Aortic Stenosis, CalcificPROGRESSNCT04889872
PROGRESS: Management of Moderate Aortic Stenosis by Clinical Surveillance or TAVR
A study testing SAPIEN 3 / SAPIEN 3 Ultra / SAPIEN 3 Ultra RESILIA in people with Aortic Stenosis, Calcific and Aortic Valve Stenosis, run by Edwards Lifesciences at 80 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Aortic Stenosis, Calcific, Aortic Valve Stenosis
- What is being tested?
- SAPIEN 3 / SAPIEN 3 Ultra / SAPIEN 3 Ultra RESILIA
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,250 participants
- Where
- 80 sitesin 6 countries
- Study dates
- 12 Oct 2021to Jun 2037
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 65 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.
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
80 sites in 6 countries. Contact the study team or a site near you to ask about taking part.
80 sites in 6 countries
United States65 sites, 50 recruiting
- Recruiting
Emory University Atlanta
Atlanta, Georgia, 30308
- Recruiting
Piedmont Heart Institute
Atlanta, Georgia, 30309
- Recruiting
Ascension Texas Cardiovascular
Austin, Texas, 78705
- Recruiting
Saint Alphonsus
Boise, Idaho, 83704
- Recruiting
Massachusetts General Hospital Boston
Boston, Massachusetts, 02114
- Recruiting
University of Buffalo Kaleida Health
Buffalo, New York, 14203
- Recruiting
Rush University Medical Center
Chicago, Illinois, 60612
- Active, not recruiting
The Christ Hospital
Cincinnati, Ohio, 45219
- Active, not recruiting
Kaiser Permanente Northwest
Clackamas, Oregon, 97015
- Active, not recruiting
Mount Carmel Health System
Columbus, Ohio, 43213
- Recruiting
UT Southwestern Medical Center
Dallas, Texas, 75235
- Withdrawn
The Cardiac & Vascular Institute Research Foundation
Gainesville, Florida, 32605
- Recruiting
Baptist Memorial Hospital Memphis
Germantown, Tennessee, 38138
- Recruiting
Methodist Le Bonheur Healthcare
Germantown, Tennessee, 38138
- Recruiting
Moses Cone Memorial Hospital
Greensboro, North Carolina, 27401
- Recruiting
HCA Houston Healthcare Medical Center
Houston, Texas, 77004
- Recruiting
The University of Texas Health Science Center
Houston, Texas, 77030
- Recruiting
Heart Center LLC, Huntsville
Huntsville, Alabama, 35801
- Recruiting
Baptist Health Research Center
Jacksonville, Florida, 32207
- Recruiting
Saint Luke's Hospital of Kansas City Mid America
Kansas City, Missouri, 64111
- Recruiting
Parkwest Medical Center
Knoxville, Tennessee, 37923
- Recruiting
Mary Hitchcock Memorial Hospital
Lebanon, New Hampshire, 03756
- Recruiting
Alexian Brothers Hospital
Lisle, Illinois, 60532
- Recruiting
Cedars-Sinai Medical Center
Los Angeles, California, 90048
- Recruiting
UC Health Medical Center of the Rockies
Loveland, Colorado, 80538
- Recruiting
Kaiser Mid Atlantic
McLean, Virginia, 22102
- Recruiting
NYU Langone Hospital - Long Island
Mineola, New York, 11501
- Recruiting
Minneapolis Heart Institue, St. Paul's
Minneapolis, Minnesota, 55102
- Active, not recruiting
St. Patrick Hospital
Missoula, Montana, 59802
- Recruiting
Atlantic Health System Hospital Corp - Morristown Medical Center
Morristown, New Jersey, 07960
- Recruiting
Saint Thomas Health
Nashville, Tennessee, 37205
- Recruiting
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
- Recruiting
Jersey Shore University Medical Center
Neptune City, New Jersey, 07753
- Recruiting
Rutgers Robert Wood Johnson Medical School
New Brunswick, New Jersey, 08901
- Recruiting
Yale Universtiy
New Haven, Connecticut, 06510
- Recruiting
Louisiana State University
New Orleans, Louisiana, 70112
- Active, not recruiting
Ochsner Clinical Foundation
New Orleans, Louisiana, 70121
- Withdrawn
NYU Langone Health
New York, New York, 10016
- Active, not recruiting
Columbia University Irving Medical Center/NYPH
New York, New York, 10032
- Recruiting
Sentara Norfolk General Hospital
Norfolk, Virginia, 23507
- Withdrawn
Huntington Hospital
Pasadena, California, 91105
- Recruiting
Allegheny Singer Research Institute
Pittsburgh, Pennsylvania, 15212
- Active, not recruiting
UPMC Presbyterian Shadyside
Pittsburgh, Pennsylvania, 15213
- Recruiting
The Heart Hospital Baylor Plano
Plano, Texas, 75093
- Withdrawn
Providence Heart & Vascular Institute Portland
Portland, Oregon, 97225
- Recruiting
Legacy Emanuel Medical Center
Portland, Oregon, 97227
- Recruiting
Eisenhower Desert Cardiology Center
Rancho Mirage, California, 92270
- Recruiting
The Valley Hospital
Ridgewood, New Jersey, 07450
- Recruiting
Rochester General Hospital
Rochester, New York, 14621
- Recruiting
St. Francis Hospital
Roslyn, New York, 11576
- Recruiting
CentraCare Heart and Vascular Center
Saint Cloud, Minnesota, 56303
- Active, not recruiting
Methodist Hospital of San Antonio
San Antonio, Texas, 78229
- Recruiting
Bay Area Structural Heart at Sutter Health
San Francisco, California, 94109
- Active, not recruiting
Kaiser San Francisco Medical Center
San Francisco, California, 94118
- Recruiting
University of California San Francisco
San Francisco, California, 94143
- Recruiting
Santa Barbara Cottage Hospital
Santa Barbara, California, 93105
- Recruiting
Sarasota Memorial Health Care System
Sarasota, Florida, 34239
- Recruiting
Swedish Medical Center
Seattle, Washington, 98112
- Recruiting
Stanford Univeristy
Stanford, California, 94305
- Recruiting
Montefiore Medical Center
The Bronx, New York, 10467
- Active, not recruiting
Tucson Medical Center
Tucson, Arizona, 85712
- Recruiting
Oklahoma Heart Institute
Tulsa, Oklahoma, 74104
- Recruiting
Ascension Via Christi St. Francis
Wichita, Kansas, 67226
- Active, not recruiting
Pinnacle Health Harrisburg
Wormleysburg, Pennsylvania, 17043
- Recruiting
Lankenau Medical Center
Wynnewood, Pennsylvania, 19096
Australia4 sites
- Active, not recruiting
Royal Adelaide Hospital
Adelaide, South Australia, 5000
- Active, not recruiting
Flinders Medical Centre
Bedford Park, South Australia, 5042
- Active, not recruiting
The Prince Charles Hospital
Chermside, Queensland, 4032
- Active, not recruiting
Monash Health
Clayton, Victoria, 3168
Japan4 sites
- Active, not recruiting
Sakakibara Heart Institute
Fuchū, Tokyo, 183-0003
- Active, not recruiting
Kokura Memorial Hospital
Fukuoka, Kyushu, 802-8555
- Active, not recruiting
Sendai Kousei Hospital
Sendai, Miyagi, 981-0914
- Active, not recruiting
Keio University Hospital
Shinjuku, Tokyo, 160-8582
Netherlands3 sites
- Active, not recruiting
AMC Amsterdam
Amsterdam, North Holland, 1105 AZ
- Active, not recruiting
Leiden Universitair Medisch Centrum
Leiden, South Holland, 2333
- Active, not recruiting
Erasmus Rotterdam
Rotterdam, South Holland, 3015
Canada2 sites
- Active, not recruiting
Hamiton Health Services
Hamilton, Onterio, L8L 2X2
- Active, not recruiting
St. Paul's Hospital
Vancouver, British Columbia, V6E1M7
Switzerland2 sites
- Active, not recruiting
Hôpitaux Universitaire de Genève
Geneva, 1205
- Withdrawn
Universitätsspital Zürich
Zurich, 8091
About this study
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
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.
Read the 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.
- Conditions
- Aortic Stenosis, Calcific, Aortic Valve Stenosis
- Being tested
- SAPIEN 3 / SAPIEN 3 Ultra / SAPIEN 3 Ultra RESILIA
- Keywords
- Transcatheter aortic valve replacement (TAVR), SAPIEN 3, SAPIEN 3 Ultra, SAPIEN 3 Ultra RESILIA, Moderate aortic stenosis, Aortic stenosis, Transcatheter heart valve
- Medical subject headings
- Aortic Valve, Calcification of, Aortic Valve Stenosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SAPIEN 3 / SAPIEN 3 Ultra / SAPIEN 3 Ultra RESILIADevice
Patients will be implanted with a SAPIEN 3 / SAPIEN 3 Ultra / SAPIEN 3 Ultra RESILIA heart valve
| Study group | Role | What they receive |
|---|---|---|
| TAVR | Experimental | Transcatheter Aortic Valve Replacement (TAVR) Receives: Device: SAPIEN 3 / SAPIEN 3 Ultra / SAPIEN 3 Ultra RESILIA |
| CS | No intervention | Clinical Surveillance (CS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Effectiveness Endpoint
Non-hierarchical composite of death, and heart failure hospitalization or event
Measured: 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
Measured: 30 days
Secondary outcomes (5)
Death, stroke, or heart failure hospitalization
The number of patients that had this event
Measured: 2 years
Alive and Kansas City Cardiomyopathy Questionnaire (KCCQ) score improvement ≥10 points from baseline sustained through 2 years
The number of patients that met all these criteria
Measured: 2 years
Heart failure hospitalization
The number of patients that had this event
Measured: 2 years
Left ventricle (LV) mass index
Echocardiographic measurement of the size of the left ventricle
Measured: 2 years
Diastolic dysfunction ≥ Grade 2
Echocardiographic measurement of the stiffness of the left ventricle.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2021
- Study start12 Oct 2021
- Primary completionJun 2029 (estimated)
- Study completionJun 2037 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Aortic Stenosis, CalcificStudies of the same condition, open and under way.
- More trials run by Edwards LifesciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2,250 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Edwards Lifesciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Philippe Généreux, MD, Principal investigator, Morristown Medical Center, Morristown, NJ, USAJeroen J Bax, MD, PhD, Principal investigator, Leiden University Medical Center, Leiden, The NetherlandsRaj Makkar, MD, Principal investigator, Cedars-Sinai Medical Center, Los Angeles, CA, USA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04889872
- Sponsor's protocol ID
- 2021-01
- Acronym
- PROGRESS
- Status last verified
- Oct 2025
- First submitted
- 12 May 2021
- Last updated
- 17 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Genereux P, Makkar RR, 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 Jul;297:107433. doi: 10.1016/j.ahj.2026.107433. Epub 2026 Mar 25.
PubMed 41895563
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04889872
- Acronym / sponsor ID
- PROGRESS / 2021-01
- 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
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 2,250 participants (estimated)
- Lead sponsor
- Edwards LifesciencesIndustry (pharma, biotech, devices)
- Study start
- 12 Oct 2021 (actual)
- Primary completion
- Jun 2029 (estimated)
- Study completion
- Jun 2037 (estimated)
- First posted
- 17 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TAVR | Experimental | Device: SAPIEN 3 / SAPIEN 3 Ultra / SAPIEN 3 Ultra RESILIATranscatheter Aortic Valve Replacement (TAVR) |
| CS | No intervention | –Clinical Surveillance (CS) |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (4 listed)
- 65 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.
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SAPIEN 3 / SAPIEN 3 Ultra / SAPIEN 3 Ultra RESILIAPatients will be implanted with a SAPIEN 3 / SAPIEN 3 Ultra / SAPIEN 3 Ultra RESILIA heart valve | Device | TAVR |
Primary outcome
Primary Effectiveness Endpoint
Time frame: 2 years
Non-hierarchical composite of death, and heart failure hospitalization or event
Primary Safety Endpoint
Time frame: 30 days
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
5 secondary outcomes
Death, stroke, or heart failure hospitalization
Time frame: 2 years
Alive and Kansas City Cardiomyopathy Questionnaire (KCCQ) score improvement ≥10 points from baseline sustained through 2 years
Time frame: 2 years
Heart failure hospitalization
Time frame: 2 years
Left ventricle (LV) mass index
Time frame: 2 years
Diastolic dysfunction ≥ Grade 2
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2025.
- Derived from this study: PubMed 41895563Genereux P, Makkar RR, 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 Jul;297:107433. doi: 10.1016/j.ahj.2026.107433. Epub 2026 Mar 25.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Philippe Généreux, MD principal investigator
Morristown Medical Center, Morristown, NJ, USA
Jeroen J Bax, MD, PhD principal investigator
Leiden University Medical Center, Leiden, The Netherlands
Raj Makkar, MD principal investigator
Cedars-Sinai Medical Center, Los Angeles, CA, USA
80 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing SAPIEN 3 / SAPIEN 3 Ultra / SAPIEN 3 Ultra RESILIA in people with Aortic Stenosis, Calcific and Aortic Valve Stenosis, run by Edwards Lifesciences at 80 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 80 sites in United States, Australia, Japan, Netherlands, Canada and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Edwards THV Clinical Affairs (949-250-2500, THV_CT.gov@Edwards.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary Effectiveness Endpoint (time frame: 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04889872, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2025; AzTrials last refreshed its copy on 26 Oct 2026.