PROGRESS: Management of Moderate Aortic Stenosis by Clinical Surveillance or TAVR

NCT04889872 | Recruiting DMC FDA Device

• 1 other identifier: 2021-01
• Study Type: interventional
• Target: 2,250
• Locations: 6 countries
• Sites: 80

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.

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

Outcome Measures

Primary Outcomes (2)

• Primary Effectiveness Endpoint

  Non-hierarchical composite of death, and heart failure hospitalization or event

  2 years

• Primary Safety Endpoint

  Non-hierarchical composite of death, stroke, life threatening or fatal bleeding, acute kidney injury stage 4, hospitalization due to device- or procedure-related complication, and valve dysfunction requiring reintervention

  30 days

Secondary Outcomes (5)

• Death, stroke, or heart failure hospitalization

  2 years

• Alive and Kansas City Cardiomyopathy Questionnaire (KCCQ) score improvement ≥10 points from baseline sustained through 2 years

  2 years

• Heart failure hospitalization

  2 years

• Left ventricle (LV) mass index

  2 years

• Diastolic dysfunction ≥ Grade 2

  2 years

Study Arms (2)

TAVR

EXPERIMENTAL

Transcatheter Aortic Valve Replacement (TAVR)

Device: SAPIEN 3 / SAPIEN 3 Ultra / SAPIEN 3 Ultra RESILIA

CS

NO INTERVENTION

Clinical Surveillance (CS)

Interventions

SAPIEN 3 / SAPIEN 3 Ultra / SAPIEN 3 Ultra RESILIA DEVICE

Patients will be implanted with a SAPIEN 3 / SAPIEN 3 Ultra / SAPIEN 3 Ultra RESILIA heart valve

TAVR

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• years of age or older at time of randomization
• Moderate aortic stenosis
• Subject has symptoms or evidence of cardiac damage/dysfunction
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Edwards Lifesciences: lead

Study Sites (80)

Heart Center LLC, Huntsville

Huntsville, Alabama, 35801, United States

RECRUITING

Tucson Medical Center

Tucson, Arizona, 85712, United States

ACTIVE NOT RECRUITING

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

RECRUITING

Huntington Hospital

Pasadena, California, 91105, United States

WITHDRAWN

Eisenhower Desert Cardiology Center

Rancho Mirage, California, 92270, United States

RECRUITING

Bay Area Structural Heart at Sutter Health

San Francisco, California, 94109, United States

RECRUITING

Kaiser San Francisco Medical Center

San Francisco, California, 94118, United States

ACTIVE NOT RECRUITING

University of California San Francisco

San Francisco, California, 94143, United States

RECRUITING

Santa Barbara Cottage Hospital

Santa Barbara, California, 93105, United States

RECRUITING

Stanford Univeristy

Stanford, California, 94305, United States

RECRUITING

UC Health Medical Center of the Rockies

Loveland, Colorado, 80538, United States

RECRUITING

Yale Universtiy

New Haven, Connecticut, 06510, United States

RECRUITING

The Cardiac & Vascular Institute Research Foundation

Gainesville, Florida, 32605, United States

WITHDRAWN

Baptist Health Research Center

Jacksonville, Florida, 32207, United States

RECRUITING

Sarasota Memorial Health Care System

Sarasota, Florida, 34239, United States

RECRUITING

Emory University Atlanta

Atlanta, Georgia, 30308, United States

RECRUITING

Piedmont Heart Institute

Atlanta, Georgia, 30309, United States

RECRUITING

Saint Alphonsus

Boise, Idaho, 83704, United States

RECRUITING

Rush University Medical Center

Chicago, Illinois, 60612, United States

RECRUITING

Alexian Brothers Hospital

Lisle, Illinois, 60532, United States

RECRUITING

Ascension Via Christi St. Francis

Wichita, Kansas, 67226, United States

RECRUITING

Louisiana State University

New Orleans, Louisiana, 70112, United States

RECRUITING

Ochsner Clinical Foundation

New Orleans, Louisiana, 70121, United States

ACTIVE NOT RECRUITING

Massachusetts General Hospital Boston

Boston, Massachusetts, 02114, United States

RECRUITING

Minneapolis Heart Institue, St. Paul's

Minneapolis, Minnesota, 55102, United States

RECRUITING

CentraCare Heart and Vascular Center

Saint Cloud, Minnesota, 56303, United States

RECRUITING

Saint Luke's Hospital of Kansas City Mid America

Kansas City, Missouri, 64111, United States

RECRUITING

St. Patrick Hospital

Missoula, Montana, 59802, United States

ACTIVE NOT RECRUITING

Mary Hitchcock Memorial Hospital

Lebanon, New Hampshire, 03756, United States

RECRUITING

Atlantic Health System Hospital Corp - Morristown Medical Center

Morristown, New Jersey, 07960, United States

RECRUITING

Jersey Shore University Medical Center

Neptune City, New Jersey, 07753, United States

RECRUITING

Rutgers Robert Wood Johnson Medical School

New Brunswick, New Jersey, 08901, United States

RECRUITING

The Valley Hospital

Ridgewood, New Jersey, 07450, United States

RECRUITING

University of Buffalo Kaleida Health

Buffalo, New York, 14203, United States

RECRUITING

NYU Langone Hospital - Long Island

Mineola, New York, 11501, United States

RECRUITING

NYU Langone Health

New York, New York, 10016, United States

WITHDRAWN

Columbia University Irving Medical Center/NYPH

New York, New York, 10032, United States

ACTIVE NOT RECRUITING

Rochester General Hospital

Rochester, New York, 14621, United States

RECRUITING

St. Francis Hospital

Roslyn, New York, 11576, United States

RECRUITING

Montefiore Medical Center

The Bronx, New York, 10467, United States

RECRUITING

Moses Cone Memorial Hospital

Greensboro, North Carolina, 27401, United States

RECRUITING

The Christ Hospital

Cincinnati, Ohio, 45219, United States

ACTIVE NOT RECRUITING

Mount Carmel Health System

Columbus, Ohio, 43213, United States

ACTIVE NOT RECRUITING

Oklahoma Heart Institute

Tulsa, Oklahoma, 74104, United States

RECRUITING

Kaiser Permanente Northwest

Clackamas, Oregon, 97015, United States

ACTIVE NOT RECRUITING

Providence Heart & Vascular Institute Portland

Portland, Oregon, 97225, United States

WITHDRAWN

Legacy Emanuel Medical Center

Portland, Oregon, 97227, United States

RECRUITING

Allegheny Singer Research Institute

Pittsburgh, Pennsylvania, 15212, United States

RECRUITING

UPMC Presbyterian Shadyside

Pittsburgh, Pennsylvania, 15213, United States

ACTIVE NOT RECRUITING

Pinnacle Health Harrisburg

Wormleysburg, Pennsylvania, 17043, United States

ACTIVE NOT RECRUITING

Lankenau Medical Center

Wynnewood, Pennsylvania, 19096, United States

RECRUITING

Baptist Memorial Hospital Memphis

Germantown, Tennessee, 38138, United States

RECRUITING

Methodist Le Bonheur Healthcare

Germantown, Tennessee, 38138, United States

RECRUITING

Parkwest Medical Center

Knoxville, Tennessee, 37923, United States

RECRUITING

Saint Thomas Health

Nashville, Tennessee, 37205, United States

RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

RECRUITING

Ascension Texas Cardiovascular

Austin, Texas, 78705, United States

RECRUITING

UT Southwestern Medical Center

Dallas, Texas, 75235, United States

RECRUITING

HCA Houston Healthcare Medical Center

Houston, Texas, 77004, United States

RECRUITING

The University of Texas Health Science Center

Houston, Texas, 77030, United States

RECRUITING

The Heart Hospital Baylor Plano

Plano, Texas, 75093, United States

RECRUITING

Methodist Hospital of San Antonio

San Antonio, Texas, 78229, United States

ACTIVE NOT RECRUITING

Kaiser Mid Atlantic

McLean, Virginia, 22102, United States

RECRUITING

Sentara Norfolk General Hospital

Norfolk, Virginia, 23507, United States

RECRUITING

Swedish Medical Center

Seattle, Washington, 98112, United States

RECRUITING

The Prince Charles Hospital

Chermside, Queensland, 4032, Australia

ACTIVE NOT RECRUITING

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

ACTIVE NOT RECRUITING

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

ACTIVE NOT RECRUITING

Monash Health

Clayton, Victoria, 3168, Australia

ACTIVE NOT RECRUITING

St. Paul's Hospital

Vancouver, British Columbia, V6E1M7, Canada

ACTIVE NOT RECRUITING

Hamiton Health Services

Hamilton, Onterio, L8L 2X2, Canada

ACTIVE NOT RECRUITING

Kokura Memorial Hospital

Fukuoka, Kyushu, 802-8555, Japan

ACTIVE NOT RECRUITING

Sendai Kousei Hospital

Sendai, Miyagi, 981-0914, Japan

ACTIVE NOT RECRUITING

Sakakibara Heart Institute

Fuchū, Tokyo, 183-0003, Japan

ACTIVE NOT RECRUITING

Keio University Hospital

Shinjuku, Tokyo, 160-8582, Japan

ACTIVE NOT RECRUITING

AMC Amsterdam

Amsterdam, North Holland, 1105 AZ, Netherlands

ACTIVE NOT RECRUITING

Leiden Universitair Medisch Centrum

Leiden, South Holland, 2333, Netherlands

ACTIVE NOT RECRUITING

Erasmus Rotterdam

Rotterdam, South Holland, 3015, Netherlands

ACTIVE NOT RECRUITING

Hôpitaux Universitaire de Genève

Geneva, 1205, Switzerland

ACTIVE NOT RECRUITING

Universitätsspital Zürich

Zurich, 8091, Switzerland

WITHDRAWN

Related Publications (1)

• Genereux P, Makkar R, Bax JJ, Pibarot P, Lindman BR, Prince H, Park B, Cohen DJ, Mack MJ, Leon MB. Design and rationale of the prospective, randomized, controlled trial to assess the management of moderate aortic stenosis by clinical surveillance or transcatheter aortic valve replacement: The PROGRESS Trial. Am Heart J. 2026 Mar 25:107433. doi: 10.1016/j.ahj.2026.107433. Online ahead of print.

  PMID: 41895563 DERIVED

MeSH Terms

Conditions

Aortic Valve, Calcification of; Aortic Valve Stenosis

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction

Study Officials

• Philippe Généreux, MD

  Morristown Medical Center, Morristown, NJ, USA

  PRINCIPAL INVESTIGATOR

• Jeroen J Bax, MD, PhD

  Leiden University Medical Center, Leiden, The Netherlands

  PRINCIPAL INVESTIGATOR

• Raj Makkar, MD

  Cedars-Sinai Medical Center, Los Angeles, CA, USA

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Edwards THV Clinical Affairs

CONTACT

949-250-2500; THV_CT.gov@Edwards.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2021
• First Posted: May 17, 2021
• Study Start: October 12, 2021
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2037
• Last Updated: December 17, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

NL (3); CH (2); US (65); AU (4); CA (2); JP (4)