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

• Sponsor: Edwards Lifesciences (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03471065
• Collaborator: (none)
• Enrollment: 100
• Locations: 6
• Arm: 1
• Anticipated Duration (Months): 69
• Patients Per Site: 16.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Aortic Valve Stenosis	Device: SAPIEN 3 Ultra Delivery System with the SAPIEN 3 Ultra THV	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 100 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: SAPIEN 3 Ultra SystemSAPIEN 3 Ultra System
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Jun 1, 2018
• Actual Primary Completion Date: Dec 23, 2019
• Anticipated Study Completion Date: Mar 1, 2024

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Procedural Success [Day 0]

   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

Secondary Outcome Measures

1. Major Vascular Complications [Discharge, expected to be within 1-5 days post-procedure]]

   Number of patients with major vascular complications

2. Valve Migration or Embolization [Discharge, expected to be within 1-5 days post-procedure]]

   Number of patients with valve migration or embolization

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

1. New York Heart Association functional class ≥ II

2. Judged by the Heart Team to be at intermediate risk for open surgical therapy

3. 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:

13. Unprotected left main coronary artery

14. SYNTAX score > 32

15. Heart Team assessment that optimal revascularization cannot be performed

16. Iliofemoral vessel characteristics that would preclude safe placement of the introducer sheath

17. Significant abdominal or thoracic aortic disease that would preclude safe passage of the delivery system

18. Active bacterial endocarditis within 180 days of the valve implant procedure

19. Stroke or transient ischemic attack within 90 days of the valve implant procedure

20. Symptomatic carotid or vertebral artery disease or successful treatment of carotid stenosis within 30 days of the valve implant procedure

21. Severe lung disease (Forced Ejection Volume 1 < 50% predicted) or currently on home oxygen

22. Severe pulmonary hypertension

23. Hemodynamic or respiratory instability requiring inotropic support, mechanical ventilation or mechanical heart assistance within 30 days of the valve implant procedure

24. History of cirrhosis or any active liver disease

25. Renal insufficiency and/or renal replacement therapy at the time of screening

26. Leukopenia, anemia, thrombocytopenia, history of bleeding diathesis or coagulopathy or hypercoagulable states

27. Inability to tolerate or condition precluding treatment with antithrombotic therapy during or after the valve implant procedure

28. Absolute contraindications or allergy to iodinated contrast that cannot be adequately treated with pre-medication

29. Significant frailty as determined by the Heart Team

30. Subject refuses blood products

31. Body mass index > 50 kg/m2

32. Estimated life expectancy < 24 months

33. Positive urine or serum pregnancy test in female subjects of childbearing potential

34. Currently participating in an investigational drug or another device study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St. Paul's Hospital	Vancouver	British Columbia	Canada
2	Hamilton Health Sciences	Hamilton	Ontario	Canada
3	Toronto General Hospital	Toronto	Ontario	Canada
4	Institut universitaire de cardiologie et de pneumologie de Québec	Québec City	Quebec	Canada
5	Kings Hospital	London		United Kingdom
6	St. Thomas Hospital	London		United Kingdom

Sponsors and Collaborators

• Edwards Lifesciences

Investigators

• Principal Investigator: John Webb, MD, St. Paul's Hospital
• Principal Investigator: Bernard Prendergast, Prof, St. Thomas Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 1, 2019

More Information

Publications

None provided.

• Responsible Party: Edwards Lifesciences
• ClinicalTrials.gov Identifier: NCT03471065
• Other Study ID Numbers: 2018-03
• First Posted: Mar 20, 2018
• Last Update Posted: Nov 26, 2021
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Keywords provided by Edwards Lifesciences: Transcatheter; Transcatheter Valve Replacement; SAPIEN 3 Ultra
• Additional relevant MeSH terms: Aortic Valve Stenosis; Constriction, Pathologic

Study Results

Participant Flow

Arm/Group Title	Transcatheter Aortic Valve Replacement (TAVR)
Arm/Group Description	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.
Period Title: Overall Study
STARTED	100
COMPLETED	100
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Transcatheter Aortic Valve Replacement (TAVR)
Arm/Group Description	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.
Overall Participants	100
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	83.5 (6.27)
Sex: Female, Male (Count of Participants)
Female	50 50%
Male	50 50%
Race and Ethnicity Not Collected (Count of Participants)
Society of Thoracic Surgeons (STS) Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	3.6 (1.29)
New York Heart Association (NYHA) Class Grouped (Count of Participants)
Class I/II	56 56%
Class III/IV	44 44%

Outcome Measures

1. Primary Outcome

Title	Procedural Success
Description	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
Time Frame	Day 0

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transcatheter Aortic Valve Replacement (TAVR)
Arm/Group Description	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.
Measure Participants	100
Count of Participants [Participants]	100 100%

2. Secondary Outcome

Title	Major Vascular Complications
Description	Number of patients with major vascular complications
Time Frame	Discharge, expected to be within 1-5 days post-procedure]

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transcatheter Aortic Valve Replacement (TAVR)
Arm/Group Description	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.
Measure Participants	100
Count of Participants [Participants]	2 2%

3. Secondary Outcome

Title	Valve Migration or Embolization
Description	Number of patients with valve migration or embolization
Time Frame	Discharge, expected to be within 1-5 days post-procedure]

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transcatheter Aortic Valve Replacement (TAVR)
Arm/Group Description	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.
Measure Participants	100
Count of Participants [Participants]	0 0%

Adverse Events

Time Frame	30-days
Arm/Group Title	Transcatheter Aortic Valve Replacement (TAVR)
Arm/Group Description	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.
All Cause Mortality
	Transcatheter Aortic Valve Replacement (TAVR)
	Affected / at Risk (%)	# Events
Total	1/100 (1%)
Serious Adverse Events
	Transcatheter Aortic Valve Replacement (TAVR)
	Affected / at Risk (%)	# Events
Total	7/100 (7%)
Cardiac disorders
Atrioventricular block complete	7/100 (7%)
Other (Not Including Serious) Adverse Events
	Transcatheter Aortic Valve Replacement (TAVR)
	Affected / at Risk (%)	# Events
Total	24/100 (24%)
Cardiac disorders
Bundle branch block left	11/100 (11%)
Injury, poisoning and procedural complications
Vascular access site haemorrhage	6/100 (6%)
Vascular disorders
Haematoma	7/100 (7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.