Safety and Efficacy Study of Lotus Valve for Transcatheter Aortic Valve Replacement

Aortic Stenosis Clinical Trial

— REPRISE III  

Official title:

REPRISE III: Repositionable Percutaneous Replacement of Stenotic Aortic Valve Through Implantation of Lotus™ Valve System - Randomized Clinical Evaluation

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02202434
• Other study ID #: S2282
• Status: Terminated
• Phase: N/A
• Start date: September 22, 2014
• Est. completion date: May 21, 2021

Study information

• Verified date: December 2021
• Source: Boston Scientific Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1425
• Est. completion date: May 21, 2021
• Est. primary completion date: March 8, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Aortic Stenosis
• Aortic Valve Stenosis

Intervention

Device:
• Lotus Valve System
Procedure: Transcatheter aortic valve replacement (TAVR)
• CoreValve/Evolut R Transcatheter Aortic Valve Replacement System
Procedure: Transcatheter aortic valve replacement (TAVR)
• LOTUS Edge Valve System
Procedure: Transcatheter aortic valve replacement (TAVR)

Locations

Country	Name	City	State
Australia	The Prince Charles Hospital	Chermside	Queensland
Australia	Monash Medical Centre	Clayton	Victoria
Canada	McGill University Health Centre, Royal Victoria Hospital	Montreal	Quebec
Canada	Providence Health - St. Paul's Hospital	Vancouver	British Columbia
France	Centre Hôpital Universitaire Rangueil	Toulouse
France	Clinique Pasteur	Toulouse	Midi-Pyrenees
Germany	Universitares Herzzentrum UKE (Hamburg)	Hamburg
Germany	Herzzentrum Universität Leipzig	Leipzig	Saxony
Netherlands	Erasmus MC - University Medical Center Rotterdam	Rotterdam
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University Hospital	Atlanta	Georgia
United States	Piedmont Hospital	Atlanta	Georgia
United States	Union Memorial Hospital	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Kaleida Health	Buffalo	New York
United States	Lindner Center for Research and Education at The Christ Hospital	Cincinnati	Ohio
United States	Morton Plant Mease Healthcare System	Clearwater	Florida
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Ohio Health Research and Innovation Institute - Riverside Methodist Hospital	Columbus	Ohio
United States	Ohio State University Medical Center	Columbus	Ohio
United States	Baylor Heart and Vascular Hospital	Dallas	Texas
United States	Medical City Dallas Hospital	Dallas	Texas
United States	Delray Medical Center	Delray Beach	Florida
United States	Duke University Medical Center	Durham	North Carolina
United States	Evanston Hospital	Evanston	Illinois
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Methodist DeBakey Heart & Vascular Center	Houston	Texas
United States	St. Vincent's Hospital	Indianapolis	Indiana
United States	University of Kansas Hospital	Kansas City	Kansas
United States	Scripps Clinic	La Jolla	California
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	North Shore University Hospital	Manhasset	New York
United States	Baptist Cardiac and Vascular Institute	Miami	Florida
United States	University of Miami Hospital	Miami	Florida
United States	Aurora St. Luke's Medical Center	Milwaukee	Wisconsin
United States	Abbott Northwestern Hospital - Minneapolis Heart Institute	Minneapolis	Minnesota
United States	University of Minnesota Medical Center	Minneapolis	Minnesota
United States	Morristown Memorial Hospital	Morristown	New Jersey
United States	Columbia University Medical Center	New York	New York
United States	Veteran's Administration Palo Alto Medical Center	Palo Alto	California
United States	Cardiac & Vascular Rearch Center of Northern Michigan - Northern Michigan Hospital	Petoskey	Michigan
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Banner Good Samaritan	Phoenix	Arizona
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Providence St. Vincent Medical Center	Portland	Oregon
United States	NC Heart and Vascular Research - Rex Hospital	Raleigh	North Carolina
United States	Mayo Clinic	Rochester	Minnesota
United States	William Beaumont Hospital	Royal Oak	Michigan
United States	University of California at Davis Medical Center	Sacramento	California
United States	Washington University School of Medicine - Barnes Jewish Medical Center	Saint Louis	Missouri
United States	Methodist Heart Hospital	San Antonio	Texas
United States	Scottsdale Healthcare - Shea	Scottsdale	Arizona
United States	Swedish Medical Center	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	St. John's Hospital - Prairie Cardiovascular Consultants	Springfield	Illinois
United States	Stanford University Medical Center	Stanford	California
United States	Washington Hospital Center	Washington	District of Columbia
United States	Wake Forest University School of Medicine	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Boston Scientific Corporation

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Germany,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percentage of Participants With Successful Deployment of the Study Valve	Successful deployment of the study valve	at discharge or 7 days post-procedure (whichever comes first)
Other	Percentage of Participants With Successful Retrieval of the Study Valve if Retrieval is Attempted	Successful retrieval of the study valve if retrieval is attempted	at discharge or 7 days post-procedure (whichever comes first)
Other	Percentage of Participants With Successful Repositioning of the Study Valve if Repositioning is Attempted	Successful repositioning of the study valve if repositioning is attempted	at discharge or 7 days post-procedure (whichever comes first)
Other	Percentage of Participants With Each Grade of Aortic Valve Regurgitation in Each Location: Paravalvular, Central, and Combined	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).	at discharge or 7 days post-procedure (whichever comes first)
Other	Percentage of Participants With Clinical Procedural Success	Defined as implantation of the study device in the absence of death, disabling stroke, major vascular complications, and life-threatening or major bleeding	30 days post procedure
Other	Percentage of Participants With Procedural Success	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	30 days post procedure
Other	Additional Indications of Prosthetic Aortic Valve Performance as Measured by Transthoracic Echocardiography 1	Assessed by an independent core laboratory, including effective orifice area, mean and peak aortic gradients, and peak aortic velocity	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.
Other	Additional Indications of Prosthetic Aortic Valve Performance as Measured by Transthoracic Echocardiography 2	Assessed by an independent core laboratory - mean and peak aortic gradients	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.
Other	Additional Indications of Prosthetic Aortic Valve Performance as Measured by Transthoracic Echocardiography 3	Assessed by an independent core laboratory - peak aortic velocity	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.
Other	Percentage of Participants With Additional Indications of Prosthetic Aortic Valve Performance as Measured by Transthoracic Echocardiography 4	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).	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.
Other	Health Status as Evaluated by Quality of Life Questionnaires	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.	Assessed at Baseline, 1 and 6 months; and 1, 3, and 5 years, at Baseline, 1 and 6 months and 1 Year reported
Other	Percentage of Participants With Mortality	All-cause, Cardiovascular, and Non-cardiovascular	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.
Other	Percentage of Participants With Stroke	Disabling Stroke and Non-disabling Stroke	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.
Other	Percentage of Participants With Myocardial Infarction (MI)	Periprocedural (=72 hours post index procedure) and spontaneous (>72 hours post index procedure)	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.
Other	Percentage of Participants With Bleeding	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	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.
Other	Percentage of Participants With Acute Kidney Injury	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.	=7 days post index procedure
Other	Percentage of Participants With Major Vascular Complication	Major vascular complication - including access site related and non access site related	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.
Other	Percentage of Participants With Repeat Procedure for Valve-related Dysfunction	Repeat procedure for valve-related dysfunction (surgical or interventional therapy)	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.
Other	Percentage of Participants With Hospitalization for Valve-related Symptoms or Worsening Congestive Heart Failure	Hospitalization for valve-related symptoms or worsening congestive heart failure (New York Hear Association [NYHA] class III or IV)	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.
Other	Percentage of Participants With New Permanent Pacemaker Implantation	New permanent pacemaker implantation resulting from new or worsened conduction disturbances	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.
Other	Percentage of Participants With New Onset of Atrial Fibrillation or Atrial Flutter	New onset of atrial fibrillation or atrial flutter	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.
Other	Percentage of Participants With Coronary Obstruction	Coronary obstruction	=72 hours post index procedure
Other	Percentage of Participants With Ventricular Septal Perforation	Ventricular septal perforation	=72 hours post index procedure
Other	Percentage of Participants With Mitral Apparatus Damage	Mitral apparatus damage	=72 hours post index procedure
Other	Percentage of Participants With Cardiac Tamponade	Cardiac tamponade	=72 hours post index procedure
Other	Percentage of Participants With Prosthetic Aortic Valve Malpositioning	Prosthetic aortic valve malpositioning, including valve migration, valve embolization, or ectopic valve deployment	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.
Other	Percentage of Participants With Prosthetic Aortic Valve Thrombosis	Prosthetic aortic valve thrombosis	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.
Other	Percentage of Participants With Prosthetic Aortic Valve Endocarditis	Prosthetic aortic valve endocarditis	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.
Primary	Percentage of Participants With Events Included in the 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	30 days following procedure
Primary	Percentage of Participants With Events Included in the Primary Effectiveness Endpoint	Composite of all-cause mortality, disabling stroke, or moderate or greater paravalvular aortic regurgitation (based on core lab assessment).	1 year following procedure
Secondary	Percentage of Participants With Moderate or Greater Paravalvular Aortic Regurgitation	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).	1 year following procedure