The SAPIEN 3 Ultra System in Intermediate Risk Patients With Symptomatic, Severe Aortic Stenosis

A Prospective, Single-arm, Multicenter Study of the SAPIEN 3 Ultra System in Intermediate Risk Patients With Severe, Calcific, Aortic Stenosis Requiring Aortic Valve Replacement

This study will confirm the procedural safety and performance of the SAPIEN 3 Ultra System in subjects with severe, calcific AS who are at intermediate operative risk for standard aortic valve replacement.

Study Overview

• Status: Active, not recruiting
• Conditions: Aortic Valve Stenosis
• Intervention / Treatment: Device: SAPIEN 3 Ultra Delivery System with the SAPIEN 3 Ultra THV

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada
      • St. Paul's Hospital
  • Ontario
    • Hamilton, Ontario, Canada
      • Hamilton Health Sciences
    • Toronto, Ontario, Canada
      • Toronto General Hospital
  • Quebec
    • Québec City, Quebec, Canada
      • Institut Universitaire de Cardiologie et de Pneumologie de Quebec
• United Kingdom
  • London, United Kingdom
    • St. Thomas Hospital
  • London, United Kingdom
    • Kings Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Severe, calcific aortic stenosis meeting the following transthoracic echocardiogram criteria:

   • Aortic valve area ≤ 1.0 cm2 OR aortic valve area index ≤ 0.6 cm2/m2
   • Jet velocity ≥ 4.0 m/s OR mean gradient ≥ 40 mmHg
2. New York Heart Association functional class ≥ II
3. Judged by the Heart Team to be at intermediate risk for open surgical therapy
4. The subject has been informed of the nature of the study, agrees to its provisions and has provided written informed consent.

Exclusion Criteria:

1. Native aortic annulus size unsuitable for available THV sizes on 3D imaging analysis
2. Aortic valve is unicuspid, bicuspid or non-calcified
3. Pre-existing mechanical or bioprosthetic valve in any position.
4. Severe aortic regurgitation (> 3+)
5. Severe mitral regurgitation (> 3+) or ≥ moderate stenosis
6. Ventricular dysfunction with left ventricular ejection fraction < 30%
7. Cardiac imaging evidence of intracardiac mass, thrombus or vegetation
8. Evidence of an acute myocardial infarction ≤ 30 days before the valve implant procedure
9. Subjects with planned concomitant ablation for atrial fibrillation
10. Hypertrophic cardiomyopathy with obstruction
11. Coronary anatomy that increases the risk of coronary artery obstruction post-TAVR

12. Complex coronary artery disease:

    1. Unprotected left main coronary artery
    2. SYNTAX score > 32
    3. Heart Team assessment that optimal revascularization cannot be performed
13. Iliofemoral vessel characteristics that would preclude safe placement of the introducer sheath
14. Significant abdominal or thoracic aortic disease that would preclude safe passage of the delivery system
15. Active bacterial endocarditis within 180 days of the valve implant procedure
16. Stroke or transient ischemic attack within 90 days of the valve implant procedure
17. Symptomatic carotid or vertebral artery disease or successful treatment of carotid stenosis within 30 days of the valve implant procedure
18. Severe lung disease (Forced Ejection Volume 1 < 50% predicted) or currently on home oxygen
19. Severe pulmonary hypertension
20. Hemodynamic or respiratory instability requiring inotropic support, mechanical ventilation or mechanical heart assistance within 30 days of the valve implant procedure
21. History of cirrhosis or any active liver disease
22. Renal insufficiency and/or renal replacement therapy at the time of screening
23. Leukopenia, anemia, thrombocytopenia, history of bleeding diathesis or coagulopathy or hypercoagulable states
24. Inability to tolerate or condition precluding treatment with antithrombotic therapy during or after the valve implant procedure
25. Absolute contraindications or allergy to iodinated contrast that cannot be adequately treated with pre-medication
26. Significant frailty as determined by the Heart Team
27. Subject refuses blood products
28. Body mass index > 50 kg/m2
29. Estimated life expectancy < 24 months
30. Positive urine or serum pregnancy test in female subjects of childbearing potential
31. Currently participating in an investigational drug or another device study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Transcatheter Aortic Valve Replacement (TAVR)	Device: SAPIEN 3 Ultra Delivery System with the SAPIEN 3 Ultra THV; Patients will be implanted with the SAPIEN 3 Ultra THV (20, 23 and 26 mm) or SAPIEN 3 THV (29 mm) using the SAPIEN 3 Ultra Delivery System.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Procedural Success	The number of patients with procedural success, defined as freedom from all of the following at exit from the procedure room: Mortality; Conversion to surgery; Moderate or severe paravalvular regurgitation	Day 0

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Vascular Complications	Number of patients with major vascular complications	Discharge, expected to be within 1-5 days post-procedure]
Valve Migration or Embolization	Number of patients with valve migration or embolization	Discharge, expected to be within 1-5 days post-procedure]

Collaborators and Investigators

• Sponsor: Edwards Lifesciences
• Investigators: Principal Investigator: Bernard Prendergast, Prof, St. Thomas Hospital; Principal Investigator: John Webb, MD, St. Paul's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2018
• Primary Completion (Actual): December 23, 2019
• Study Completion (Estimated): February 1, 2025

Study Registration Dates

• First Submitted: March 5, 2018
• First Submitted That Met QC Criteria: March 13, 2018
• First Posted (Actual): March 20, 2018

Study Record Updates

• Last Update Posted (Actual): November 30, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Transcatheter; SAPIEN 3 Ultra; Transcatheter Valve Replacement
• 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: 2018-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be available to other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes