MedPath

REPRISE Next Generation Delivery System

Not Applicable
Completed
Conditions
Aortic Stenosis
Interventions
Device: Lotus Valve and LOTUS Edge Valve System
Registration Number
NCT02329496
Lead Sponsor
Boston Scientific Corporation
Brief Summary

To confirm the acute performance and safety of the Lotus™ Valve with the Next Generation Delivery System for transcatheter aortic valve replacement (TAVR) in symptomatic patients with severe calcific aortic stenosis who are considered high risk for surgical valve replacement.

Detailed Description

This clinical study is a prospective single-arm study designed to demonstrate that the acute performance and safety of the LOTUS Edge Valve System when used with the iSleeve Introducer Set or current Lotus Introducer Set are consistent with the results of the Lotus Valve System used in the REPRISE II study, when delivered and deployed in symptomatic subjects who have severe calcific aortic valve stenosis and who are at high risk for surgical aortic valve replacement (SAVR).

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
38
Inclusion Criteria
  1. Subject is ≥70 years of age

  2. Subject has documented calcific native aortic valve stenosis with an initial aortic valve area (AVA) of ≤1.0 cm2 (or AVA index of ≤0.6 cm2/m2) and either a mean pressure gradient ≥40 mm Hg or a jet velocity ≥4 m/s, as measured by echocardiography.

  3. Subject has a documented aortic annulus size between ≥20 and ≤27.5 mm based on pre-procedure diagnostic imaging

  4. Subject has symptomatic aortic valve stenosis with NYHA Functional Class ≥ II.

  5. Subject is considered high risk for surgical valve replacement based on at least one of the following:

    • Society of Thoracic Surgeons (STS) score ≥8%, and/or
    • Agreement by the heart team (which must include an in-person evaluation by an experienced cardiac surgeon) that subject is at high operative risk of serious morbidity or mortality with surgical valve replacement.
  6. Heart team (which must include an experienced cardiac surgeon) assessment that the subject is likely to benefit from valve replacement

  7. Subject (or legal representative) understands the study requirements and the treatment procedures, and provides written informed consent.

  8. 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.

Exclusion Criteria
  1. Subject has a congenital unicuspid or bicuspid aortic valve.
  2. Subject with an acute myocardial infarction within 30 days of the index procedure (defined as Q-wave MI or non-Q-wave MI with total CK elevation ≥ twice normal in the presence of creatine kinase-myoglobin band (CK-MB) elevation and/or troponin level elevation).
  3. Subject has had a cerebrovascular accident or transient ischemic attack within the past 6 months, or has any permanent neurologic defect prior to study enrollment.
  4. Subject is on dialysis or has serum creatinine level >3.0 mg/dL or 265 µml/L.
  5. Subject has a pre-existing prosthetic heart valve (aortic or mitral) or a prosthetic ring in any position.
  6. Subject has ≥3+ mitral regurgitation, ≥3+ aortic regurgitation or ≥3+ tricuspid regurgitation (i.e., subject cannot have more than moderate mitral, aortic or tricuspid regurgitation).
  7. Subject has a need for emergency surgery for any reason.
  8. Subject has a history of endocarditis within 12 months of index procedure or evidence of an active systemic infection or sepsis.
  9. Subject has echocardiographic evidence of intra-cardiac mass, thrombus or vegetation.
  10. Subject has Hgb <9 g/dL, platelet count <50,000 cells/mm3 or >700,000 cells/mm3, or white blood cell count <1,000 cells/mm3.
  11. Subject is receiving chronic (≥72 hours) anticoagulation therapy (warfarin), and cannot tolerate concomitant therapy with aspirin or clopidogrel (subjects who require chronic anticoagulation must additionally be able to be treated with either aspirin or clopidogrel).*
  12. Subject has active peptic ulcer disease or gastrointestinal bleed within the past 3 months, other bleeding diathesis or coagulopathy or will refuse transfusions.
  13. Subject has known hypersensitivity to contrast agents that cannot be adequately pre-medicated, or has known hypersensitivity to aspirin, all thienopyridines, heparin, nickel, titanium, or polyurethanes.
  14. Subject has a life expectancy of less than 12 months due to non-cardiac, co-morbid conditions based on the assessment of the investigator at the time of enrollment.
  15. Subject has hypertrophic obstructive cardiomyopathy.
  16. Subject has any therapeutic invasive cardiac procedure within 30 days prior to the index procedure (except for balloon aortic valvuloplasty and pacemaker implantation which are allowed).
  17. Subject has untreated coronary artery disease, which in the opinion of the treating physician, is clinically significant and requires revascularization.
  18. Subject has documented left ventricular ejection fraction <30%.
  19. Subject is in cardiogenic shock or has hemodynamic instability requiring inotropic support or mechanical support devices.
  20. Subject has severe peripheral vascular disease (including aneurysm defined as maximal luminal diameter >5 cm or with documented presence of thrombus, marked tortuosity, narrowing of the abdominal aorta, severe unfolding of the thoracic aorta or thick [>5 mm] protruding or ulcerated atheroma in the aortic arch) or symptomatic carotid or vertebral disease.
  21. Femoral artery lumen of <6.0 mm for subjects requiring 23 mm valve size or <6.5 mm for subjects requiring 27 mm valve size, or severe iliofemoral tortuosity or calcification that would prevent safe placement of the introducer sheath.
  22. Current problems with substance abuse (e.g., alcohol, etc.).
  23. Subject is participating in another investigational drug or device study that has not reached its primary endpoint.
  24. 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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Lotus Valve and LOTUS Edge Valve SystemLotus Valve and LOTUS Edge Valve SystemTranscatheter aortic valve replacement (TAVR) with Lotus Valve System with the Next Generation Delivery System and LOTUS Edge Valve System
Primary Outcome Measures
NameTimeMethod
Technical SuccessImmediately post-procedure (patient discharged from operative room)

Defined as successful vascular access, delivery, and deployment of the Lotus Valve; successful retrieval with the Lotus Next Generation delivery system; and correct positioning of a single Lotus Valve in the proper anatomical location (reported as percent of subjects implanted with a Lotus Valve). Reported as percent of subjects.

Secondary Outcome Measures
NameTimeMethod
Severe or moderate paravalvular aortic regurgitation as measured by echocardiography and assessed by an independent core laboratoryAt discharge from hospital or at 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure

Reported as percent of subjects

Mean aortic valve pressure gradient as measured by echocardiography and assessed by an independent core laboratoryAt discharge from hospital or at 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure

Reported as mean ± standard deviation; mmHg

Peak aortic valve pressure gradient as measured by echocardiography and assessed by an independent core laboratoryAt discharge from hospital or at 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure

Reported as mean ± standard deviation; mmHg

Successful retrieval of the study valve if retrieval is attemptedImmediately post-procedure (patient discharged from operative room)

Reported as percent of subjects

Mortality: all-cause, cardiovascular, and non-cardiovascularAt discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure

Reported as percent of subjects

Acute kidney injury based on the Acute Kidney Injury Network (AKIN) System Stage 3 (including renal replacement therapy) or Stage 2≤7 days post index procedure

Reported as percent of subjects

Repeat procedure for valve-related dysfunction (surgical or interventional therapy)At discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure

Reported as percent of subjects

Coronary obstruction≤72 hours post index procedure

Reported as percent of subjects

Ventricular septal perforation≤72 hours post index procedure

Reported as percent of subjects

Prosthetic aortic valve thrombosisAt discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure

Reported as percent of subjects

Mild, trace/trivial, or no paravalvular aortic regurgitation as measured by echocardiography and assessed by an independent core laboratoryAt discharge from hospital or at 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure

Reported as percent of subjects

Hospitalization for valve-related symptoms or worsening congestive heart failure (NYHA class III or IV)At discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure

Reported as percent of subjects

Mitral apparatus damage≤72 hours post index procedure

Reported as percent of subjects

Prosthetic aortic valve malpositioning, including valve migration, valve embolization, or ectopic valve deploymentAt discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure

Reported as percent of subjects

Transcatheter aortic valve (TAV)-in-TAV deploymentAt discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure

Reported as percent of subjects

Stroke: disabling and non-disablingAt discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure

Reported as percent of subjects

Successful repositioning of the study valve if repositioning is attemptedImmediately post-procedure (patient discharged from operative room)

Reported as percent of subjects

Peak aortic velocity as measured by echocardiography and assessed by an independent core laboratoryAt discharge from hospital or at 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure

Reported as mean ± standard deviation; m/sec

Major vascular complications majorAt discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure

Reported as percent of subjects

New permanent pacemaker implantation resulting from new or worsened conduction disturbancesAt discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure

Reported as percent of subjects

Cardiac tamponade≤72 hours post index procedure

Reported as percent of subjects

Prosthetic aortic valve endocarditisAt discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure

Reported as percent of subjects

Effective orifice area as measured by echocardiography and assessed by an independent core laboratoryAt discharge from hospital or at 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure

Reported as mean ± standard deviation; cm2

Myocardial infarction (MI): periprocedural (≤72 hours post index procedure) and spontaneous (>72 hours post index procedure)At discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure

Reported as percent of subjects

Bleeding: life-threatening (or disabling) and majorAt discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure

Reported as percent of subjects

New onset of atrial fibrillation or atrial flutterAt discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure

Reported as percent of subjects

Neurological status per modified Rankin Scale scoreAt discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure

Reported as percent of subjects

Neurological status per National Institutes of Health Stroke ScaleAt discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure

Reported as percent of subjects

Functional Improvement from baseline per NYHA functional classificationAt discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure

Reported as percent of subjects

Trial Locations

Locations (2)

Monash Heart

🇦🇺

Clayton, Victoria, Australia

Prince Charles Hospital

🇦🇺

Chermside, Queensland, Australia

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