Clinical trial NCT02207569: Medtronic CoreValve Evolut R U.S. Clinical Study
Official title: Medtronic CoreValve Evolut R United States IDE Clinical Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Aortic Stenosis
Lead sponsor: Medtronic Cardiovascular
Sponsor class: INDUSTRY
First posted: 2014-08-04
Enrollment: 241
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The study objectives are to assess the safety and efficacy of the CoreValve Evolut R transcatheter aortic valve replacement (TAVR) system in patients with severe symptomatic aortic stenosis are considered at high or extreme risk for surgical aortic valve replacement.

Detailed description: This objective will be accomplished by a prospective, single arm, historical controlled, multi-site study involving a minimum of 150 implanted subjects with no more than 250 implanted subjects at up to 25 study sites in the United States. Procedural and 30 day safety and efficacy results from this study will be compared to appropriate historical control data for the Medtronic CoreValve System. Subjects will be followed up to 5 years following implantation.

The enrollment phase of the study is estimated to take approximately 6-9 months. As each implanted subject is to be followed up to 5 years, the estimated study duration is approximately 66-69 months, excluding the time required for preparing the final report.

Eligibility criteria: Inclusion Criteria - Severe aortic stenosis, defined as aortic valve area of \< 1.0 cm2 (or aortic valve area index of \< 0.6 cm2/m2) by the continuity equation, AND mean gradient \> 40 mmHg or maximal aortic valve velocity \> 4.0 m/sec by resting echocardiogram.

Subjects with low-flow/low gradient severe aortic stenosis can be included, provided low-dose dobutamine or exercise stress echocardiography demonstrates a mean gradient of \>40 mmHg or a maximal aortic valve velocity of \>4.0 m/sec, AND aortic valve area of \<1.0cm2 (or aortic valve area index of \<0.6 cm2/m2).

* STS score of ≥ 8 OR documented heart team agreement of ≥ high risk for AVR due to frailty or co-morbidities.
* Symptoms of aortic stenosis, AND NYHA Functional Class II or greater
* The subject and the treating physician agree that the subject will return for all required post-procedure follow-up visits.

Exclusion Criteria

* Any condition considered a contraindication for placement of a bioprosthetic valve (e.g. subject is indicated for mechanical prosthetic valve).
* A known hypersensitivity or contraindication to any of the following which cannot be adequately pre-medicated: aspirin or heparin (HIT/HITTS) and bivalirudin, ticlopidine and clopidogrel, Nitinol (titanium or nickel), contrast media
* Blood dyscrasias as defined: leukopenia (WBC \< 1000 mm3), thrombocytopenia (platelet count \<50,000 cells/mm3), history of bleeding diathesis or coagulopathy, or hypercoagulable states.
* Untreated clinically significant coronary artery disease requiring revascularization.
* Severe left ventricular dysfunction with left ventricular ejection fraction (LVEF) \< 20% by echocardiography, contrast ventriculography, or radionuclide ventriculography.
* End stage renal disease requiring chronic dialysis or creatinine clearance \< 20 cc/min.
* Ongoing sepsis, including active endocarditis.
* Any percutaneous coronary or peripheral interventional procedure with a bare metal or drug eluting stent performed within 30 days prior to the study procedure.
* Symptomatic carotid or vertebral artery disease or successful treatment of carotid stenosis within 10 weeks of Heart Team assessment.
* Cardiogenic shock manifested by low cardiac output, vasopressor dependence, or mechanical hemodynamic support.
* Recent (within 6 months of Heart Team assessment) cerebrovascular accident (CVA) or transient ischemic attack (TIA).
* Gastrointestinal (GI) bleeding that would preclude anticoagulation.
* Subject refuses a blood transfusion.
* Severe dementia (resulting in either inability to provide informed consent for the study/procedure, prevents independent lifestyle outside of a chronic care facility, or will fundamentally complicate rehabilitation from the procedure or compliance with follow-up visits).
* Estimated life expectancy of less than 12 months due to associated non-cardiac co-morbid conditions.
* Other medical, social, or psychological conditions that in the opinion of the investigator precludes the subject from appropriate consent or adherence to the protocol required follow-ups exams.
* Currently participating in an investigational drug or another device study (excluding registries).
* Evidence of an acute myocardial infarction ≤ 30 days before the study procedure.
* Need for emergency surgery for any reason.
* Liver failure (Child-Pugh class C).
* Subject is pregnant or breast feeding.

Anatomical exclusion criteria:

* Pre-existing prosthetic heart valve in any position.
* Mixed aortic valve disease (aortic stenosis with severe aortic regurgitation).
* Severe mitral regurgitation.
* Severe tricuspid regurgitation.
* Moderate or severe mitral stenosis.
* Hypertrophic obstructive cardiomyopathy.
* Echocardiographic or Multi-Slice Computed Tomography (MSCT) evidence of intracardiac mass, thrombus, or vegetation.
* Congenital bicuspid or unicuspid valve verified by echocardiography.

For transfemoral or transaxillary (subclavian) acess:

- Access vessel diameter \<5.0mm or \<6.0mm for patent LIMA

Primary outcomes:
measure: All-cause Mortality at 30 Days by Percent
timeFrame: Assessed at 30 days post-implantation
measure: Percentage of Patients With Disabling Stroke at 30 Days
timeFrame: Assessed at 30 days post-implantation
measure: Percent Device Success Rate Between 24 and 7 Day
timeFrame: Assessed at 24 hours to seven days post implantation
measure: Percentage of Patients With Less Than Moderate Prosthetic Regurgitation at Early Post Procedure Echocardiogram (24 Hours to 7 Days)
timeFrame: Assessed at 24 hours to 7 days post implantation
Secondary outcomes:
measure: Individual Component of VARC II Safety Endpoint: Percentage of People Requiring Valve-related Dysfunction Requiring Repeat Procedure (BAV, TAVI, or SAVR)
timeFrame: Assessed at 30 days post-implantation
measure: Coronary Artery Obstruction Requiring Intervention.
timeFrame: Assessed at 30 days post-implantation
measure: Percent VARC II Combined Safety Endpoint at 30 Days
timeFrame: Assessed at 30 days post-implantation
measure: Percent of Patients With Acute Kidney Injury: Stage 2 or 3 (Including Renal Replacement Therapy).
timeFrame: Assessed at 30 days post-implantation
measure: Percentage of Patients With Life-threatening or Disabling Bleeding Event Rate
timeFrame: Assessed at 30 days post-implantation
measure: Percent Rate of Patients Who Received New Permanent Pacemaker Implant at 30 Days
timeFrame: Assessed at 30 days
measure: Percent Resheath and Recapture Success Rate
timeFrame: Assessed intra-procedurally
measure: Hemodynamic Performance -Mean Gradient
timeFrame: Assessed at baseline, 30 days, 6 months, and 1 year
measure: Major Vascular Complication
timeFrame: Assessed at 30 days post-implantation
measure: Hemodynamic Performance - Aortic Valve Area
timeFrame: Assessed at baseline, 30 days, 6 months, and 1 year
measure: Hemodynamic Performance: Total Prosthetic Valve Regurgitation Graded as Moderate or Severe
timeFrame: Assessed at 30 days, 6 months, and 1 year
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Banner Good Samaritan Medical Center
state: Arizona
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Washington
country: United States
facility: Washington Hospital Center/Medstar
state: District of Columbia
city: Indianapolis
country: United States
facility: St. Vincent Heart Center of Indiana/The Care Group, LLC
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas
state: Kansas
city: Baltimore
country: United States
facility: The Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconcess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health Systems
state: Michigan
city: Detroit
country: United States
facility: Detroit Medical Center Cardiovascular Institute
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health
state: Michigan
city: Morristown
country: United States
facility: Morristown Memorial Hospital
state: New Jersey
city: New York
country: United States
facility: New York Langone Medical Center
state: New York
city: New York
country: United States
facility: The Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Roslyn
country: United States
facility: St. Francis Hospital
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbus
country: United States
facility: Riverside Methodist Hospital/Ohio Health Research Institute
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburg Medical Center
state: Pennsylvania
city: Wormleysburg
country: United States
facility: Pinnacle Health
state: Pennsylvania
city: Dallas
country: United States
facility: Baylor Heart and Vascular Hospital
state: Texas
city: Houston
country: United States
facility: The Methodist DeBakey Heart & Vasc Ctr/The Methodist Hosp
state: Texas
city: Milwaukee
country: United States
facility: Aurora Health Care/St Luke's Medical Center
state: Wisconsin
Study officials:
affiliation: New York Langone Medical Center
name: Mathew R Williams, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Popma JJ, Reardon MJ, Khabbaz K, Harrison JK, Hughes GC, Kodali S, George I, Deeb GM, Chetcuti S, Kipperman R, Brown J, Qiao H, Slater J, Williams MR. Early Clinical Outcomes After Transcatheter Aortic Valve Replacement Using a Novel Self-Expanding Bioprosthesis in Patients With Severe Aortic Stenosis Who Are Suboptimal for Surgery: Results of the Evolut R U.S. Study. JACC Cardiovasc Interv. 2017 Feb 13;10(3):268-275. doi: 10.1016/j.jcin.2016.08.050.