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Safety and Efficacy Study of Lotus Valve for Transcatheter Aortic Valve Replacement (REPRISE III)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02202434
Recruitment Status : Recruiting
First Posted : July 29, 2014
Results First Posted : July 30, 2019
Last Update Posted : July 30, 2019
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Aortic Stenosis Device: Lotus Valve System Device: CoreValve/Evolut R Transcatheter Aortic Valve Replacement System Device: LOTUS Edge Valve System Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1475 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: REPRISE III: Repositionable Percutaneous Replacement of Stenotic Aortic Valve Through Implantation of Lotus™ Valve System - Randomized Clinical Evaluation
Actual Study Start Date : September 22, 2014
Actual Primary Completion Date : March 8, 2017
Estimated Study Completion Date : February 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Lotus Valve System - Randomized
Transcatheter aortic valve replacement (TAVR) with Lotus Valve System
Device: Lotus Valve System
Procedure: Transcatheter aortic valve replacement (TAVR)

Active Comparator: CoreValve TAVR System - Randomized
Transcatheter aortic valve replacement (TAVR) with CoreValve/Evolut R Transcatheter Aortic Valve Replacement System
Device: CoreValve/Evolut R Transcatheter Aortic Valve Replacement System
Procedure: Transcatheter aortic valve replacement (TAVR)

Experimental: LOTUS Edge Valve System - Single-arm 29mm Roll-in Cohort
Transcatheter aortic valve replacement (TAVR) with 29mm LOTUS Edge Valve System
Device: LOTUS Edge Valve System
Procedure: Transcatheter aortic valve replacement (TAVR)

Experimental: Lotus Valve Sytem - Single-arm 21mm Cohort
Transcatheter aortic valve replacement (TAVR) with 21mm Lotus Valve System
Device: Lotus Valve System
Procedure: Transcatheter aortic valve replacement (TAVR)

Experimental: Lotus Valve System - Single-arm Continued Access Cohort
Transcatheter aortic valve replacement (TAVR) with Lotus Valve System
Device: Lotus Valve System
Procedure: Transcatheter aortic valve replacement (TAVR)

Experimental: Lotus Valve System - Single-arm Roll-in Cohort
Transcatheter aortic valve replacement (TAVR) with Lotus Valve System
Device: Lotus Valve System
Procedure: Transcatheter aortic valve replacement (TAVR)

Experimental: LOTUS Edge Valve System - Single-arm 29mm Registry Cohort
Transcatheter aortic valve replacement (TAVR) with 29mm LOTUS Edge Valve System
Device: LOTUS Edge Valve System
Procedure: Transcatheter aortic valve replacement (TAVR)

Experimental: LOTUS Edge Valve System - Single-arm Edge Nested Registry

Transcatheter aortic valve replacement (TAVR) with 23mm, 25mm and 27mm LOTUS Edge Valve System.

This arm is recruiting.

Device: LOTUS Edge Valve System
Procedure: Transcatheter aortic valve replacement (TAVR)




Primary Outcome Measures :
  1. Percentage of Participants With Events Included in the Primary Safety Endpoint [ Time Frame: 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

  2. Percentage of Participants With Events Included in the Primary Effectiveness Endpoint [ Time Frame: 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 :
  1. Percentage of Participants With Moderate or Greater Paravalvular Aortic Regurgitation [ Time Frame: 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).


Other Outcome Measures:
  1. Percentage of Participants With Successful Deployment of the Study Valve [ Time Frame: at discharge or 7 days post-procedure (whichever comes first) ]
    Successful deployment of the study valve

  2. Percentage of Participants With Successful Retrieval of the Study Valve if Retrieval is Attempted [ Time Frame: at discharge or 7 days post-procedure (whichever comes first) ]
    Successful retrieval of the study valve if retrieval is attempted

  3. Percentage of Participants With Successful Repositioning of the Study Valve if Repositioning is Attempted [ Time Frame: at discharge or 7 days post-procedure (whichever comes first) ]
    Successful repositioning of the study valve if repositioning is attempted

  4. Percentage of Participants With Each Grade of Aortic Valve Regurgitation in Each Location: Paravalvular, Central, and Combined [ Time Frame: at discharge or 7 days post-procedure (whichever comes first) ]

    Grade of aortic valve regurgitation: paravalvular, central, and combined. An Independent echocardiographic core lab assessment was performed using the Unifying 5-Class Grading Scheme for Aortic Regurgitation for the locations paravalvular, central and combined.

    The grading scheme has a range from Trace to Severe. A grade of Trace is the least clinically significant (better outcome) and a grade of Severe is the most clinically significant (worse outcome).


  5. Percentage of Participants With Clinical Procedural Success [ Time Frame: 30 days post procedure ]
    Defined as implantation of the study device in the absence of death, disabling stroke, major vascular complications, and life-threatening or major bleeding

  6. Percentage of Participants With Procedural Success [ Time Frame: 30 days post procedure ]
    Defined as absence of procedural mortality, correct positioning of a single transcatheter valve into the proper anatomical location , intended performance of the study device (effective orifice area [EOA] >0.9 cm2 for body surface area (BSA) <1.6 m2 and EOA >1.1 cm2 for BSA ≥1.6 m2 plus either a mean aortic valve gradient <20 mm Hg or a peak velocity <3m/sec, and no moderate or severe prosthetic valve aortic regurgitation) plus no serious adverse events

  7. Additional Indications of Prosthetic Aortic Valve Performance as Measured by Transthoracic Echocardiography 1 [ Time Frame: assessed at discharge, 30 days, 6 months, and 1, 2, 3, 4, and 5 years post index procedure, at discharge, 30 days, 6 months, and 1 year post index procedure reported. ]
    Assessed by an independent core laboratory, including effective orifice area, mean and peak aortic gradients, and peak aortic velocity

  8. Additional Indications of Prosthetic Aortic Valve Performance as Measured by Transthoracic Echocardiography 2 [ Time Frame: assessed at discharge, 30 days, 6 months, and 1, 2, 3, 4, and 5 years post index procedure, at discharge, 30 days, 6 months, and 1 year post index procedure reported. ]
    Assessed by an independent core laboratory - mean and peak aortic gradients

  9. Additional Indications of Prosthetic Aortic Valve Performance as Measured by Transthoracic Echocardiography 3 [ Time Frame: assessed at discharge, 30 days, 6 months, and 1, 2, 3, 4, and 5 years post index procedure, at discharge, 30 days, 6 months, and 1 year post index procedure reported. ]
    Assessed by an independent core laboratory - peak aortic velocity

  10. Percentage of Participants With Additional Indications of Prosthetic Aortic Valve Performance as Measured by Transthoracic Echocardiography 4 [ Time Frame: assessed at discharge, 30 days, 6 months, and 1, 2, 3, 4, and 5 years post index procedure, at discharge, 30 days, 6 months, and 1 year post index procedure reported. ]

    Grade of aortic valve regurgitation: paravalvular, central, and combined. An Independent echocardiographic core lab assessment was performed using the Unifying 5-Class Grading Scheme for Aortic Regurgitation for the locations paravalvular, central and combined.

    The grading scheme has a range from Trace to Severe. A grade of Trace is the least clinically significant (better outcome) and a grade of Severe is the most clinically significant (worse outcome).


  11. Health Status as Evaluated by Quality of Life Questionnaires [ Time Frame: Assessed at Baseline, 1 and 6 months; and 1, 3, and 5 years, at Baseline, 1 and 6 months and 1 Year reported ]

    SF-12 and Kansas City Cardiomyopathy - Baseline scores and changes from Baseline at 30 days, 6 months and 1 year

    • SF-12 Item Short Form Health Survey (SF-12): Measures functional health and well-being. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.
    • Kansas City Cardiomyopathy Questionnaire (KCCQ): Quantifies physical function, symptoms, social function, self-efficacy and knowledge, and quality of life.

    Scores are transformed to a range of 0-100, in which higher scores reflect better health status.


  12. Percentage of Participants With Mortality [ Time Frame: assessed at discharge, 30 days, 6 months, and 1, 2, 3, 4, and 5 years post index procedure, at discharge, 30 days, 6 months, and 1 year post index procedure reported. ]
    All-cause, Cardiovascular, and Non-cardiovascular

  13. Percentage of Participants With Stroke [ Time Frame: assessed at discharge, 30 days, 6 months, and 1, 2, 3, 4, and 5 years post index procedure, at discharge, 30 days, 6 months, and 1 year post index procedure reported. ]
    Disabling Stroke and Non-disabling Stroke

  14. Percentage of Participants With Myocardial Infarction (MI) [ Time Frame: assessed at discharge, 30 days, 6 months, and 1, 2, 3, 4, and 5 years post index procedure, at discharge, 30 days, 6 months, and 1 year post index procedure reported. ]
    Periprocedural (≤72 hours post index procedure) and spontaneous (>72 hours post index procedure)

  15. Percentage of Participants With Bleeding [ Time Frame: assessed at discharge, 30 days, 6 months, and 1, 2, 3, 4, and 5 years post index procedure, at discharge, 30 days, 6 months, and 1 year post index procedure reported. ]

    Life-threatening (or disabling) and major (defined below)

    Life-threatening or Disabling Bleeding

    • Fatal bleeding (Bleeding Academic Research Consortium [BARC] type 5124,125)
    • Bleeding in a critical organ, such as intracranial, intraspinal, intraocular, or pericardial necessitating pericardiocentesis, or intramuscular with compartment syndrome (BARC type 3b and 3c)
    • Bleeding causing hypovolemic shock or severe hypotension requiring vasopressors or surgery (BARC type 3b)
    • Overt source of bleeding with drop in hemoglobin of ≥5 g/dL or whole blood or packed red blood cells (RBC) transfusion ≥4 units (BARC type 3b)

    Major Bleeding (BARC type 3a)

    • Overt bleeding either associated with a drop in the hemoglobin level of at least 3.0g/dL or requiring transfusion of 2 or 3 units of whole blood/RBC, or causing hospitalization or permanent injury, or requiring surgery AND does not meet criteria of life-threatening or disabling bleeding

  16. Percentage of Participants With Acute Kidney Injury [ Time Frame: ≤7 days post index procedure ]

    Acute kidney injury based on the AKIN System Stage 3 (including renal replacement therapy) or Stage 2

    Change in serum creatinine (up to 7 days) compared to baseline:

    • Stage 1: Increase in serum creatinine to 150-199% (1.5-1.99 × increase compared with baseline) OR increase of ≥0.3 mg/dl (≥26.4 mmol/L)
    • Stage 2: Increase in serum creatinine to 200-299% (2.0-2.99 × increase compared with baseline)
    • Stage 3: Increase in serum creatinine to ≥300% (>3 × increase compared with baseline) OR serum creatinine of ≥4.0 mg/dL (≥354 mmol/L) with an acute increase of at least 0.5 mg/dL (44 mmol/L)

    -OR-

    Based on urine output (up to 7 days):

    • Stage 1: <0.5 ml/kg per hour for >6 but <12 hours
    • Stage 2: <0.5 ml/kg per hour for >12 but <24 hours
    • Stage 3: <0.3 ml/kg per hour for ≥24 hours or anuria for ≥12 hours

    Note 1: Subjects receiving renal replacement therapy are considered to meet Stage 3 criteria irrespective of other criteria.


  17. Percentage of Participants With Major Vascular Complication [ Time Frame: assessed at discharge, 30 days, 6 months, and 1, 2, 3, 4, and 5 years post index procedure, at discharge, 30 days, 6 months, and 1 year post index procedure reported. ]
    Major vascular complication - including access site related and non access site related

  18. Percentage of Participants With Repeat Procedure for Valve-related Dysfunction [ Time Frame: assessed at discharge, 30 days, 6 months, and 1, 2, 3, 4, and 5 years post index procedure, at discharge, 30 days, 6 months, and 1 year post index procedure reported. ]
    Repeat procedure for valve-related dysfunction (surgical or interventional therapy)

  19. Percentage of Participants With Hospitalization for Valve-related Symptoms or Worsening Congestive Heart Failure [ Time Frame: assessed at discharge, 30 days, 6 months, and 1, 2, 3, 4, and 5 years post index procedure, at discharge, 30 days, 6 months, and 1 year post index procedure reported. ]
    Hospitalization for valve-related symptoms or worsening congestive heart failure (New York Hear Association [NYHA] class III or IV)

  20. Percentage of Participants With New Permanent Pacemaker Implantation [ Time Frame: assessed at discharge, 30 days, 6 months, and 1, 2, 3, 4, and 5 years post index procedure, at discharge, 30 days, 6 months, and 1 year post index procedure reported. ]
    New permanent pacemaker implantation resulting from new or worsened conduction disturbances

  21. Percentage of Participants With New Onset of Atrial Fibrillation or Atrial Flutter [ Time Frame: assessed at discharge, 30 days, 6 months, and 1, 2, 3, 4, and 5 years post index procedure, at discharge, 30 days, 6 months, and 1 year post index procedure reported. ]
    New onset of atrial fibrillation or atrial flutter

  22. Percentage of Participants With Coronary Obstruction [ Time Frame: ≤72 hours post index procedure ]
    Coronary obstruction

  23. Percentage of Participants With Ventricular Septal Perforation [ Time Frame: ≤72 hours post index procedure ]
    Ventricular septal perforation

  24. Percentage of Participants With Mitral Apparatus Damage [ Time Frame: ≤72 hours post index procedure ]
    Mitral apparatus damage

  25. Percentage of Participants With Cardiac Tamponade [ Time Frame: ≤72 hours post index procedure ]
    Cardiac tamponade

  26. Percentage of Participants With Prosthetic Aortic Valve Malpositioning [ Time Frame: assessed at discharge, 30 days, 6 months, and 1, 2, 3, 4, and 5 years post index procedure, at discharge, 30 days, 6 months, and 1 year post index procedure reported. ]
    Prosthetic aortic valve malpositioning, including valve migration, valve embolization, or ectopic valve deployment

  27. Percentage of Participants With Prosthetic Aortic Valve Thrombosis [ Time Frame: assessed at discharge, 30 days, 6 months, and 1, 2, 3, 4, and 5 years post index procedure, at discharge, 30 days, 6 months, and 1 year post index procedure reported. ]
    Prosthetic aortic valve thrombosis

  28. Percentage of Participants With Prosthetic Aortic Valve Endocarditis [ Time Frame: assessed at discharge, 30 days, 6 months, and 1, 2, 3, 4, and 5 years post index procedure, at discharge, 30 days, 6 months, and 1 year post index procedure reported. ]
    Prosthetic aortic valve endocarditis



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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
  2. 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.
  3. Subject has symptomatic aortic valve stenosis with New York Heart Association (NYHA) Functional Class ≥ II
  4. 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)
  5. Heart team (which must include a cardiac interventionalist and an experienced cardiac surgeon) assessment that the subject is likely to benefit from valve replacement.
  6. Subject (or legal representative) understands the study requirements and the treatment procedures, and provides written informed consent.
  7. 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:

  1. Subject has a congenital unicuspid or bicuspid aortic valve.
  2. 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).
  3. Subject has had a cerebrovascular accident or transient ischemic attack within the past 6 months prior to study enrollment.
  4. Subject has end-stage renal disease or has glomerular filtration rate (GFR) <20 (based on Cockcroft-Gault formula).
  5. Subject has a pre-existing prosthetic aortic or mitral valve.
  6. Subject has severe (4+) aortic, tricuspid, or mitral regurgitation.
  7. Subject has a need for emergency surgery for any reason.
  8. Subject has a history of endocarditis within 6 months of index procedure or evidence of an active systemic infection or sepsis.
  9. Subject has echocardiographic evidence of new intra-cardiac mass, vegetation or intraventricular or paravalvular thrombus requiring intervention.
  10. 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.
  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.
  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 P2Y12 inhibitors, heparin, nickel, tantalum, titanium, or polyurethanes.
  14. 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.
  15. Subject has hypertrophic obstructive cardiomyopathy.
  16. 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).
  17. Subject has untreated coronary artery disease, which in the opinion of the treating physician is clinically significant and requires revascularization.
  18. Subject has severe left ventricular dysfunction with ejection fraction <20%.
  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 thick (>5 mm) protruding or ulcerated atheroma in the aortic arch
  22. Subject has arterial access that is not acceptable for the test and control device delivery systems as defined in the device Instructions For Use.
  23. Subject has current problems with substance abuse (e.g., alcohol, etc.).
  24. Subject is participating in another investigational drug or device study that has not reached its primary endpoint.
  25. 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.
  26. Subject has severe incapacitating dementia.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02202434


Contacts
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Contact: Amy Maurer, MA 508-683-6647 amy.maurer@bsci.com

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Sponsors and Collaborators
Boston Scientific Corporation
Investigators
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Principal Investigator: David Rizik, MD Scottsdale Healthcare - Shea
Principal Investigator: Michael J Reardon, MD The Methodist Hospital System
  Study Documents (Full-Text)

Documents provided by Boston Scientific Corporation:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Boston Scientific Corporation
ClinicalTrials.gov Identifier: NCT02202434     History of Changes
Other Study ID Numbers: S2282
First Posted: July 29, 2014    Key Record Dates
Results First Posted: July 30, 2019
Last Update Posted: July 30, 2019
Last Verified: March 2019
Additional relevant MeSH terms:
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Aortic Valve Stenosis
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases
Ventricular Outflow Obstruction