Transcatheter Aortic Valve Replacement to UNload the Left Ventricle in Patients With ADvanced Heart Failure (TAVR UNLOAD)

Aortic Valve Stenosis Clinical Trial

Official title:

Transcatheter Aortic Valve Replacement to UNload the Left Ventricle in Patients With ADvanced Heart Failure: A Randomized Trial (TAVR UNLOAD)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02661451
• Other study ID #: TAVR Unload
• Status: Active, not recruiting
• Phase: N/A
• Start date: September 2016
• Est. completion date: February 2025

Study information

• Verified date: July 2023
• Source: Cardiovascular Research Foundation, New York
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this study is to determine the safety and efficacy of transcatheter aortic valve replacement (TAVR) via a transfemoral approach in HF patients with moderate AS as compared with OHFT.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 178
• Est. completion date: February 2025
• Est. primary completion date: February 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

All candidates for this study must meet all of the following inclusion criteria:

1. Age =18 years

2. Heart Failure with NYHA class = 2

3. Under appropriate and stable guideline-directed HF therapy for a minimum of 1 month prior to randomization.

Note: Patients are expected to be on appropriate pharmacologic therapy and if indicated CRT for heart failure. (12, 13) Patients with aortic stenosis may not be able to tolerate maximal doses of heart failure medications and no specific guidelines exist for the medical treatment of heart failure in the setting of aortic stenosis. It is expected that the heart failure PI will review the medical therapy and confirm that it is appropriate for the patient's condition.

4. Moderate AS confirmed by the echo core lab. Moderate AS is defined as an aortic valve area (AVA) >1.0 cm2 and =1.5 cm2 on rest echo or if =1.0 cm2 at rest and low-flow AS is suspected when the an AVA > 1.0 cm2 with low dose dobutamine stress echo (DSE). Patients with AVA<1.0 cm2 but with an indexed AVA of >0.6 cm2/m2 on either rest or DSE are also eligible. Similarly, patients with AVA >1.5 cm2 but with indexed AVA<0.9 cm2/m2 on either rest of DSE are also eligible.

Note: Typically such cases will demonstrate,

• Mean trans-aortic gradient (MG) = 20 mmHg and < 40 mmHg at rest and aortic valve area (AVA) > 1.0 cm2 and =1.5 cm2 (or AVA < 1.0 cm2 but indexed AVA > 0.6 cm2) at rest

OR

• Mean trans-aortic gradient (MG) = 20 mmHg and < 40 mmHg and aortic valve area (AVA) =1.0 cm2 at rest AND MG < 40 mmHg and aortic valve area (AVA)

•>1.0 cm2 (or AVA < 1.0 cm2 but indexed AVA > 0.6 cm2) with low dose dobutamine stress echo (DSE).

In atypical cases (for example mean gradient is below 20 mmHg but valve area is consistent with moderate AS, the final eligibility determination in regards to diagnosis of moderate AS will be made by the echocardiographic core lab.

5. Left ventricular (LV) ejection fraction (EF) < 50% at rest

6. Anatomically suitable for transfemoral TAVR with the SAPIEN 3 or SAPIEN 3 Ultra THV

7. Able to provide independent informed consent (i.e., not requiring a legally authorized representative)

Exclusion Criteria

Candidates are excluded from the study if any of the following conditions are present:

1. LVEF < 20% or persistent need for intravenous inotropic support

2. Hospitalization for acute decompensated HF within 2 weeks prior to randomization

3. Cardiac resynchronization therapy (CRT) device implantation within 1 month prior to randomization

4. Coronary artery revascularization (PCI or CABG) within 1 month prior to randomization

5. In need and suitable for revascularization per heart team consensus

6. Severe aortic and/or mitral regurgitation

7. Congenital unicuspid or congenital bicuspid aortic valve

8. Concomitant non-aortic valvular disease with a formal indication for valve surgery per established guidelines (ESC/ACC/AHA)

9. Previous aortic valve replacement (mechanical or bioprosthetic)

10. Severe RV dysfunction

11. Previous stroke with permanent disability (modified Rankin score = 2)

12. Severe lung disease as indicated by FEV1 <30% predicted or need for chronic daytime supplemental oxygen therapy

13. Severe chronic kidney disease: glomerular filtration rate (GFR) < 30 mL/min by MDRD or need for renal replacement therapy

14. Gastrointestinal (GI) bleeding within the past 3 months

15. Liver cirrhosis Child-Pugh C

16. Active systemic infection, including active endocarditis

17. Unwilling to accept blood transfusion

18. Evidence of intracardiac mass, thrombus or vegetation

19. Absence of minimum amount of aortic valve calcification necessary for TAVR with the SAPIEN 3 or SAPIEN 3 Ultra THV

20. Hypersensitivity or contraindication to clopidogrel, aspirin, or to oral anticoagulation if indicated (e.g. subject in atrial fibrillation)

21. Sensitivity to contrast media which cannot be adequately pre-medicated

22. Women of child-bearing potential

23. Clinical signs of dementia

24. Other medical, social, or psychological conditions that precludes appropriate consent and follow-up

25. Life expectancy < 2 years due to cancer or other non-cardiac chronic diseases

26. Unwillingness to undergo follow-up investigations

27. Currently participating in an investigational drug or another device trial that has not reached its primary endpoint (excluding registries)

Related Conditions & MeSH terms

• Aortic Valve Stenosis
• Heart Failure

Intervention

Device:
• SAPIEN 3 THV

Biological:
• Optimal Heart Failure Therapy

Locations

Country	Name	City	State
Canada	St. Michael's Hospital	Toronto	Ontario
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Erasmus Medical Center	Rotterdam
Netherlands	University Medical Center Utrecht	Utrecht	TH
Netherlands	Isala Clinics	Zwolle
United States	Seton Medical Center Austin	Austin	Texas
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	University of Vermont Medical Center	Burlington	Vermont
United States	Chandler Regional Medical Center	Chandler	Arizona
United States	Advocate Christ Hospital	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
United States	Alexian Brothers Medical Center	Elk Grove Village	Illinois
United States	Evanston Hospital/NorthShore Univ. Health System	Evanston	Illinois
United States	UCSD/Sulpizio Cardiovascular Center	La Jolla	California
United States	UCLA Medical Center	Los Angeles	California
United States	University of Southern California - Los Angeles	Los Angeles	California
United States	Medical Center of the Rockies	Loveland	Colorado
United States	University of Miami	Miami	Florida
United States	Advocate Aurora- St. Lukes	Milwaukee	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Oklahoma Heart Hospital	Milwaukee	Wisconsin
United States	Minneapolis Heart Institute	Minneapolis	Minnesota
United States	Morristown Memorial	Morristown	New Jersey
United States	IHC Health Services, Inc. dba Intermountain Medical Center	Murray	Utah
United States	Vanderbilt Heart and Vascular	Nashville	Tennessee
United States	Yale University	New Haven	Connecticut
United States	Columbia University Medical Center/New York Presbyterian Hospital	New York	New York
United States	NYU Langone Medical Center	New York	New York
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	St. Joseph Hospital	Orange	California
United States	Advocate Lutheran General Hospital	Park Ridge	Illinois
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	UPMC Presbyterian	Pittsburgh	Pennsylvania
United States	Maine Medical Center	Portland	Maine
United States	Oregon Health Science University (OHSU)	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Virginia Commonwealth University (VCU)	Richmond	Virginia
United States	Mayo Clinic - Rochester	Rochester	Minnesota
United States	St. Francis Hospital	Roslyn	New York
United States	Beaumont Hospital	Royal Oak	Michigan
United States	Ascension St. Mary's Hospital	Saginaw	Michigan
United States	Washington University in St. Louis	Saint Louis	Missouri
United States	HealthEast Medical Research Institute	Saint Paul	Minnesota
United States	UCSF	San Francisco	California
United States	Swedish Medical Center	Seattle	Washington
United States	Carle Foundation Hospital	Urbana	Illinois
United States	Medstar Washington Hospital Center	Washington	District of Columbia
United States	Cleveland Clinic Florida	Weston	Florida
United States	PinnacleHealth Cardiovascular Institute	Wormleysburg	Pennsylvania
United States	WellSpan York Hospital	York	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Cardiovascular Research Foundation, New York	Avania, Cardialysis BV

Countries where clinical trial is conducted

United States,  Canada,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All-Cause Death	Hierarchical occurrence within efficacy assessment time interval (EATI) of:	12 months
Primary	Disabling Stroke	Hierarchical occurrence within efficacy assessment time interval (EATI) of:	12 months
Primary	Hospitalizations related to heart failure, symptomatic aortic valve disease or non-disabling stroke -or - Clinically significant worsening of heart failure (heart failure hospitalization equivalent).	Hierarchical occurrence within efficacy assessment time interval (EATI) of:	12 months
Primary	Change in KCCQ relative to baseline	Hierarchical occurrence within efficacy assessment time interval (EATI) of:	12 months
Secondary	MACCE defined as the composite of all-cause death, all stroke, and hospitalizations for heart failure or symptomatic aortic valve disease or clinically significant worsening of heart failure within EATI. Hierarchical occurrence within EATI of:	All-cause death; Disabling stroke; Hospitalizations related to heart failure, symptomatic aortic valve disease or non-disabling stroke or clinically significant worsening of heart failure (heart failure event)	12 month
Secondary	-All-cause death within EATI	-All-cause death within EATI	12 month