Clinical trial NCT04889872: PROGRESS: Management of Moderate Aortic Stenosis by Clinical Surveillance or TAVR
Official title: The PROGRESS Trial: A Prospective, Randomized, Controlled Trial to Assess the Management of Moderate Aortic Stenosis by Clinical Surveillance or Transcatheter Aortic Valve Replacement
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Aortic Stenosis, Calcific
Aortic Valve Stenosis
Keywords: Transcatheter aortic valve replacement (TAVR)
SAPIEN 3
SAPIEN 3 Ultra
SAPIEN 3 Ultra RESILIA
Moderate aortic stenosis
Aortic stenosis
Transcatheter heart valve
Lead sponsor: Edwards Lifesciences
Sponsor class: INDUSTRY
First posted: 2021-05-17
Enrollment: 2250
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study objective is to establish the safety and effectiveness of the Edwards SAPIEN 3 / SAPIEN 3 Ultra / SAPIEN 3 Ultra RESILIA Transcatheter Heart Valve systems in subjects with moderate, calcific aortic stenosis.

Following completion of enrollment, subjects will be eligible for enrollment in the continued access phase of the trial.

Detailed description: This is a prospective, randomized, controlled, multicenter study. Subjects will be randomized to either transcatheter aortic valve replacement (TAVR) with the SAPIEN 3 / SAPIEN 3 Ultra /SAPIEN 3 Ultra RESILIA THV or Clinical Surveillance.

Eligibility criteria: Key Inclusion Criteria:

1. 65 years of age or older at time of randomization
2. Moderate aortic stenosis
3. Subject has symptoms or evidence of cardiac damage/dysfunction
4. The subject or subject's legal representative has been informed of the nature of the study, agrees to its provisions, and has provided written informed consent.

Key Exclusion Criteria:

1. Native aortic annulus size unsuitable for the THV
2. Anatomical characteristics that would preclude safe transfemoral placement of the introducer sheath or safe passage of the delivery system
3. Aortic valve is unicuspid or non-calcified
4. Bicuspid aortic valve with an aneurysmal ascending aorta \> 4.5 cm or severe raphe/leaflet calcification
5. Pre-existing mechanical or bioprosthetic aortic valve
6. Severe aortic regurgitation
7. Prior balloon aortic valvuloplasty to treat severe AS
8. LVEF \< 20%
9. Left ventricular outflow tract calcification that would increase the risk of annular rupture or significant paravalvular leak post-TAVR
10. Cardiac imaging evidence of intracardiac mass, thrombus, or vegetation
11. Coronary or aortic valve anatomy that increases the risk of coronary artery obstruction post-TAVR

Primary outcomes:
measure: Primary Effectiveness Endpoint
timeFrame: 2 years
measure: Primary Safety Endpoint
timeFrame: 30 days
Secondary outcomes:
measure: Death, stroke, or unplanned cardiovascular hospitalization
timeFrame: 2 years
measure: Death, unplanned cardiovascular hospitalization, or decrease of > 10 points in Kansas City Cardiomyopathy Questionnaire (KCCQ)
timeFrame: 2 years
measure: Unplanned cardiovascular hospitalization
timeFrame: 2 years
measure: Left ventricle (LV) mass index
timeFrame: 2 years
measure: Stroke volume index
timeFrame: 2 years
measure: Diastolic dysfunction ≥ Grade 2
timeFrame: 2 years
measure: N-Terminal Pro B-type Natriuretic Peptide (NT-ProBNP)
timeFrame: 2 years
measure: KCCQ overall score
timeFrame: 2 years
measure: Reduction in LVEF ≥ 5% from baseline AND LVEF < 60%
timeFrame: 2 years
measure: New onset atrial fibrillation
timeFrame: 2 years
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Heart Center LLC, Huntsville
state: Alabama
city: Tucson
country: United States
facility: Tucson Medical Center
state: Arizona
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Pasadena
country: United States
facility: Huntington Hospital
state: California
city: Rancho Mirage
country: United States
facility: Eisenhower Desert Cardiology Center
state: California
city: San Francisco
country: United States
facility: Bay Area Structural Heart at Sutter Health
state: California
city: San Francisco
country: United States
facility: Kaiser San Francisco Medical Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Santa Barbara
country: United States
facility: Santa Barbara Cottage Hospital
state: California
city: Stanford
country: United States
facility: Stanford Univeristy
state: California
city: Loveland
country: United States
facility: UC Health Medical Center of the Rockies
state: Colorado
city: New Haven
country: United States
facility: Yale Universtiy
state: Connecticut
city: Gainesville
country: United States
facility: The Cardiac & Vascular Institute Research Foundation
state: Florida
city: Jacksonville
country: United States
facility: Baptist Health Research Center
state: Florida
city: Sarasota
country: United States
facility: Sarasota Memorial Health Care System
state: Florida
city: Atlanta
country: United States
facility: Emory University Atlanta
state: Georgia
city: Atlanta
country: United States
facility: Piedmont Heart Institute
state: Georgia
city: Boise
country: United States
facility: Saint Alphonsus
state: Idaho
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Lisle
country: United States
facility: Alexian Brothers Hospital
state: Illinois
city: Wichita
country: United States
facility: Ascension Via Christi St. Francis
state: Kansas
city: New Orleans
country: United States
facility: Louisiana State University
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Clinical Foundation
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital Boston
state: Massachusetts
city: Minneapolis
country: United States
facility: Minneapolis Heart Institue, St. Paul's
state: Minnesota
city: Saint Cloud
country: United States
facility: CentraCare Heart and Vascular Center
state: Minnesota
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City Mid America
state: Missouri
city: Missoula
country: United States
facility: St. Patrick Hospital
state: Montana
city: Lebanon
country: United States
facility: Mary Hitchcock Memorial Hospital
state: New Hampshire
city: Morristown
country: United States
facility: Atlantic Health System Hospital Corp - Morristown Medical Center
state: New Jersey
city: Neptune
country: United States
facility: Jersey Shore University Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Robert Wood Johnson Medical School
state: New Jersey
city: Ridgewood
country: United States
facility: The Valley Hospital
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Buffalo
country: United States
facility: University of Buffalo Kaleida Health
state: New York
city: Mineola
country: United States
facility: NYU Langone Hospital - Long Island
state: New York
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center/NYPH
state: New York
city: Rochester
country: United States
facility: Rochester General Hospital
state: New York
city: Roslyn
country: United States
facility: St. Francis Hospital
state: New York
city: Greensboro
country: United States
facility: Moses Cone Memorial Hospital
state: North Carolina
city: Cincinnati
country: United States
facility: The Christ Hospital
state: Ohio
city: Columbus
country: United States
facility: Mount Carmel Health System
state: Ohio
city: Tulsa
country: United States
facility: Oklahoma Heart Institute
state: Oklahoma
city: Clackamas
country: United States
facility: Kaiser Permanente Northwest
state: Oregon
city: Portland
country: United States
facility: Providence Heart & Vascular Institute Portland
state: Oregon
city: Portland
country: United States
facility: Legacy Emanuel Medical Center
state: Oregon
city: Pittsburgh
country: United States
facility: Allegheny Singer Research Institute
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Presbyterian Shadyside
state: Pennsylvania
city: Wormleysburg
country: United States
facility: Pinnacle Health Harrisburg
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Medical Center
state: Pennsylvania
city: Germantown
country: United States
facility: Baptist Memorial Hospital Memphis
state: Tennessee
city: Germantown
country: United States
facility: Methodist Le Bonheur Healthcare
state: Tennessee
city: Knoxville
country: United States
facility: Parkwest Medical Center
state: Tennessee
city: Nashville
country: United States
facility: Saint Thomas Health
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Austin
country: United States
facility: Ascension Texas Cardiovascular
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: HCA Houston Healthcare Medical Center
state: Texas
city: Houston
country: United States
facility: The University of Texas Health Science Center
state: Texas
city: Plano
country: United States
facility: The Heart Hospital Baylor Plano
state: Texas
city: San Antonio
country: United States
facility: Methodist Hospital of San Antonio
state: Texas
city: McLean
country: United States
facility: Kaiser Mid Atlantic
state: Virginia
city: Norfolk
country: United States
facility: Sentara Norfolk General Hospital
state: Virginia
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Chermside
country: Australia
facility: The Prince Charles Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Hamilton
country: Canada
facility: Hamiton Health Services
state: Onterio
city: Fukuoka
country: Japan
facility: Kokura Memorial Hospital
state: Kyushu
city: Sendai
country: Japan
facility: Sendai Kousei Hospital
state: Miyagi
city: Fuchu
country: Japan
facility: Sakakibara Heart Institute
state: Tokyo
city: Shinjuku
country: Japan
facility: Keio University Hospital
state: Tokyo
city: Amsterdam
country: Netherlands
facility: AMC Amsterdam
state: North Holland
city: Leiden
country: Netherlands
facility: Leiden Universitair Medisch Centrum
state: South Holland
city: Rotterdam
country: Netherlands
facility: Erasmus Rotterdam
state: South Holland
city: Geneva
country: Switzerland
facility: Hôpitaux Universitaire de Genève
city: Zürich
country: Switzerland
facility: Universitätsspital Zürich
Study officials:
affiliation: Morristown Medical Center, Morristown, NJ, USA
name: Philippe Généreux, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Leiden University Medical Center, Leiden, The Netherlands
name: Jeroen J Bax, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cedars-Sinai Medical Center, Los Angeles, CA, USA
name: Raj Makkar, MD
role: PRINCIPAL_INVESTIGATOR
References: