Clinical trial NCT05149755: Evolut™ EXPAND TAVR II Pivotal Trial
Official title: Evolut™ EXPAND TAVR II Pivotal Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Moderate Aortic Valve Stenosis
Keywords: aortic
stenosis
moderate
valve
TAVR
Lead sponsor: Medtronic Cardiovascular
Sponsor class: INDUSTRY
First posted: 2021-12-08
Enrollment: 650
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Obtain safety and effectiveness data to support indication expansion for the Medtronic TAVR System to include patients with moderate, AS.

Detailed description: Multi-center, international, prospective, randomized study. Subjects will be randomized to either transcatheter aortic valve replacement (TAVR) with the Evolut PRO+ TAVR System, or Evolut FX System, and guideline-directed management (GDMT) or GDMT alone.

Eligibility criteria: Key Inclusion Criteria:

o Moderate AS, defined as follows by transthoracic echo (TTE) as assessed by the ECL:

* AVA \>1.0 cm² and \<1.5cm²; or
* AVA ≤ 1.0 cm² with AVAI \> 0.6cm²/m² if BMI \< 30 kg/m²: or
* AVA ≤ 1.0 cm² with AVAI \> 0.5cm²/m² if BMI ≥ 30 kg/m²:

and

* Max aortic velocity ≥ 3.0 m/sec. and \< 4.0 m/sec. or
* Mean aortic gradient ≥ 20mmHg and \< 40.0 mmHg

Any of the following at-risk features:

* Symptoms of AS, defined as:
* NYHA ≥ Class II, or
* Reduced functional capacity, defined as

  * 6MWT \< 300 meters, or
  * \< 85% of age-sex predicted METs on exercise tolerance testing (ETT)
* Documented heart failure event or hospitalization for heart failure within 1 calendar year prior to consent
* NT-proBNP ≥ 600 pg/ml (or BNP ≥ 80 pg/ml), or
* Persistent AF or Paroxysmal AF episode within 6 months prior to consent, or
* Elevated aortic valve calcium score (\>1200 AU for females and \> 2000 AU for males) as assessed by the MDCT core lab, or
* Any of the following by the qualifying TTE as assessed by the ECL:

  * Global longitudinal strain ≤16% (absolute value), or
  * E/e' ≥ 14.0 (average of medial and lateral velocities), or
  * Diastolic dysfunction ≥ Grade II, or
  * LVEF \< 60%
  * Stroke Volume Index \< 35 ml/m²
* Anatomically suitable for transfemoral TAVR using the Medtronic Evolut PRO+ or Evolut FX system
* The subject and the treating physician agree the subject will return for all required follow-up visits

Key Exclusion Criteria:

* Age \< 65 years
* LVEF ≤ 20% by 2-D echo
* Class I indication for cardiac surgery
* Contraindication for placement of a bioprosthetic valve
* Documented history of cardiac amyloidosis

Primary outcomes:
measure: Composite rate of all-cause mortality, all-stroke, life threatening or fatal bleeding, acute kidney injury, hospitalization due to device or procedure-related complication, or valve dysfunction requiring reintervention.
timeFrame: 30 days
measure: Composite rate of all-cause mortality, heart failure hospitalization or event, or medical instability leading to aortic valve replacement or re-intervention.
timeFrame: 2 years
Secondary outcomes:
measure: Proportion of subjects alive and with moderately improved quality of life (≥ 10 points in KCCQ summary score from baseline)
timeFrame: 1 year
measure: Composite of all-cause mortality and heart failure hospitalizations or events.
timeFrame: 2 years
measure: Composite of all-cause mortality, all-stroke, or unplanned CV hospitalizations
timeFrame: 2 years
measure: Heart failure hospitalizations or events.
timeFrame: 2 years
measure: All-cause mortality
timeFrame: 2 years
measure: Unplanned cardiovascular hospitalizations
timeFrame: 2 years
measure: Days alive and free of unplanned cardiovascular hospitalizations
timeFrame: 2 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham (UAB) Hospital
state: Alabama
city: Phoenix
country: United States
facility: Abrazo Arizone Heart Hospital
state: Arizona
city: Scottsdale
country: United States
facility: HonorHealth Scottsdale Shea Medical Center
state: Arizona
city: Thousand Oaks
country: United States
facility: Los Robles Hospital & Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Bridgeport
country: United States
facility: Saint Vincents Medical Center
state: Connecticut
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
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: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Saint Vincent's Medical Center Riverside
state: Florida
city: Orlando
country: United States
facility: Orlando Health
state: Florida
city: Tallahassee
country: United States
facility: Tallahassee Memorial Hospital
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Louisville
country: United States
facility: Jewish Hospital
state: Kentucky
city: Houma
country: United States
facility: Terrebonne General Medical Center
state: Louisiana
city: Baltimore
country: United States
facility: The Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System - University Hospital
state: Michigan
city: Detroit
country: United States
facility: Ascension Saint John Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health
state: Michigan
city: Minneapolis
country: United States
facility: Abbott Northwestern Hospital
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: SSM Health Saint Louis University Hospital
state: Missouri
city: Manchester
country: United States
facility: Catholic Medical Center
state: New Hampshire
city: Browns Mills
country: United States
facility: Deborah Heart and Lung Center
state: New Jersey
city: Englewood
country: United States
facility: Englewood Hospital & Medical Center
state: New Jersey
city: Manhasset
country: United States
facility: Northwell Health
state: New York
city: New York
country: United States
facility: The Mount Sinai Hospital
state: New York
city: Asheville
country: United States
facility: Mission Hospital
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Heatlh Sciences
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Kettering
country: United States
facility: Kettering Health Main Campus
state: Ohio
city: Oklahoma City
country: United States
facility: Integris Baptist Medical Center
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health & Science University Hospital
state: Oregon
city: Allentown
country: United States
facility: Lehigh Valley Hospital, Inc
state: Pennsylvania
city: Harrisburg
country: United States
facility: UPMC Pinnacle Harrisburg Campus
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Rapid City
country: United States
facility: Monument Health Rapid City Hospital
state: South Dakota
city: Chattanooga
country: United States
facility: Erlanger Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Medical City Dallas
state: Texas
city: Fort Worth
country: United States
facility: Texas Health Harris Methodist Hospital Fort Worth
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: San Antonio
country: United States
facility: Methodist Hospital San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: Intermountain Cardiovascular and Thoracic Surgery
state: Utah
city: Burlington
country: United States
facility: The University of Vermont
state: Vermont
city: Roanoke
country: United States
facility: Carilion Roanoke Memorial Hospital
state: Virginia
city: Spokane
country: United States
facility: Providence Sacred Heart Medical Center & Children's Hospital
state: Washington
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
city: Milwaukee
country: United States
facility: Aurora Saint Lukes Medical Center
state: Wisconsin
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
city: Sankt Pölten
country: Austria
facility: University Hospital Sankt Poelten
city: Wien
country: Austria
facility: Allgemeines Krankenhaus - Universitätskliniken Wien
city: Liège
country: Belgium
facility: CHU de Liege- Hopital du Sart Tilman
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Montréal
country: Canada
facility: Montreal Heart Hospital
state: Quebec
city: Quebec City
country: Canada
facility: Institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ)
state: Quebec
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Centre
city: Rennes
country: France
facility: CHU de Rennes - Hôpital Pontchaillou
state: Brittany
city: Brest
country: France
facility: CHRU Brest - Hôpital de la Cavale Blanche
city: Clermont-Ferrand
country: France
facility: Centre Hospitalier Universitaire de Clermont-Ferrand - Gabriel-Montpied
city: Marseille
country: France
facility: Hôpital de la Timone
city: Paris
country: France
facility: Institut Mutualiste Montsouris
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
city: Toulouse Cedex
country: France
facility: Clinique Pasteur
city: Bad Krozingen
country: Germany
facility: Universitäts-Herzzentrum Freiburg - Bad Krozingen
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
city: Dortmund
country: Germany
facility: Kath Saint Johannes-Gesellschaft Dortmund gGmbH Saint Johannes-Hospital Dortmund
city: Leipzig
country: Germany
facility: Herzzentrum Leipzig GmbH
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes Gutenberg-Universität Mainz
city: München
country: Germany
facility: Klinikum der Universität München - Campus Grosshadern
city: Galway
country: Ireland
facility: Galway University Hospitals - University Hospital Galway (UHG)
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Petah Tikva
country: Israel
facility: Rabin Medical Center- Beilinson Hospital
city: Catania
country: Italy
facility: Presidio Ospedaliero Gaspare Rodolico
city: Milano
country: Italy
facility: Ospedale San Raffaele - Milano
city: San Donato Milanese
country: Italy
facility: IRCCS Policlinico San Donato
city: Kanagawa
country: Japan
facility: Shonan Kamakura General Hospital
state: Kamakura
city: Isehara
country: Japan
facility: Tokai University Hospital
state: Kanagawa
city: Kawasaki
country: Japan
facility: Kawasaki Saiwai Hospital
state: Kanagawa
city: Osaka
country: Japan
facility: Osaka Keisatsu Hospital
city: Osaka
country: Japan
facility: Osaka University Hospital
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Nieuwegein
country: Netherlands
facility: St Antonius Ziekenhuis
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Barcelona
country: Spain
facility: Hospital Universitari Clínic de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Salamanca
country: Spain
facility: Complejo Asistencial Universitario de Salamanca
city: Valladolid
country: Spain
facility: Hospital Clínico Universitario de Valladolid
city: Lund
country: Sweden
facility: Skanes Universitetssjukhus
city: Bern
country: Switzerland
facility: Inselspital - Universitätsspital Bern
city: Belfast
country: United Kingdom
facility: Royal Victoria Hospital - Belfast Health and Social Care Trust
state: U.k.
city: London
country: United Kingdom
facility: Saint Bartholomew's Hospital
Study officials:
affiliation: Allina Health System
name: Paul Sorajja, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fondation IUCPQ
name: Josep Rodes-Cabau, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Inselspital, Universitätsspital Bern
name: Stephan Windecker, Prof.
role: PRINCIPAL_INVESTIGATOR
References: