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

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02491255
Recruitment Status : Active, not recruiting
First Posted : July 8, 2015
Last Update Posted : August 12, 2019
Sponsor:
Information provided by (Responsible Party):
Boston Scientific Corporation

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

Condition or disease Intervention/treatment Phase
Aortic Stenosis Device: Lotus Valve System Not Applicable

Detailed Description:
A prospective, multicenter trial designed to confirm that the safety and effectiveness of the Lotus Valve System in the Japanese medical environment are consistent with the REPRISE III results for TAVR in symptomatic subjects who have calcific, severe native aortic stenosis and who are at extreme or high risk for surgical valve replacement.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 70 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: REPRISE Japan: Repositionable Percutaneous Replacement of Stenotic Aortic Valve Through Implantation of Lotus™ Valve System - Clinical Evaluation in Japan
Actual Study Start Date : June 22, 2015
Actual Primary Completion Date : January 30, 2017
Estimated Study Completion Date : December 30, 2021

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Primary Safety Endpoint: Composite of all-cause mortality, stroke, life-threatening and major bleeding events, stage 2 or 3 acute kidney injury, or major vascular complications [ Time Frame: 30 days following procedure ]
  2. Primary Effectiveness Endpoint: Composite of all-cause mortality, disabling stroke(adjudicated by an independent CEC), or moderate or greater paravalvular aortic regurgitation(based on independent core laboratory assessment) [ Time Frame: 6 month following procedure ]

Secondary Outcome Measures :
  1. Moderate or greater paravalvular aortic regurgitation (based on core lab assessment) [ Time Frame: 6 month following procedure ]

Other Outcome Measures:
  1. Successful deployment of the study valve [ Time Frame: at discharge or 7 days post-procedure (whichever comes first) ]
  2. Successful retrieval of the study valve if retrieval is attempted [ Time Frame: at discharge or 7 days post-procedure (whichever comes first) ]
  3. Successful repositioning of the study valve if repositioning is attempted [ Time Frame: at discharge or 7 days post-procedure (whichever comes first) ]
  4. Grade of aortic valve regurgitation: paravalvular, central, and combined [ Time Frame: at discharge or 7 days post-procedure (whichever comes first) ]
  5. Clinical procedural success [ Time Frame: 30 days post procedure ]
    Defined as implantation of the test device in the absence of death, disabling stroke, major vascular complications, and life-threatening or major bleeding

  6. 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 at 30 days (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 [ Time Frame: At discharge or 7 days post-procedure (whichever comes first) ]
    assessed by an independent core laboratory, including effective orifice area, mean and peak aortic gradients, peak aortic velocity, and grade of aortic regurgitation

  8. Additional indications of prosthetic aortic valve performance as measured by transthoracic echocardiography [ Time Frame: 30 days post procedure ]
    assessed by an independent core laboratory, including effective orifice area, mean and peak aortic gradients, peak aortic velocity, and grade of aortic regurgitation

  9. Additional indications of prosthetic aortic valve performance as measured by transthoracic echocardiography [ Time Frame: 6 months post procedure ]
    assessed by an independent core laboratory, including effective orifice area, mean and peak aortic gradients, peak aortic velocity, and grade of aortic regurgitation

  10. Additional indications of prosthetic aortic valve performance as measured by transthoracic echocardiography [ Time Frame: 1 year post procedure ]
    assessed by an independent core laboratory, including effective orifice area, mean and peak aortic gradients, peak aortic velocity, and grade of aortic regurgitation

  11. Additional indications of prosthetic aortic valve performance as measured by transthoracic echocardiography [ Time Frame: 2 years post procedure ]
    assessed by an independent core laboratory, including effective orifice area, mean and peak aortic gradients, peak aortic velocity, and grade of aortic regurgitation

  12. Additional indications of prosthetic aortic valve performance as measured by transthoracic echocardiography [ Time Frame: 3 years post procedure ]
    assessed by an independent core laboratory, including effective orifice area, mean and peak aortic gradients, peak aortic velocity, and grade of aortic regurgitation

  13. Additional indications of prosthetic aortic valve performance as measured by transthoracic echocardiography [ Time Frame: 4 years post procedure ]
    assessed by an independent core laboratory, including effective orifice area, mean and peak aortic gradients, peak aortic velocity, and grade of aortic regurgitation

  14. Additional indications of prosthetic aortic valve performance as measured by transthoracic echocardiography [ Time Frame: 5 years post procedure ]
    assessed by an independent core laboratory, including effective orifice area, mean and peak aortic gradients, peak aortic velocity, and grade of aortic regurgitation

  15. Health status as evaluated by Quality of Life questionnaires [ Time Frame: baseline, 1 and 6 months; and 1, 3, and 5 years ]
    SF-12 and Kansas City Cardiomyopathy

  16. Mortality: all-cause, cardiovascular, and non-cardiovascular [ Time Frame: At discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1, 2, 3, 4, and 5 years post procedure ]
  17. Stroke: disabling and non-disabling [ Time Frame: At discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1, 2, 3, 4, and 5 years post procedure ]
  18. Myocardial infarction (MI): periprocedural (≤72 hours post index procedure) and spontaneous (>72 hours post index procedure) [ Time Frame: At discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1, 2, 3, 4, and 5 years post procedure ]
  19. Bleeding: life-threatening (or disabling) and major [ Time Frame: At discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1, 2, 3, 4, and 5 years post procedure ]
  20. Acute kidney injury based on the AKIN System Stage 3 (including renal replacement therapy) or Stage 2 [ Time Frame: ≤7 days post index procedure ]
  21. Major vascular complication [ Time Frame: At discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1, 2, 3, 4, and 5 years post procedure ]
  22. Repeat procedure for valve-related dysfunction (surgical or interventional therapy) [ Time Frame: At discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1, 2, 3, 4, and 5 years post procedure ]
  23. Hospitalization for valve-related symptoms or worsening congestive heart failure (New York Hear Association [NYHA] class III or IV) [ Time Frame: At discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1, 2, 3, 4, and 5 years post procedure ]
  24. New permanent pacemaker implantation resulting from new or worsened conduction disturbances [ Time Frame: At discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1, 2, 3, 4, and 5 years post procedure ]
  25. New onset of atrial fibrillation or atrial flutter [ Time Frame: Within the index hospitalization ]
  26. Coronary obstruction [ Time Frame: ≤72 hours post index procedure ]
  27. Ventricular septal perforation [ Time Frame: ≤72 hours post index procedure ]
  28. Mitral apparatus damage [ Time Frame: ≤72 hours post index procedure ]
  29. Cardiac tamponade [ Time Frame: ≤72 hours post index procedure ]
  30. Prosthetic aortic valve malpositioning, including valve migration, valve embolization, or ectopic valve deployment [ Time Frame: At discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1, 2, 3, 4, and 5 years post index procedure ]
  31. Transcatheter aortic valve (TAV)-in-TAV deployment [ Time Frame: At discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1, 2, 3, 4, and 5 years post index procedure ]
  32. Prosthetic aortic valve thrombosis [ Time Frame: At discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1, 2, 3, 4, and 5 years post index procedure ]
  33. Prosthetic aortic valve endocarditis [ Time Frame: At discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 1, 2, 3, 4, and 5 years post index procedure ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

IC1. Subject has documented calcific, severe native aortic stenosis with an initial 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.

IC2. Subject has a documented aortic annulus size of ≥18 mm and ≤27 mm based on the Center's assessment of pre-procedure diagnostic imaging (and confirmed by the Case Review Committee [CRC]) and is deemed treatable with an available size of the test device

IC3. Subject has symptomatic aortic valve stenosis with NYHA Functional Class ≥ II

IC4. 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, FEV1 <50% of predicted, 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 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)

IC5. Heart team (which must include a cardiac interventionalist and an experienced cardiac surgeon) assessment that the subject is likely to benefit from valve replacement.

IC6. Subject (or legal representative) understands the study requirements and the treatment procedures, and provides written informed consent.

IC7. 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.

IC8. Subject must be at least 20 years old.

IC9. For subjects not suitable for iliofemoral access (because of caliber of the iliofemoral vessels, severe tortuosity or other factors preventing safe iliofemoral access), trans-aortic access is deemed appropriate by the heart team and confirmed by the CRC. This inclusion criterion is only applicable to the TAo substudy and the 21mm substudy if the transaortic approach is used.

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.

EC1. Subject has a congenital unicuspid or bicuspid aortic valve.

EC2. Subject has had an acute myocardial infarction within 30 days prior to 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).

EC3. Subject has had a cerebrovascular accident or transient ischemic attack within the past 6 months prior to study enrollment.

EC4. Subject has end-stage renal disease or has eGFR <20. Note: eGFR(ml/min/1.73m2)=194×Cr-1.094×Age-0.287×(If female×0.739)

EC5. Subject has a pre-existing prosthetic aortic or mitral valve.

EC6. Subject has severe aortic, tricuspid, or mitral regurgitation.

EC7. Subject has a need for emergency surgery for any reason.

EC8. Subject has a history of endocarditis within 6 months of index procedure or evidence of an active systemic infection or sepsis.

EC9. Subject has echocardiographic evidence of new intra-cardiac vegetation or intraventricular or paravalvular thrombus requiring intervention.

EC10. 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.

EC11. 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 P2Y12 inhibitor (clopidogrel or ticlopidine, but prasugrel is not allowed).

EC12. Subject 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.

EC13. 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.

EC14. 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.

EC15. Subject has hypertrophic obstructive cardiomyopathy.

EC16. 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).

EC17. Subject has untreated coronary artery disease, which in the opinion of the treating physician is clinically significant and requires revascularization.

EC18. Subject has severe left ventricular dysfunction with ejection fraction <20%.

EC19. Subject is in cardiogenic shock or has hemodynamic instability requiring inotropic support or mechanical support devices.

EC20. 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). This exclusion criterion is only applicable to the TF study and the 21mm substudy if the transfemoral or transiliac approach is used.

EC21. Subject has thick (>5 mm) protruding or ulcerated atheroma in the aortic arch. This exclusion criterion is only applicable to the TF study and the 21mm substudy if the transfemoral or transiliac approach is used.

EC22. Subject has arterial access that is not acceptable for the test device delivery systems as defined in the device Instructions For Use.

EC23. Subject has current problems with substance abuse (e.g., alcohol, etc.).

EC24. Subject is participating in another investigational drug or device study that has not reached its primary endpoint.

EC25. 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.

EC26. Subject has severe incapacitating dementia.

EC27. Subject is a woman who is pregnant, nursing (a pregnancy test must be performed in women of potential child-bearing) or wishes to be pregnant


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): NCT02491255


Locations
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Japan
Shonankamakura General Hospital
Kamakura, Kanagawa, Japan, 247-8533
Kurashiki Central Hospital
Kurashiki, Okayama, Japan, 710-8602
Osaka University Hospital
Suita, Osaka, Japan, 565-0871
Sakakibara Heart Institute
Fuchu, Tokyo, Japan, 183-0003
Keio University Hospital
Shinjuku, Tokyo, Japan, 160-8582
Sponsors and Collaborators
Boston Scientific Corporation
Investigators
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Principal Investigator: Yoshiki Sawa Osaka University Hospital
Principal Investigator: Shigeru Saito Shonankamakura General Hospital

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Responsible Party: Boston Scientific Corporation
ClinicalTrials.gov Identifier: NCT02491255     History of Changes
Other Study ID Numbers: S6002
First Posted: July 8, 2015    Key Record Dates
Last Update Posted: August 12, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Aortic Valve Stenosis
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases
Ventricular Outflow Obstruction