tucson Medical Center	Tucson	Arizona
United States	Medstar Heart and Vascular Institute	Washington	District of Columbia
United States	Via Christi Hospital	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Boston Scientific Corporation

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite of All-cause Mortality and All Stroke.	Pre-specified primary outcome measure in the protocol for the Main Cohort only. Critical safety events that are observed in the elderly population undergoing TAVR; assessments recommended by Valve Academic Research Consortium (VARC)	1 year post index procedure and device implantation