Clinical trial NCT02854319: REpositionable Percutaneous Replacement of NatIve StEnotic Aortic Valve Through Implantation of LOTUS EDGE Valve System
Official title: REPRISE EDGE: REpositionable Percutaneous Replacement of NatIve StEnotic Aortic Valve Through Implantation of LOTUS EDGE Valve System - Evaluation of Performance and Safety
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Aortic Valve Stenosis
Lead sponsor: Boston Scientific Corporation
Sponsor class: INDUSTRY
First posted: 2016-08-03
Enrollment: 15
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The objective of the REPRISE EDGE study is to confirm the acute performance and safety of the LOTUS Edge™ Valve System when used with the Lotus™ or iSleeve™ Introducer Set for transcatheter aortic valve implantation (TAVI) 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 or Lotus Introducer Set are consistent with the results of the commercially approved 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).

Eligibility criteria: 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 and/or invasive hemodynamics.

   Note: In cases of low flow, low gradient aortic stenosis 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.
3. Subject has a documented aortic annulus size between ≥20 mm and ≤27 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:

   * 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 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 aortic or mitral valve.
6. Subject has \>3+ mitral regurgitation, \>3+ aortic regurgitation or \>3+ 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 new intra-cardiac vegetation or intraventricular or paravalvular thrombus requiring intervention.
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 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.

    Note: An alternative P2Y12 inhibitor may be prescribed if subject is allergic to or intolerant of clopidogrel
12. 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.
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 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).
21. Subject has arterial access that is not acceptable for the LOTUS Edge delivery system and its compatible Lotus or iSleeve Introducers as defined in the Directions For Use, or severe iliofemoral tortuosity or calcification that would prevent safe placement of either 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 does not have a permanent pacemaker but has a class I or II indication for pacemaker implantation (based on the latest available ESC guidelines).

Primary outcomes:
measure: Mean aortic valve pressure gradient
timeFrame: At discharge from hospital or at 7 days post-procedure (whichever comes first)
Secondary outcomes:
measure: Technical success
timeFrame: Immediately post-procedure (patient discharged from operative room)
measure: Effective orifice area
timeFrame: At discharge from hospital or at 7 days post-procedure (whichever comes first)
measure: Successful repositioning of the study valve if repositioning is attempted
timeFrame: Immediately post-procedure (patient discharged from operative room)
measure: Successful retrieval of the study valve if retrieval is attempted
timeFrame: Immediately post-procedure (patient discharged from operative room)
measure: Grade of paravalvular aortic regurgitation
timeFrame: At discharge from hospital or at 7 days post-procedure (whichever comes first)
Other outcomes:
measure: Mortality: all-cause, cardiovascular, and non-cardiovascular
timeFrame: At discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1 year post procedure
measure: Stroke: disabling and non-disabling
timeFrame: At discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1 year post procedure
measure: Myocardial infarction (MI): periprocedural (≤72 hours post index procedure) and spontaneous (>72 hours post index procedure)
timeFrame: At discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1 year post procedure
measure: Bleeding: life-threatening (or disabling) and major
timeFrame: At discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1 year post procedure
measure: Acute kidney injury based on the AKIN System Stage 3 (including renal replacement therapy) or Stage 2
timeFrame: At discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1 year post procedure
measure: Major vascular complication
timeFrame: At discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1 year post procedure
measure: Repeat procedure for valve-related dysfunction (surgical or interventional therapy)
timeFrame: At discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1 year post procedure
measure: Hospitalization for valve-related symptoms or worsening congestive heart failure (New York Hear Association [NYHA] class III or IV)
timeFrame: At discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1 year post procedure
measure: New permanent pacemaker implantation resulting from new or worsened conduction disturbances (including new left bundle branch block [LBBB] and third degree atrioventricular block)
timeFrame: At discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1 year post procedure
measure: New onset of atrial fibrillation or atrial flutter
timeFrame: At discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1 year post procedure
measure: Coronary obstruction
timeFrame: ≤72 hours post index procedure
measure: Ventricular septal perforation
timeFrame: ≤72 hours post index procedure
measure: Mitral apparatus damage
timeFrame: ≤72 hours post index procedure
measure: Cardiac tamponade
timeFrame: ≤72 hours post index procedure
measure: Prosthetic aortic valve malpositioning, including valve migration, valve embolization, or ectopic valve deployment
timeFrame: At discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1 year post procedure
measure: Transcatheter aortic valve (TAV)-in-TAV deployment
timeFrame: At discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1 year post procedure
measure: Prosthetic aortic valve thrombosis
timeFrame: At discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1 year post procedure
measure: Prosthetic aortic valve endocarditis
timeFrame: At discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1 year post procedure
measure: Prosthetic aortic valve performance: effective orifice area
timeFrame: 30 days, 6 months, and 1 year post procedure
measure: Prosthetic aortic valve performance: mean pressure gradient
timeFrame: 30 days, 6 months, and 1 year post procedure
measure: Prosthetic aortic valve performance: aortic valve regurgitation
timeFrame: At discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1 year post procedure
measure: Prosthetic aortic valve performance: peak gradient
timeFrame: At discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1 year post procedure
measure: Prosthetic aortic valve performance: peak velocity
timeFrame: At discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1 year post procedure
measure: Functional status as evaluated by New York Heart Association (NYHA) classification
timeFrame: At discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1 year post procedure
measure: Neurological status: National Institutes of Health Stroke Scale (NIHSS)
timeFrame: At discharge and 1 year
measure: Neurological status: Modified Rankin Scale (mRS)
timeFrame: At discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1 year post procedure
Locations:
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Toulouse
country: France
facility: Clinique Pasteur
city: Lund
country: Sweden
facility: Skåne University Hospital
Study officials:
affiliation: Skane University Hospital
name: Matthias Götberg, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: German Heart Centre München
name: Sabine Bleiziffer, MD
role: PRINCIPAL_INVESTIGATOR
References: