Safety and Efficacy Study of Lotus Valve for Transcatheter Aortic Valve Replacement

Not Applicable

Terminated

Conditions: Aortic Stenosis

Interventions: Device: Lotus Valve System
Device: CoreValve/Evolut R Transcatheter Aortic Valve Replacement System
Device: LOTUS Edge Valve System

Registration Number: NCT02202434

Lead Sponsor: Boston Scientific Corporation

Brief Summary: The objective of this study is to evaluate the safety and effectiveness of the Lotus™ Valve System and LOTUS Edge™ Valve System for transcatheter aortic valve replacement (TAVR) in symptomatic subjects with calcific, severe native aortic stenosis who are considered at extreme or high risk for surgical valve replacement.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 1425

Inclusion Criteria

Subject has documented calcific, severe native aortic stenosis with an initial aortic valve area (AVA) of ≤1.0 cm2 (or AVA index of ≤0.6 cm2/m2) and a mean pressure gradient >40 mm Hg or jet velocity >4.0 m/s, as measured by echocardiography and/or invasive hemodynamics
Subject has a documented aortic annulus size of ≥18 mm and ≤29 mm based on the center's assessment of pre-procedure diagnostic imaging (and confirmed by the Case Review Committee [CRC]) and, for the randomized cohort, is deemed treatable with an available size of both test and control device. For the U.S. Continued Access Study cohort the acceptable aortic annulus size is ≥20 mm and ≤27 mm.
Subject has symptomatic aortic valve stenosis with New York Heart Association (NYHA) Functional Class ≥ II
There is agreement by the heart team (which must include a site investigator interventionalist and a site investigator cardiac surgeon) that subject is at high or extreme operative risk for surgical valve replacement (see note below for definitions of extreme and high risk, the required level of surgical assessment, and CRC confirmation) and that TAVR is appropriate. Additionally, subject has at least one of the following.
- Society of Thoracic Surgeons (STS) score ≥8% -OR-
- If STS <8, subject has at least one of the following conditions: Hostile chest, porcelain aorta, severe pulmonary hypertension (>60 mmHg), prior chest radiation therapy, coronary artery bypass graft(s) at risk with re-operation, severe lung disease (need for supplemental oxygen, forced expiratory volume in 1 second [FEV1] <50% of predicted, diffusing capacity of the lungs for carbon monoxide [DLCO] <60%, or other evidence of severe pulmonary dysfunction), neuromuscular disease that creates risk for mechanical ventilation or rehabilitation after surgical aortic valve replacement, orthopedic disease that creates risk for rehabilitation after surgical aortic valve replacement, Childs Class A or B liver disease (subjects with Childs Class C disease are not eligible for inclusion in this trial), frailty as indicated by at least one of the following: 5-meter walk >6 seconds, Katz Assessment of Daily Living (Katz ADL) score of 3/6 or less, body mass index <21, wheelchair bound, unable to live independently, age ≥90 years, other evidence that subject is at high or extreme risk for surgical valve replacement (CRC must confirm agreement with site heart team that subject meets high or extreme risk definition)
Heart team (which must include a cardiac interventionalist and an experienced cardiac surgeon) assessment that the subject is likely to benefit from valve replacement.
Subject (or legal representative) understands 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.

Note: Extreme operative risk and high operative risk are defined as follows: Extreme Operative Risk: Predicted operative mortality or serious, irreversible morbidity risk ≥50% at 30 days; High Operative Risk: Predicted operative mortality or serious, irreversible morbidity risk ≥15% at 30 days. Risk of operative mortality and morbidity 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).

Exclusion Criteria

Subject has a congenital unicuspid or bicuspid aortic valve.
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 within the past 6 months prior to study enrollment.
Subject has end-stage renal disease or has glomerular filtration rate (GFR) <20 (based on Cockcroft-Gault formula).
Subject has a pre-existing prosthetic aortic or mitral valve.
Subject has severe (4+) aortic, tricuspid, or mitral regurgitation.
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 mass, vegetation or intraventricular or paravalvular thrombus requiring intervention.
Subject has (hemoglobin) Hgb <9 g/dL, platelet count <50,000 cells/mm3 or >700,000 cells/mm3, or white blood cell count <1,000 cells/mm3.
Subject requires chronic anticoagulation therapy after the implant procedure and cannot be treated with warfarin (other anticoagulants are not permitted in the first month) for at least 1 month concomitant with either aspirin or clopidogrel.
Subject 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, or will refuse transfusions.
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 12 months due to non-cardiac, comorbid conditions based on the assessment of the investigator at the time of enrollment.
Subject has hypertrophic obstructive 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 implantation, which are allowed).
Subject has untreated coronary artery disease, which in the opinion of the treating physician is clinically significant and requires revascularization.
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 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 symptomatic carotid or vertebral disease).
Subject has thick (>5 mm) protruding or ulcerated atheroma in the aortic arch
Subject has arterial access that is not acceptable for the test and control device delivery systems as defined in the device Instructions For Use.
Subject has current problems with substance abuse (e.g., alcohol, etc.).
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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lotus Valve System - Randomized	Lotus Valve System	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System
CoreValve TAVR System - Randomized	CoreValve/Evolut R Transcatheter Aortic Valve Replacement System	Transcatheter aortic valve replacement (TAVR) with CoreValve/Evolut R Transcatheter Aortic Valve Replacement System
Lotus Valve Sytem - Single-arm 21mm Cohort	Lotus Valve System	Transcatheter aortic valve replacement (TAVR) with 21mm Lotus Valve System
Lotus Valve System - Single-arm Roll-in Cohort	Lotus Valve System	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System
Lotus Valve System - Single-arm Continued Access Cohort	Lotus Valve System	Transcatheter aortic valve replacement (TAVR) with Lotus Valve System
LOTUS Edge Valve System - Single-arm Edge Nested Registry	LOTUS Edge Valve System	Transcatheter aortic valve replacement (TAVR) with 23mm, 25mm and 27mm LOTUS Edge Valve System.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Events Included in the Primary Safety Endpoint	30 days following procedure	Composite of all-cause mortality, stroke, life-threatening and major bleeding events, stage 2 or 3 acute kidney injury, or major vascular complications
Percentage of Participants With Events Included in the Primary Effectiveness Endpoint	1 year following procedure	Composite of all-cause mortality, disabling stroke, or moderate or greater paravalvular aortic regurgitation (based on core lab assessment).

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Moderate or Greater Paravalvular Aortic Regurgitation	1 year following procedure	Moderate or greater paravalvular aortic regurgitation based on Independent echocardiographic core lab assessment performed using the Unifying 5-Class Grading Scheme for Aortic Regurgitation by Pibarot et al (J Am Coll Cardiol Img 2015: 8: 340-60). The grading scheme ranges from Trace (the least clinically significant) to severe (the most clinically significant).

Trial Locations

Locations (58): Scottsdale Healthcare - Shea
🇺🇸
Scottsdale, Arizona, United States
Cedars-Sinai Medical Center
🇺🇸
Los Angeles, California, United States
Scripps Clinic
🇺🇸
La Jolla, California, United States
Veteran's Administration Palo Alto Medical Center
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Palo Alto, California, United States
Stanford University Medical Center
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Stanford, California, United States
Morton Plant Mease Healthcare System
🇺🇸
Clearwater, Florida, United States
Delray Medical Center
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Delray Beach, Florida, United States
Evanston Hospital
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Evanston, Illinois, United States
Piedmont Hospital
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Atlanta, Georgia, United States
Emory University Hospital
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Atlanta, Georgia, United States
St. John's Hospital - Prairie Cardiovascular Consultants
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Springfield, Illinois, United States
Union Memorial Hospital
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Baltimore, Maryland, United States
Cardiac & Vascular Rearch Center of Northern Michigan - Northern Michigan Hospital
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Petoskey, Michigan, United States
William Beaumont Hospital
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Royal Oak, Michigan, United States
Washington University School of Medicine - Barnes Jewish Medical Center
🇺🇸
Saint Louis, Missouri, United States
Morristown Memorial Hospital
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Morristown, New Jersey, United States
Kaleida Health
🇺🇸
Buffalo, New York, United States
Columbia University Medical Center
🇺🇸
New York, New York, United States
NC Heart and Vascular Research - Rex Hospital
🇺🇸
Raleigh, North Carolina, United States
Hospital of the University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
Medical City Dallas Hospital
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Dallas, Texas, United States
Baylor Heart and Vascular Hospital
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Dallas, Texas, United States
Inova Fairfax Hospital
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Falls Church, Virginia, United States
The Prince Charles Hospital
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Chermside, Queensland, Australia
Monash Medical Centre
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Clayton, Victoria, Australia
Clinique Pasteur
🇫🇷
Toulouse, Midi-Pyrenees, France
Centre Hôpital Universitaire Rangueil
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Toulouse, France
Universitares Herzzentrum UKE (Hamburg)
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Hamburg, Germany
Herzzentrum Universität Leipzig
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Leipzig, Saxony, Germany
Erasmus MC - University Medical Center Rotterdam
🇳🇱
Rotterdam, Netherlands
University of Miami Hospital
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Miami, Florida, United States
Baptist Cardiac and Vascular Institute
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Miami, Florida, United States
St. Vincent's Hospital
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Indianapolis, Indiana, United States
Beth Israel Deaconess Medical Center
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Boston, Massachusetts, United States
Cleveland Clinic Foundation
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Cleveland, Ohio, United States
Ohio State University Medical Center
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Columbus, Ohio, United States
Ohio Health Research and Innovation Institute - Riverside Methodist Hospital
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Columbus, Ohio, United States
University of Pittsburgh Medical Center
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Pittsburgh, Pennsylvania, United States
Methodist DeBakey Heart & Vascular Center
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Houston, Texas, United States
University of Washington Medical Center
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Seattle, Washington, United States
Swedish Medical Center
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Seattle, Washington, United States
University of Kansas Hospital
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Kansas City, Kansas, United States
North Shore University Hospital
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Manhasset, New York, United States
McGill University Health Centre, Royal Victoria Hospital
🇨🇦
Montreal, Quebec, Canada
Washington Hospital Center
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Washington, District of Columbia, United States
Banner Good Samaritan
🇺🇸
Phoenix, Arizona, United States
Abbott Northwestern Hospital - Minneapolis Heart Institute
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Minneapolis, Minnesota, United States
University of Minnesota Medical Center
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Minneapolis, Minnesota, United States
Mayo Clinic
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Rochester, Minnesota, United States
Duke University Medical Center
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Durham, North Carolina, United States
Lindner Center for Research and Education at The Christ Hospital
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Cincinnati, Ohio, United States
Providence St. Vincent Medical Center
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Portland, Oregon, United States
Methodist Heart Hospital
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San Antonio, Texas, United States
Aurora St. Luke's Medical Center
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Milwaukee, Wisconsin, United States
University of California at Davis Medical Center
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Sacramento, California, United States
University of Michigan
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Ann Arbor, Michigan, United States
Wake Forest University School of Medicine
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Winston-Salem, North Carolina, United States
Providence Health - St. Paul's Hospital
🇨🇦
Vancouver, British Columbia, Canada