Clinical trial NCT03735667: ACURATE IDE: Safety and Effectiveness Study of ACURATE Valve for Transcatheter Aortic Valve Replacement
Official title: ACURATE IDE: Transcatheter Replacement of Stenotic Aortic Valve Through Implantation of ACURATE in Subjects InDicatEd for TAVR
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Aortic Stenosis
Lead sponsor: Boston Scientific Corporation
Sponsor class: INDUSTRY
First posted: 2018-11-08
Enrollment: 1948
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate safety and effectiveness of the ACURATE Transfemoral Aortic Valve System for transcatheter aortic valve replacement (TAVR) in subjects with severe native aortic stenosis who are indicated for TAVR.

Detailed description: Subjects will be enrolled at up to 85 centers in the United States, Canada, Europe, and Australia. There will be up to 2,820 subjects in ACURATE IDE.

The ACURATE IDE study cohorts include the following.

* Main Randomized Cohort: A prospective, multicenter, 1:1 randomized controlled trial (RCT; ACURATE versus a commercially available balloon-expandable SAPIEN 3™ Transcatheter Heart Valve or future iteration \[SAPIEN 3; Edwards Lifesciences LLC, Irvine, CA, USA\] or a commercially available self-expanding CoreValve® Transcatheter Aortic Valve Replacement System, CoreValve® Evolut™ R Recapturable TAVR System, EVOLUT™ PRO System, or future iteration \[CoreValve; Medtronic, Inc., Dublin, Ireland\]). There will be up to 1,500 subjects in the RCT.
* Roll-In Cohort: A non-randomized roll-in phase with the test device. Centers that do not have implantation experience with the ACURATE neo™ Aortic Bioprosthesis (transfemoral delivery; Boston Scientific Corporation, Marlborough, MA, USA) will perform at least 2 roll-in cases before commencing treatment in the randomized cohort. Centers with prior experience with ACURATE are not required to do roll-in cases. Data from roll-in subjects will be summarized separately from the randomized cohort and will not be included in the primary endpoint analysis.
* 4D CT Imaging Substudy: Selected centers with the ability to perform high quality 4D computer tomography (CT) scans will include subjects in a 4D CT Imaging Substudy to assess the prevalence of reduced leaflet mobility and hypoattenuated leaflet thickening (HALT) and the relationship, if any, to clinical events. Subjects will be randomized to test (ACURATE) and control device.
* ACURATE Prime™ XL Nested Registry: A non-randomized, nested registry cohort of subjects who will receive the ACURATE Prime™ Transfemoral Aortic Valve System XL (ACURATE Prime XL Nested Registry). Participating centers will be a subset of United States centers that have enrolled subjects in ACURATE IDE. Data from subjects in this nested registry will be summarized separately from the randomized and roll-in cohorts.
* ACURATE Extended Durability Study: An additional 1:1 randomized study (ACURATE versus a commercially available balloon-expandable SAPIEN 3™ Transcatheter Heart Valve or future iteration \[SAPIEN 3; Edwards Lifesciences LLC, Irvine, CA, USA\] or a commercially available self-expanding CoreValve® Transcatheter Aortic Valve Replacement System, CoreValve® Evolut™ R Recapturable TAVR System, EVOLUT™ PRO System, or future iteration \[CoreValve; Medtronic, Inc., Dublin, Ireland\]) including only subjects considered to be at low surgical risk. Subjects will receive ACURATE neo2 (S, M, or L valve sizes) or ACURATE Prime XL. Data from subjects in the Extended Durability Study will be summarized separately from other cohorts.
* ACURATE Continued Access Study (CAS): An additional cohort of subjects receiving ACURATE neo2 (S, M, and L valve sizes) or ACURATE Prime XL. Data from subjects in the ACURATE CAS will be summarized separately from other cohorts and will be used to further assess performance and safety.

All subjects implanted will be followed at baseline, peri- and post-procedure, at discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, and then annually for up to 10 years post-procedure. Enrolled subjects who do not have a study device implanted will be assessed through 1-year post-procedure for safety/adverse events.

Eligibility criteria: Inclusion Criteria:

* IC1. Subject has documented severe symptomatic native aortic stenosis defined as follows: aortic valve area (AVA) ≤1.0 cm2 (or AVA index ≤0.6 cm2/m2) AND a mean pressure gradient ≥40 mmHg, OR maximal aortic valve velocity ≥4.0 m/s, OR Doppler velocity index ≤0.25 as measured by echocardiography and/or invasive hemodynamics.

Note: In cases of low flow, low gradient aortic stenosis with left ventricular dysfunction (ejection fraction \<50%), dobutamine can be used to assess the grade of aortic stenosis (maximum dobutamine dose of 20 mcg/kg/min recommended); the subject may be enrolled if echocardiographic criteria are met with this augmentation.

* IC2. Subject has a documented aortic annulus size of ≥20.5 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 Main Randomized Cohort and the Extended Durability Study, is deemed treatable with an available size of both test and control device.
* IC3. For subjects with symptomatic aortic valve stenosis per IC1 definition above, functional status is NYHA Functional Class ≥ II.
* IC4. Heart team (which must include an experienced cardiac interventionalist and an experienced cardiac surgeon) agrees that the subject is indicated for TAVR, is likely to benefit from valve replacement, and TAVR is appropriate.
* IC5. Subject (or legal representative) understands the study requirements and the treatment procedures, and provides written informed consent.
* IC6. 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.
* IC7. Subject is expected to be able to take the protocol-required adjunctive pharmacologic therapy.

Exclusion Criteria:

* EC1. Subject has a 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 clinically confirmed by a neurologist or neuroimaging within the past 6 months prior to study enrollment.
* EC4. Subject is on renal replacement therapy or has eGFR \<20.
* EC5. Subject has a pre-existing prosthetic aortic or mitral valve.
* EC6. Subject has severe (4+) aortic, tricuspid, or mitral regurgitation.
* EC7. Subject has moderate or severe mitral stenosis (mitral valve area ≤1.5 cm2 and diastolic pressure half-time ≥150 ms, Stage C or D76).
* EC8. Subject has a need for emergency surgery for any reason.
* EC9. Subject has a history of endocarditis within 6 months of index procedure or evidence of an active systemic infection or sepsis.
* EC10. Subject has echocardiographic evidence of new intra-cardiac vegetation or intraventricular or paravalvular thrombus requiring intervention.
* EC11. Subject has platelet count \<50,000 cells/mm3 or \>700,000 cells/mm3, or white blood cell count \<1,000 cells/mm3.
* EC12. 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.
* EC13. Subject has known hypersensitivity to contrast agents that cannot be adequately pre-medicated, or has known hypersensitivity to the protocol required medications (aspirin, all P2Y12 inhibitors, heparin), or to the individual components of the test or control valve (nickel, titanium, stainless steel, platinum, iridium or polyethylene terephthalate \[PET\]).
* 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 cardiomyopathy.
* EC16. Subject has any therapeutic invasive cardiac or vascular procedure within 30 days prior to the index procedure (except for balloon aortic valvuloplasty, pacemaker implantation, or implantable cardioverter defibrillator 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 arterial access that is not acceptable for the study device (test or control) delivery systems as defined in the device (test or control) Directions For Use.
* EC21. Subject has either of the following:

  * 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 thick, protruding, ulcerated atheroma in the aortic arch), OR
  * Severe/eccentric calcification of the aortic annulus that would prevent safe implantation of the TAVR prosthesis.
* EC22. Subject has current problems with substance abuse (e.g., alcohol, etc.) that may interfere with the subject's participation in this study.
* EC23. Subject is participating in another investigational drug or device study that has not reached its primary endpoint or subject intends to participate in another investigational device clinical trial within 12 months after index procedure.
* EC24. 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.
* EC25. Subject has severe incapacitating dementia.

Additional exclusion criteria apply to subjects considered for enrollment in the CT Imaging Substudy as listed below.

* AEC1. Subject has eGFR \<30 mL/min (chronic kidney disease stage IV or stage V)
* AEC2. Subject has atrial fibrillation that cannot be rate controlled to ventricular response rate \< 60 bpm.
* AEC3. Subject is expected to undergo chronic anticoagulation therapy after the index procedure.

Note: Subjects treated with short-term anticoagulation post procedure can be included in the CT Imaging Substudy; in these subjects the 30-day imaging will be performed 30 days after discontinuation of anticoagulation.

Primary outcomes:
measure: Composite Rate of All-cause Mortality, All Stroke, and Rehospitalization* at 1 Year in the Main Randomized Cohort.
timeFrame: Participants will be followed for the duration of hospital stay through 1 year.
Secondary outcomes:
Other outcomes:
measure: Rate of Mortality: All-cause, Cardiovascular, and Non-cardiovascular
timeFrame: Participants will be followed peri- and post-procedure, at discharge or 7 days post-procedure (whichever comes first), 30 Days, 6 Months, and 1 Year. Data for 2-10 years will be posted once data is complete.
measure: Rate of All Stroke: Disabling and Non-disabling
timeFrame: Participants will be followed peri- and post-procedure, at discharge or 7 days post-procedure (whichever comes first), 30 Days, 6 Months, and 1 Year. Data for 2-10 years will be posted once data is complete.
measure: Rate of Myocardial Infarction (MI): Periprocedural (≤72 Hours Post Index Procedure) and Spontaneous (>72 Hours Post Index Procedure)
timeFrame: Participants will be followed peri- and post-procedure, at discharge or 7 days post-procedure (whichever comes first), 30 Days, 6 Months, and 1 Year. Data for 2-10 years will be posted once data is complete.
measure: Rate of Bleeding: Life-threatening (or Disabling) and Major
timeFrame: Participants will be followed peri- and post-procedure, at discharge or 7 days post-procedure (whichever comes first), 30 Days, 6 Months, and 1 Year. Data for 2-5 years will be posted once data is complete.
measure: Rate of Major Vascular Complications
timeFrame: Participants will be followed peri- and post-procedure, at discharge or 7 days post-procedure (whichever comes first), 30 Days, 6 Months, and 1 Year. Data for 2-5 years will be posted once data is complete.
measure: Rate of Repeat Procedure for Valve-related Dysfunction (Surgical or Interventional Therapy)
timeFrame: Participants will be followed peri- and post-procedure, at discharge or 7 days post-procedure (whichever comes first), 30 Days, 6 Months, and 1 Year. Data for 2-10 years will be posted once data is complete.
measure: Rate of Hospitalization for Valve-related Symptoms or Worsening Congestive Heart Failure (NYHA Class III or IV)
timeFrame: Participants will be followed peri- and post-procedure, at discharge or 7 days post-procedure (whichever comes first), 30 Days, 6 Months, and 1 Year. Data for 2-10 years will be posted once data is complete.
measure: Rate of New Permanent Pacemaker Implantation (PPI) Resulting From New or Worsened Conduction Disturbances
timeFrame: Participants will be followed peri- and post-procedure, at discharge or 7 days post-procedure (whichever comes first), 30 Days, 6 Months, and 1 Year. Data for 2-10 years will be posted once data is complete.
measure: Rate of New Onset of Atrial Fibrillation or Atrial Flutter
timeFrame: Participants will be followed peri- and post-procedure, at discharge or 7 days post-procedure (whichever comes first), 30 Days, 6 Months, and 1 Year. Data for 2-10 years will be posted once data is complete.
measure: Rate of Acute Kidney Injury (AKI; ≤7 Days Post Index Procedure): Based on the AKIN System Stage 3 (Including Renal Replacement Therapy) or Stage 2
timeFrame: Participants will be followed peri- and post-procedure, through 7 days post index procedure.
measure: Rate of Coronary Obstruction: Periprocedural
timeFrame: Participants will be followed through 72 hours post index procedure
measure: Rate of Ventricular Septal Perforation: Periprocedural
timeFrame: Participants will be followed through 72 hours post index procedure
measure: Rate of Mitral Apparatus Damage: Periprocedural
timeFrame: Participants will be followed through 72 hours post index procedure
measure: Rate of Cardiac Tamponade: Periprocedural
timeFrame: Participants will be followed through 72 hours post index procedure
measure: Rate of Valve Migration
timeFrame: Participants will be followed peri- and post-procedure, at discharge or 7 days post-procedure (whichever comes first), 30 Days, 6 Months, and 1 Year. Data for 2-10 years will be posted once data is complete.
measure: Rate of Valve Embolization
timeFrame: Participants will be followed peri- and post-procedure, at discharge or 7 days post-procedure (whichever comes first), 30 Days, 6 Months, and 1 Year. Data for 2-10 years will be posted once data is complete.
measure: Rate of Ectopic Valve Deployment
timeFrame: Participants will be followed peri- and post-procedure through discharge or 7 days post-procedure (whichever comes first).
measure: Rate of Transcatheter Aortic Valve (TAV)-In-TAV Deployment
timeFrame: Participants will be followed peri- and post-procedure, at discharge or 7 days post-procedure (whichever comes first), 30 Days, 6 Months, and 1 Year. Data for 2-10 years will be posted once data is complete.
measure: Rate of Prosthetic Aortic Valve Thrombosis
timeFrame: Participants will be followed peri- and post-procedure, at discharge or 7 days post-procedure (whichever comes first), 30 Days, 6 Months, and 1 Year. Data for 2-10 years will be posted once data is complete.
measure: Rate of Prosthetic Aortic Valve Endocarditis
timeFrame: Participants will be followed peri- and post-procedure, at discharge or 7 days post-procedure (whichever comes first), 30 Days, 6 Months, and 1 Year. Data for 2-10 years will be posted once data is complete.
measure: Rate of Successful Vascular Access, Delivery and Deployment of the Study Valve, and Successful Retrieval of the Delivery System (Site Reported Assessment)
timeFrame: Participants will be followed for the duration of their procedure, an expected average of 1 Day (peri- and post-procedure)
measure: Grade of Aortic Valve Regurgitation: Paravalvular, Central and Combined (Echocardiographic Assessment)
timeFrame: Participants will be assessed pre-procedure, at discharge or 7 days post-procedure (whichever comes first), 30 Days, 6 Months, and 1 Year. Data for 2-5 years, 7 years, and 10 years will be posted once data is complete.
measure: Rate of Device Success
timeFrame: Participants will be followed for the duration of their procedure, an expected average of 1 Day (post-procedure)
measure: Effective Orifice Area (EOA)
timeFrame: Participants will be assessed pre-procedure, at discharge or 7 days post-procedure (whichever comes first), 30 Days, 6 Months, and 1 Year. Data for 2-5 years, 7 years, and 10 years will be posted once data is complete.
measure: Mean Aortic Gradient
timeFrame: Participants will be assessed pre-procedure, at discharge or 7 days post-procedure (whichever comes first), 30 Days, 6 Months, and 1 Year. Data for 2-5 years, 7 years, and 10 years will be posted once data is complete.
measure: New York Heart Association (NYHA) Functional Status Classification
timeFrame: Participants will be followed peri- and post-procedure, at discharge or 7 days post-procedure (whichever comes first), 30 Days, 6 Months, and 1 Year. Data for 2-5 years, 7 years, and 10 years will be posted once data is complete.
measure: Health Status: Kansas City Cardiomyopathy Questionnaire (KCCQ) Quality of Life Assessment - Change From Baseline
timeFrame: Participants will be assessed at baseline, 30 Days, and 1 Year. Data for 5 years will be posted once data is complete.
measure: Health Status: SF-12 Quality of Life Questionnaire Assessment - Change From Baseline
timeFrame: Participants will be assessed at baseline, 30 Days, and 1 Year. Data for 5 years will be posted once data is complete.
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Banner Good Samaritan
state: Arizona
city: Scottsdale
country: United States
facility: HonorHealth Scottsdale Healthcare
state: Arizona
city: Tucson
country: United States
facility: TMC HealthCare
state: Arizona
city: Little Rock
country: United States
facility: Baptist Health Medical Center
state: Arkansas
city: La Jolla
country: United States
facility: Scripps Clinic
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente Los Angeles
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Heart Institute
state: California
city: Sacramento
country: United States
facility: University of California, Davis Medical Center
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente - San Francisco
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Clearwater
country: United States
facility: Morton Plant Hospital
state: Florida
city: Orlando
country: United States
facility: Orlando Regional Medical Center
state: Florida
city: Atlanta
country: United States
facility: Piedmont Hospital
state: Georgia
city: Evanston
country: United States
facility: NorthShore University Health Study Coordinator
state: Illinois
city: Oak Lawn
country: United States
facility: Advocate Christ Medical Center
state: Illinois
city: Springfield
country: United States
facility: St. John's Hospital (Prairie)
state: Illinois
city: Indianapolis
country: United States
facility: St. Vincent's Hospital
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Baltimore
country: United States
facility: Union Memorial Hospital
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Abbott Northwestern Hospital
state: Minnesota
city: Saint Cloud
country: United States
facility: CentraCare Heart and Vascular Center
state: Minnesota
city: Saint Paul
country: United States
facility: St. Joseph's Hospital-St. Paul
state: Minnesota
city: Browns Mills
country: United States
facility: Deborah Heart and Lung Center
state: New Jersey
city: Englewood
country: United States
facility: Englewood Health
state: New Jersey
city: New Brunswick
country: United States
facility: Robert Wood Johnson Medical Center
state: New Jersey
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: Bronx
country: United States
facility: Montefiore-Jack D. Weiler Hospital
state: New York
city: Buffalo
country: United States
facility: Kaleida Health
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center/NYPH
state: New York
city: New York
country: United States
facility: Cornell Presbyterian - New York
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas Medical Center
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 Christ Hospital
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals of Cleveland
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: OhioHealth Research and Innovation Institute
state: Ohio
city: Oklahoma City
country: United States
facility: Integris Baptist Medical Center
state: Oklahoma
city: Portland
country: United States
facility: Providence Heart Institute
state: Oregon
city: Springfield
country: United States
facility: Sacred Heart Medical Center - Riverbend
state: Oregon
city: Harrisburg
country: United States
facility: UPMC - Pinnacle
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Pittsburgh
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau
state: Pennsylvania
city: York
country: United States
facility: WellSpan York Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: West Columbia
country: United States
facility: Lexington Medical Center
state: South Carolina
city: Nashville
country: United States
facility: St Thomas Ascension
state: Tennessee
city: Austin
country: United States
facility: Austin Heart
state: Texas
city: Dallas
country: United States
facility: Baylor Heart and Vascular Hospital
state: Texas
city: Dallas
country: United States
facility: Presbyterian Hospital of Dallas
state: Texas
city: Houston
country: United States
facility: The Methodist Hospital Research Institute
state: Texas
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
city: Plano
country: United States
facility: Baylor Regional Medical Center at Plano
state: Texas
city: San Antonio
country: United States
facility: Methodist Healthcare System of San Antonio dba Methodist Hospital
state: Texas
city: Burlington
country: United States
facility: The University of Vermont Medical Center
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Norfolk
country: United States
facility: Sentara Norfolk General Hospital
state: Virginia
city: Everett
country: United States
facility: Providence Regional Medical Center
state: Washington
city: Green Bay
country: United States
facility: Bellin Health
state: Wisconsin
city: Milwaukee
country: United States
facility: Aurora Research Institute
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin - Froedtert Hospital
state: Wisconsin
city: New Westminster
country: Canada
facility: Royal Columbian Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: Providence Health - St. Paul's Hospital
state: British Columbia
city: London
country: Canada
facility: London Health Sciences
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Montreal
country: Canada
facility: Centre Hospitalier de l'Universite de Montreal (CHUM)
state: Quebec
city: Québec
country: Canada
facility: Institut Universitaire de Cardiologie et de Pneumologie de Quebec (IUCPQ)
Study officials:
affiliation: Cedars-Sinai Heart Institute
name: Raj R. Makkar, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Methodist DeBakey Heart & Vascular Center
name: Michael J. Reardon, MD
role: PRINCIPAL_INVESTIGATOR
References: