Clinical trial NCT02202434: Safety and Efficacy Study of Lotus Valve for Transcatheter Aortic Valve Replacement
Official title: REPRISE III: Repositionable Percutaneous Replacement of Stenotic Aortic Valve Through Implantation of Lotus™ Valve System - Randomized Clinical Evaluation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Aortic Stenosis
Lead sponsor: Boston Scientific Corporation
Sponsor class: INDUSTRY
First posted: 2014-07-29
Enrollment: 1425
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Percentage of Participants With Events Included in the Primary Safety Endpoint
timeFrame: 30 days following procedure
measure: Percentage of Participants With Events Included in the Primary Effectiveness Endpoint
timeFrame: 1 year following procedure
Secondary outcomes:
measure: Percentage of Participants With Moderate or Greater Paravalvular Aortic Regurgitation
timeFrame: 1 year following procedure
Other outcomes:
measure: Percentage of Participants With Successful Deployment of the Study Valve
timeFrame: at discharge or 7 days post-procedure (whichever comes first)
measure: Percentage of Participants With Successful Retrieval of the Study Valve if Retrieval is Attempted
timeFrame: at discharge or 7 days post-procedure (whichever comes first)
measure: Percentage of Participants With Successful Repositioning of the Study Valve if Repositioning is Attempted
timeFrame: at discharge or 7 days post-procedure (whichever comes first)
measure: Percentage of Participants With Each Grade of Aortic Valve Regurgitation in Each Location: Paravalvular, Central, and Combined
timeFrame: at discharge or 7 days post-procedure (whichever comes first)
measure: Percentage of Participants With Clinical Procedural Success
timeFrame: 30 days post procedure
measure: Percentage of Participants With Procedural Success
timeFrame: 30 days post procedure
measure: Additional Indications of Prosthetic Aortic Valve Performance as Measured by Transthoracic Echocardiography 1
timeFrame: 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.
measure: Additional Indications of Prosthetic Aortic Valve Performance as Measured by Transthoracic Echocardiography 2
timeFrame: 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.
measure: Additional Indications of Prosthetic Aortic Valve Performance as Measured by Transthoracic Echocardiography 3
timeFrame: 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.
measure: Percentage of Participants With Additional Indications of Prosthetic Aortic Valve Performance as Measured by Transthoracic Echocardiography 4
timeFrame: 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.
measure: Health Status as Evaluated by Quality of Life Questionnaires
timeFrame: Assessed at Baseline, 1 and 6 months; and 1, 3, and 5 years, at Baseline, 1 and 6 months and 1 Year reported
measure: Percentage of Participants With Mortality
timeFrame: 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.
measure: Percentage of Participants With Stroke
timeFrame: 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.
measure: Percentage of Participants With Myocardial Infarction (MI)
timeFrame: 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.
measure: Percentage of Participants With Bleeding
timeFrame: 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.
measure: Percentage of Participants With Acute Kidney Injury
timeFrame: ≤7 days post index procedure
measure: Percentage of Participants With Major Vascular Complication
timeFrame: 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.
measure: Percentage of Participants With Repeat Procedure for Valve-related Dysfunction
timeFrame: 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.
measure: Percentage of Participants With Hospitalization for Valve-related Symptoms or Worsening Congestive Heart Failure
timeFrame: 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.
measure: Percentage of Participants With New Permanent Pacemaker Implantation
timeFrame: 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.
measure: Percentage of Participants With New Onset of Atrial Fibrillation or Atrial Flutter
timeFrame: 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.
measure: Percentage of Participants With Coronary Obstruction
timeFrame: ≤72 hours post index procedure
measure: Percentage of Participants With Ventricular Septal Perforation
timeFrame: ≤72 hours post index procedure
measure: Percentage of Participants With Mitral Apparatus Damage
timeFrame: ≤72 hours post index procedure
measure: Percentage of Participants With Cardiac Tamponade
timeFrame: ≤72 hours post index procedure
measure: Percentage of Participants With Prosthetic Aortic Valve Malpositioning
timeFrame: 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.
measure: Percentage of Participants With Prosthetic Aortic Valve Thrombosis
timeFrame: 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.
measure: Percentage of Participants With Prosthetic Aortic Valve Endocarditis
timeFrame: 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.
Locations:
city: Phoenix
country: United States
facility: Banner Good Samaritan
state: Arizona
city: Scottsdale
country: United States
facility: Scottsdale Healthcare - Shea
state: Arizona
city: La Jolla
country: United States
facility: Scripps Clinic
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Palo Alto
country: United States
facility: Veteran's Administration Palo Alto Medical Center
state: California
city: Sacramento
country: United States
facility: University of California at Davis Medical Center
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Clearwater
country: United States
facility: Morton Plant Mease Healthcare System
state: Florida
city: Delray Beach
country: United States
facility: Delray Medical Center
state: Florida
city: Miami
country: United States
facility: University of Miami Hospital
state: Florida
city: Miami
country: United States
facility: Baptist Cardiac and Vascular Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Atlanta
country: United States
facility: Piedmont Hospital
state: Georgia
city: Evanston
country: United States
facility: Evanston Hospital
state: Illinois
city: Springfield
country: United States
facility: St. John's Hospital - Prairie Cardiovascular Consultants
state: Illinois
city: Indianapolis
country: United States
facility: St. Vincent's Hospital
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Hospital
state: Kansas
city: Baltimore
country: United States
facility: Union Memorial Hospital
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Petoskey
country: United States
facility: Cardiac & Vascular Rearch Center of Northern Michigan - Northern Michigan Hospital
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Abbott Northwestern Hospital - Minneapolis Heart Institute
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine - Barnes Jewish Medical Center
state: Missouri
city: Morristown
country: United States
facility: Morristown Memorial Hospital
state: New Jersey
city: Buffalo
country: United States
facility: Kaleida Health
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Raleigh
country: United States
facility: NC Heart and Vascular Research - Rex Hospital
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University School of Medicine
state: North Carolina
city: Cincinnati
country: United States
facility: Lindner Center for Research and Education at The Christ Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Columbus
country: United States
facility: Ohio Health Research and Innovation Institute - Riverside Methodist Hospital
state: Ohio
city: Portland
country: United States
facility: Providence St. Vincent Medical Center
state: Oregon
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Dallas
country: United States
facility: Baylor Heart and Vascular Hospital
state: Texas
city: Dallas
country: United States
facility: Medical City Dallas Hospital
state: Texas
city: Houston
country: United States
facility: Methodist DeBakey Heart & Vascular Center
state: Texas
city: San Antonio
country: United States
facility: Methodist Heart Hospital
state: Texas
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Aurora St. Luke's Medical Center
state: Wisconsin
city: Chermside
country: Australia
facility: The Prince Charles Hospital
state: Queensland
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Vancouver
country: Canada
facility: Providence Health - St. Paul's Hospital
state: British Columbia
city: Montreal
country: Canada
facility: McGill University Health Centre, Royal Victoria Hospital
state: Quebec
city: Toulouse
country: France
facility: Clinique Pasteur
state: Midi-Pyrenees
city: Toulouse
country: France
facility: Centre Hôpital Universitaire Rangueil
city: Leipzig
country: Germany
facility: Herzzentrum Universität Leipzig
state: Saxony
city: Hamburg
country: Germany
facility: Universitares Herzzentrum UKE (Hamburg)
city: Rotterdam
country: Netherlands
facility: Erasmus MC - University Medical Center Rotterdam
Study officials:
affiliation: Scottsdale Healthcare - Shea
name: David Rizik, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Methodist Hospital Research Institute
name: Michael J Reardon, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rizik DG, Rajagopal V, Makkar RR, Bajwa T, Kleiman NS, Linke A, Kereiakes DJ, Waksman R, Thourani VH, Stoler RC, Mishkel GJ, Iyer VS, Buchbinder M, Gotberg M, Bjursten H, Allocco DJ, Reardon MJ. Long-term Outcomes of Transcatheter Aortic Valve Replacement With the Lotus Valve vs CoreValve/EvolutR: A Secondary Analysis of the REPRISE III Randomized Clinical Trial. JAMA Netw Open. 2022 Oct 3;5(10):e2238792. doi: 10.1001/jamanetworkopen.2022.38792.
citation: Goel K, O'Leary JM, Barker CM, Levack M, Rajagopal V, Makkar RR, Bajwa T, Kleiman N, Linke A, Kereiakes DJ, Waksman R, Allocco DJ, Rizik DG, Reardon MJ, Lindman BR. Clinical Implications of Physical Function and Resilience in Patients Undergoing Transcatheter Aortic Valve Replacement. J Am Heart Assoc. 2020 Sep;9(17):e017075. doi: 10.1161/JAHA.120.017075. Epub 2020 Aug 28.
citation: Meduri CU, Kereiakes DJ, Rajagopal V, Makkar RR, O'Hair D, Linke A, Waksman R, Babliaros V, Stoler RC, Mishkel GJ, Rizik DG, Iyer VS, Schindler J, Allocco DJ, Meredith IT, Feldman TE, Reardon MJ. Pacemaker Implantation and Dependency After Transcatheter Aortic Valve Replacement in the REPRISE III Trial. J Am Heart Assoc. 2019 Nov 5;8(21):e012594. doi: 10.1161/JAHA.119.012594. Epub 2019 Oct 23.
citation: Reardon MJ, Feldman TE, Meduri CU, Makkar RR, O'Hair D, Linke A, Kereiakes DJ, Waksman R, Babliaros V, Stoler RC, Mishkel GJ, Rizik DG, Iyer VS, Gleason TG, Tchetche D, Rovin JD, Lhermusier T, Carrie D, Hodson RW, Allocco DJ, Meredith IT; Reprise III Investigators. Two-Year Outcomes After Transcatheter Aortic Valve Replacement With Mechanical vs Self-expanding Valves: The REPRISE III Randomized Clinical Trial. JAMA Cardiol. 2019 Mar 1;4(3):223-229. doi: 10.1001/jamacardio.2019.0091.
citation: Asch FM, Vannan MA, Singh S, Khandheria B, Little SH, Allocco DJ, Meredith IT, Feldman TE, Reardon MJ, Weissman NJ. Hemodynamic and Echocardiographic Comparison of the Lotus and CoreValve Transcatheter Aortic Valves in Patients With High and Extreme Surgical Risk: An Analysis From the REPRISE III Randomized Controlled Trial. Circulation. 2018 Jun 12;137(24):2557-2567. doi: 10.1161/CIRCULATIONAHA.118.034129. Epub 2018 Mar 12.
citation: Feldman TE, Reardon MJ, Rajagopal V, Makkar RR, Bajwa TK, Kleiman NS, Linke A, Kereiakes DJ, Waksman R, Thourani VH, Stoler RC, Mishkel GJ, Rizik DG, Iyer VS, Gleason TG, Tchetche D, Rovin JD, Buchbinder M, Meredith IT, Gotberg M, Bjursten H, Meduri C, Salinger MH, Allocco DJ, Dawkins KD. Effect of Mechanically Expanded vs Self-Expanding Transcatheter Aortic Valve Replacement on Mortality and Major Adverse Clinical Events in High-Risk Patients With Aortic Stenosis: The REPRISE III Randomized Clinical Trial. JAMA. 2018 Jan 2;319(1):27-37. doi: 10.1001/jama.2017.19132.