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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Aortic Valve Stenosis; Aortic Stenosis, Calcific
• Intervention / Treatment: Device: SAPIEN 3 / SAPIEN 3 Ultra / SAPIEN 3 Ultra RESILIA

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 Type: Interventional
• Enrollment (Actual): 1294
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Edwards THV Clinical Affairs; Phone Number: 949-250-2500; Email: THV_CT.gov@Edwards.com

Study Locations

• Australia
  • Queensland
    • Chermside, Queensland, Australia, 4032
      • The Prince Charles Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
    • Bedford Park, South Australia, Australia, 5042
      • Flinders Medical Centre
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Health
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6E1M7
      • St. Paul's Hospital
  • Onterio
    • Hamilton, Onterio, Canada, L8L 2X2
      • Hamiton Health Services
• Japan
  • Kyushu
    • Fukuoka, Kyushu, Japan, 802-8555
      • Kokura Memorial Hospital
  • Miyagi
    • Sendai, Miyagi, Japan, 980-0873
      • Sendai Kousei Hospital
  • Tokyo
    • Fuchu, Tokyo, Japan, 183-0003
      • Sakakibara Heart Institute
    • Shinjuku, Tokyo, Japan, 160-8582
      • Keio University Hospital
• Netherlands
  • North Holland
    • Amsterdam, North Holland, Netherlands, 1105 AZ
      • AMC Amsterdam
  • South Holland
    • Leiden, South Holland, Netherlands, 2333
      • Leiden Universitair Medisch Centrum
    • Rotterdam, South Holland, Netherlands, 3015
      • Erasmus Rotterdam
• Switzerland
  • Geneva, Switzerland, 1205
    • Hôpitaux Universitaire de Genève
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Heart Center LLC, Huntsville
  • Arizona
    • Tucson, Arizona, United States, 85712
      • Tucson Medical Center
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Rancho Mirage, California, United States, 92270
      • Eisenhower Desert Cardiology Center
    • San Francisco, California, United States, 94143
      • University of California San Francisco
    • San Francisco, California, United States, 94109
      • Bay Area Structural Heart at Sutter Health
    • San Francisco, California, United States, 94118
      • Kaiser San Francisco Medical Center
    • Santa Barbara, California, United States, 93105
      • Santa Barbara Cottage Hospital
    • Stanford, California, United States, 94305
      • Stanford Univeristy
  • Colorado
    • Loveland, Colorado, United States, 80538
      • UC Health Medical Center of the Rockies
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale Universtiy
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Baptist Health Research Center
    • Sarasota, Florida, United States, 34239
      • Sarasota Memorial Health Care System
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Heart Institute
    • Atlanta, Georgia, United States, 30308
      • Emory University Atlanta
  • Idaho
    • Boise, Idaho, United States, 83704
      • Saint Alphonsus
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Lisle, Illinois, United States, 60532
      • Alexian Brothers Hospital
  • Kansas
    • Wichita, Kansas, United States, 67226
      • Cardiovascular Research Institute of Kansas
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Louisiana State University
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinical Foundation
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Boston
  • Minnesota
    • Minneapolis, Minnesota, United States, 55102
      • Minneapolis Heart Institue, St. Paul's
    • Saint Cloud, Minnesota, United States, 56303
      • CentraCare Heart and Vascular Center
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Hospital of Kansas City Mid America
  • Montana
    • Missoula, Montana, United States, 59802
      • St. Patrick Hospital
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Mary Hitchcock Memorial Hospital
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Atlantic Health System Hospital Corp - Morristown Medical Center
    • Neptune, New Jersey, United States, 07753
      • Jersey Shore University Medical Center
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers Robert Wood Johnson Medical School
    • Ridgewood, New Jersey, United States, 07450
      • The Valley Hospital
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • Buffalo, New York, United States, 14203
      • University of Buffalo Kaleida Health
    • Mineola, New York, United States, 11501
      • NYU Langone Hospital - Long Island
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center/NYPH
    • Rochester, New York, United States, 14621
      • Rochester General Hospital
    • Roslyn, New York, United States, 11576
      • St. Francis Hospital
  • North Carolina
    • Greensboro, North Carolina, United States, 27401
      • Moses Cone Memorial Hospital
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • The Christ Hospital
    • Columbus, Ohio, United States, 43213
      • Mount Carmel Health System
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74104
      • Oklahoma Heart Institute
  • Oregon
    • Clackamas, Oregon, United States, 97015
      • Kaiser Permanente Northwest
    • Portland, Oregon, United States, 97227
      • Legacy Emanuel Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny Singer Research Institute
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Presbyterian Shadyside
    • Wormleysburg, Pennsylvania, United States, 17043
      • Pinnacle Health Harrisburg
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Medical Center
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Methodist Le Bonheur Healthcare
    • Germantown, Tennessee, United States, 38138
      • Baptist Memorial Hospital Memphis
    • Knoxville, Tennessee, United States, 37923
      • Parkwest Medical Center
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
    • Nashville, Tennessee, United States, 37205
      • Saint Thomas Health
  • Texas
    • Austin, Texas, United States, 78705
      • Ascension Texas Cardiovascular
    • Dallas, Texas, United States, 75235
      • UT Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center
    • Houston, Texas, United States, 77004
      • HCA Houston Healthcare Medical Center
    • Plano, Texas, United States, 75093
      • The Heart Hospital Baylor Plano
    • San Antonio, Texas, United States, 78229
      • Methodist Hospital of San Antonio
  • Virginia
    • McLean, Virginia, United States, 22102
      • Kaiser Mid Atlantic
    • Norfolk, Virginia, United States, 23507
      • Sentara Norfolk General Hospital
  • Washington
    • Seattle, Washington, United States, 98112
      • Swedish Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TAVR; Transcatheter Aortic Valve Replacement (TAVR)	Device: SAPIEN 3 / SAPIEN 3 Ultra / SAPIEN 3 Ultra RESILIA; Patients will be implanted with a SAPIEN 3 / SAPIEN 3 Ultra / SAPIEN 3 Ultra RESILIA heart valve
No Intervention: CS; Clinical Surveillance (CS)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Unplanned cardiovascular hospitalization	The number of patients that had this event	2 years
Left ventricle (LV) mass index	Echocardiographic measurement of the size of the left ventricle	2 years
Stroke volume index	Echocardiographic measurement of the volume of blood pumped out of the left ventricle during contraction.	2 years
Diastolic dysfunction ≥ Grade 2	Echocardiographic measurement of the stiffness of the left ventricle.	2 years
N-Terminal Pro B-type Natriuretic Peptide (NT-ProBNP)	NT-ProBNP is a hormone that measures heart failure. Levels goes up when heart failure develops or gets worse, and levels goes down when heart failure is stable.	2 years
KCCQ overall score	Change from baseline in KCCQ. The KCCQ is a 23-item self-administered questionnaire developed to independently measure the patient's perception of their health status, which includes heart failure symptoms, impact on physical and social function, and how their heart failure impacts their quality of life. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.	2 years
Reduction in LVEF ≥ 5% from baseline AND LVEF < 60%	The number of patients that meet these criteria	2 years
New onset atrial fibrillation	The number of patients that develop this condition	2 years
Death, stroke, or unplanned cardiovascular hospitalization	The number of patients that had this event	2 years
Death, unplanned cardiovascular hospitalization, or decrease of > 10 points in Kansas City Cardiomyopathy Questionnaire (KCCQ)	The number of patients that met all these criteria	2 years

Collaborators and Investigators

• Sponsor: Edwards Lifesciences
• Investigators: Principal Investigator: 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

Study record dates

Study Major Dates

• Study Start (Actual): October 12, 2021
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2037

Study Registration Dates

• First Submitted: May 12, 2021
• First Submitted That Met QC Criteria: May 12, 2021
• First Posted (Actual): May 17, 2021

Study Record Updates

• Last Update Posted (Estimated): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Aortic stenosis; Transcatheter aortic valve replacement (TAVR); SAPIEN 3; SAPIEN 3 Ultra; Moderate aortic stenosis; Transcatheter heart valve; SAPIEN 3 Ultra RESILIA
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Constriction, Pathologic
• Other Study ID Numbers: 2021-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes