Performance and Safety of the Lotus™ Valve With a FLEXible Delivery System

REPRISE II FLEX: Repositionable Percutaneous Replacement of Stenotic Aortic Valve Through Implantation of LotuS™ ValvE With a FLEXible Delivery System - Confirmation of Performance and Safety

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

Study Overview

• Status: Completed
• Conditions: Aortic Stenosis
• Intervention / Treatment: Device: Transcatheter aortic valve replacement

Detailed Description

This clinical study is a prospective, single-arm study designed to confirm that the acute performance and safety of the Lotus Valve Flex System for TAVR are consistent with the results of the Lotus Valve System 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).

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Chermside, Queensland, Australia, 4032
      • Prince Charles Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Heart

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 mm based on pre-procedure diagnostic imaging
• 4. 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:

  1. Society of Thoracic Surgeons (STS) score ≥8%, AND/OR
  2. 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 CK-MB elevation and/or troponin 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 µmol/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 requires chronic anticoagulation therapy (warfarin) and cannot tolerate concomitant therapy with either aspirin or clopidogrel.

    Note: Subjects who require chronic anticoagulation must be able to be treated additionally with either aspirin or clopidogrel. An alternative P2Y12 inhibitor may be prescribed if subject is allergic to or intolerant of 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, tantalum, 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 (including balloon aortic valvuloplasty) within 30 days prior to the index procedure (except for pacemaker implantation which is 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lotus Valve Flex System; Transcatheter aortic valve replacement (TAVR) with Lotus Valve FLEX System	Device: Transcatheter aortic valve replacement; TAVR with Lotus Valve Flex System

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Technical success	defined as successful vascular access, delivery and deployment of the Lotus Valve and successful retrieval of the delivery system; and correct positioning of a single Lotus Valve in the proper anatomical location; reported as percent of subjects.	immediately post-procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean aortic valve pressure gradient and effective orifice area	as measured by echocardiography and assessed by an independent core laboratory	at discharge or 7 days post-procedure (whichever comes first)
Device performance	defined as successful repositioning of the Lotus Valve if repositioning is attempted; and successful retrieval of the Lotus Valve if retrieval is attempted; and grade of paravalvular aortic regurgitation, as measured by echocardiography and assessed by an independent core laboratory	at discharge or 7 days post-procedure (whichever comes first)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality: all-cause, cardiovascular, and non-cardiovascular		at discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1, 2, 3, 4, and 5 years post procedure
Stroke: disabling and non-disabling		at discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1, 2, 3, 4, and 5 years post procedure
Composite of all-cause mortality and disabling stroke		at discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1, 2, 3, 4, and 5 years post procedure
Bleeding: life-threatening (or disabling) and major		at discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1, 2, 3, 4, and 5 years post procedure
Myocardial infarction (MI)		periprocedural (≤72 hours post index procedure) and spontaneous (>72 hours post index procedure)
Acute kidney injury: based on the AKIN System Stage 3 (including renal replacement therapy) or Stage 2		≤7 days post index procedure
Major vascular complication		at discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1, 2, 3, 4, and 5 years post procedure
Repeat procedure for valve-related dysfunction (surgical or interventional therapy)		at discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1, 2, 3, 4, and 5 years post procedure
Hospitalization for valve-related symptoms or worsening congestive heart failure (NYHA class III or IV)		at discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1, 2, 3, 4, and 5 years post procedure
New permanent pacemaker implantation resulting from new or worsened conduction disturbances (including new left bundle branch block [LBBB] and third degree atrioventricular block)		at discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1, 2, 3, 4, and 5 years post procedure
New onset of atrial fibrillation or atrial flutter		at discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1, 2, 3, 4, and 5 years post procedure
Coronary obstruction		≤7 days post procedure
Ventricular septal perforation, reported as percent of subjects		≤7 days post procedure
Mitral apparatus damage, reported as percent of subjects		≤7 days post procedure
Cardiac tamponade, reported as percent of subjects		≤7 days post procedure
Prosthetic aortic valve malposition, including valve migration, valve embolization, ectopic valve deployment, or transcatheter aortic valve (TAV)-in-TAV deployment		at discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1, 2, 3, 4, and 5 years post procedure
Prosthetic aortic valve thrombosis		at discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1, 2, 3, 4, and 5 years post procedure
Prosthetic aortic valve endocarditis		at discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1, 2, 3, 4, and 5 years post procedure
Prosthetic aortic valve performance	as measured by transthoracic echocardiography (TTE) and assessed by an independent core laboratory, including effective orifice area, mean and peak aortic gradients, peak aortic velocity, and grade of aortic regurgitation	at discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1, 2, 3, 4, and 5 years post procedure
Functional status	as evaluated by the New York Heart Association (NYHA) classification	at discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1, 2, 3, 4, and 5 years post procedure
Neurological status	as determined by the National Institutes of Health Stroke Scale (NIHSS)	at discharge and 1 year
Neurological status	as determined by the Modified Rankin Scale (mRS)	at discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1, 2, 3, 4, and 5 years post procedure

Collaborators and Investigators

• Sponsor: Boston Scientific Corporation
• Investigators: Principal Investigator: Ian T Meredith, MD, PhD, Monash

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2013
• Primary Completion (Actual): December 10, 2013
• Study Completion (Actual): December 10, 2018

Study Registration Dates

• First Submitted: February 1, 2017
• First Submitted That Met QC Criteria: February 2, 2017
• First Posted (Estimate): February 6, 2017

Study Record Updates

• Last Update Posted (Actual): July 5, 2019
• Last Update Submitted That Met QC Criteria: July 2, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis
• Other Study ID Numbers: S2321

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No