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

Primary Purpose

Aortic Valve Stenosis

Status
Active
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
SAPIEN 3 THV
Optimal Heart Failure Therapy
Sponsored by
Cardiovascular Research Foundation, New York
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Aortic Valve Stenosis focused on measuring Valve

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Chandler Regional Medical Center
  • UCSD/Sulpizio Cardiovascular Center
  • University of Southern California - Los Angeles
  • UCLA Medical Center
  • St. Joseph Hospital
  • UCSF
  • Medical Center of the Rockies
  • Yale University
  • Medstar Washington Hospital Center
  • University of Miami
  • Cleveland Clinic Florida
  • Advocate Christ Hospital
  • Northwestern University
  • Alexian Brothers Medical Center
  • Evanston Hospital/NorthShore Univ. Health System
  • Advocate Lutheran General Hospital
  • Carle Foundation Hospital
  • Maine Medical Center
  • Tufts Medical Center
  • Massachusetts General Hospital
  • Beaumont Hospital
  • Ascension St. Mary's Hospital
  • Minneapolis Heart Institute
  • Mayo Clinic - Rochester
  • HealthEast Medical Research Institute
  • Washington University in St. Louis
  • University of Nebraska Medical Center
  • Morristown Memorial
  • NYU Langone Medical Center
  • Columbia University Medical Center/New York Presbyterian Hospital
  • St. Francis Hospital
  • Oregon Health Science University (OHSU)
  • University of Pennsylvania
  • UPMC Presbyterian
  • PinnacleHealth Cardiovascular Institute
  • WellSpan York Hospital
  • Rhode Island Hospital
  • Vanderbilt Heart and Vascular
  • Seton Medical Center Austin
  • IHC Health Services, Inc. dba Intermountain Medical Center
  • University of Vermont Medical Center
  • Virginia Commonwealth University (VCU)
  • Swedish Medical Center
  • Oklahoma Heart Hospital
  • Advocate Aurora- St. Lukes
  • Medical College of Wisconsin
  • St. Michael's Hospital
  • University Medical Center Utrecht
  • Leiden University Medical Center
  • Erasmus Medical Center
  • Isala Clinics

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

TAVR (with SAPIEN 3 THV) and OHFT

OHFT

Arm Description

Transcatheter heart valve and Optimal Heart Failure Therapy

Optimal Heart Failure Therapy

Outcomes

Primary Outcome Measures

All-Cause Death
Hierarchical occurrence within efficacy assessment time interval (EATI) of:
Disabling Stroke
Hierarchical occurrence within efficacy assessment time interval (EATI) of:
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:
Change in KCCQ relative to baseline
Hierarchical occurrence within efficacy assessment time interval (EATI) of:

Secondary Outcome Measures

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)
-All-cause death within EATI
-All-cause death within EATI

Full Information

First Posted
January 15, 2016
Last Updated
July 14, 2023
Sponsor
Cardiovascular Research Foundation, New York
Collaborators
Cardialysis BV, Avania
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1. Study Identification

Unique Protocol Identification Number
NCT02661451
Brief Title
Transcatheter Aortic Valve Replacement to UNload the Left Ventricle in Patients With ADvanced Heart Failure (TAVR UNLOAD)
Official Title
Transcatheter Aortic Valve Replacement to UNload the Left Ventricle in Patients With ADvanced Heart Failure: A Randomized Trial (TAVR UNLOAD)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 2016 (Actual)
Primary Completion Date
February 28, 2023 (Actual)
Study Completion Date
February 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cardiovascular Research Foundation, New York
Collaborators
Cardialysis BV, Avania

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Aortic Valve Stenosis
Keywords
Valve

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
178 (Actual)

8. Arms, Groups, and Interventions

Arm Title
TAVR (with SAPIEN 3 THV) and OHFT
Arm Type
Experimental
Arm Description
Transcatheter heart valve and Optimal Heart Failure Therapy
Arm Title
OHFT
Arm Type
Active Comparator
Arm Description
Optimal Heart Failure Therapy
Intervention Type
Device
Intervention Name(s)
SAPIEN 3 THV
Intervention Type
Biological
Intervention Name(s)
Optimal Heart Failure Therapy
Primary Outcome Measure Information:
Title
All-Cause Death
Description
Hierarchical occurrence within efficacy assessment time interval (EATI) of:
Time Frame
12 months
Title
Disabling Stroke
Description
Hierarchical occurrence within efficacy assessment time interval (EATI) of:
Time Frame
12 months
Title
Hospitalizations related to heart failure, symptomatic aortic valve disease or non-disabling stroke -or - Clinically significant worsening of heart failure (heart failure hospitalization equivalent).
Description
Hierarchical occurrence within efficacy assessment time interval (EATI) of:
Time Frame
12 months
Title
Change in KCCQ relative to baseline
Description
Hierarchical occurrence within efficacy assessment time interval (EATI) of:
Time Frame
12 months
Secondary Outcome Measure Information:
Title
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:
Description
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)
Time Frame
12 month
Title
-All-cause death within EATI
Description
-All-cause death within EATI
Time Frame
12 month

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria All candidates for this study must meet all of the following inclusion criteria: Age ≥18 years Heart Failure with NYHA class ≥ 2 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. 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. Left ventricular (LV) ejection fraction (EF) < 50% at rest Anatomically suitable for transfemoral TAVR with the SAPIEN 3 or SAPIEN 3 Ultra THV 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: LVEF < 20% or persistent need for intravenous inotropic support Hospitalization for acute decompensated HF within 2 weeks prior to randomization Cardiac resynchronization therapy (CRT) device implantation within 1 month prior to randomization Coronary artery revascularization (PCI or CABG) within 1 month prior to randomization In need and suitable for revascularization per heart team consensus Severe aortic and/or mitral regurgitation Congenital unicuspid or congenital bicuspid aortic valve Concomitant non-aortic valvular disease with a formal indication for valve surgery per established guidelines (ESC/ACC/AHA) Previous aortic valve replacement (mechanical or bioprosthetic) Severe RV dysfunction Previous stroke with permanent disability (modified Rankin score ≥ 2) Severe lung disease as indicated by FEV1 <30% predicted or need for chronic daytime supplemental oxygen therapy Severe chronic kidney disease: glomerular filtration rate (GFR) < 30 mL/min by MDRD or need for renal replacement therapy Gastrointestinal (GI) bleeding within the past 3 months Liver cirrhosis Child-Pugh C Active systemic infection, including active endocarditis Unwilling to accept blood transfusion Evidence of intracardiac mass, thrombus or vegetation Absence of minimum amount of aortic valve calcification necessary for TAVR with the SAPIEN 3 or SAPIEN 3 Ultra THV Hypersensitivity or contraindication to clopidogrel, aspirin, or to oral anticoagulation if indicated (e.g. subject in atrial fibrillation) Sensitivity to contrast media which cannot be adequately pre-medicated Women of child-bearing potential Clinical signs of dementia Other medical, social, or psychological conditions that precludes appropriate consent and follow-up Life expectancy < 2 years due to cancer or other non-cardiac chronic diseases Unwillingness to undergo follow-up investigations Currently participating in an investigational drug or another device trial that has not reached its primary endpoint (excluding registries)
Facility Information:
Facility Name
Chandler Regional Medical Center
City
Chandler
State/Province
Arizona
ZIP/Postal Code
85224
Country
United States
Facility Name
UCSD/Sulpizio Cardiovascular Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
University of Southern California - Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
St. Joseph Hospital
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
UCSF
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Medical Center of the Rockies
City
Loveland
State/Province
Colorado
ZIP/Postal Code
80538
Country
United States
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
Medstar Washington Hospital Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Cleveland Clinic Florida
City
Weston
State/Province
Florida
ZIP/Postal Code
33331
Country
United States
Facility Name
Advocate Christ Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60453
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Alexian Brothers Medical Center
City
Elk Grove Village
State/Province
Illinois
ZIP/Postal Code
60007
Country
United States
Facility Name
Evanston Hospital/NorthShore Univ. Health System
City
Evanston
State/Province
Illinois
ZIP/Postal Code
60210
Country
United States
Facility Name
Advocate Lutheran General Hospital
City
Park Ridge
State/Province
Illinois
ZIP/Postal Code
60068
Country
United States
Facility Name
Carle Foundation Hospital
City
Urbana
State/Province
Illinois
ZIP/Postal Code
61801
Country
United States
Facility Name
Maine Medical Center
City
Portland
State/Province
Maine
ZIP/Postal Code
04102
Country
United States
Facility Name
Tufts Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Beaumont Hospital
City
Royal Oak
State/Province
Michigan
ZIP/Postal Code
48072
Country
United States
Facility Name
Ascension St. Mary's Hospital
City
Saginaw
State/Province
Michigan
ZIP/Postal Code
48601
Country
United States
Facility Name
Minneapolis Heart Institute
City
Minneapolis
State/Province
Minnesota
Country
United States
Facility Name
Mayo Clinic - Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
HealthEast Medical Research Institute
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55102
Country
United States
Facility Name
Washington University in St. Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
Morristown Memorial
City
Morristown
State/Province
New Jersey
ZIP/Postal Code
07962
Country
United States
Facility Name
NYU Langone Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Columbia University Medical Center/New York Presbyterian Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
St. Francis Hospital
City
Roslyn
State/Province
New York
ZIP/Postal Code
11576
Country
United States
Facility Name
Oregon Health Science University (OHSU)
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
UPMC Presbyterian
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
PinnacleHealth Cardiovascular Institute
City
Wormleysburg
State/Province
Pennsylvania
ZIP/Postal Code
17043
Country
United States
Facility Name
WellSpan York Hospital
City
York
State/Province
Pennsylvania
ZIP/Postal Code
17405
Country
United States
Facility Name
Rhode Island Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02904
Country
United States
Facility Name
Vanderbilt Heart and Vascular
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Seton Medical Center Austin
City
Austin
State/Province
Texas
ZIP/Postal Code
78705
Country
United States
Facility Name
IHC Health Services, Inc. dba Intermountain Medical Center
City
Murray
State/Province
Utah
ZIP/Postal Code
84107
Country
United States
Facility Name
University of Vermont Medical Center
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05401
Country
United States
Facility Name
Virginia Commonwealth University (VCU)
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
Swedish Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98125
Country
United States
Facility Name
Oklahoma Heart Hospital
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53211
Country
United States
Facility Name
Advocate Aurora- St. Lukes
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53215
Country
United States
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
St. Michael's Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5B 1W8
Country
Canada
Facility Name
University Medical Center Utrecht
City
Utrecht
State/Province
TH
ZIP/Postal Code
3584CX
Country
Netherlands
Facility Name
Leiden University Medical Center
City
Leiden
Country
Netherlands
Facility Name
Erasmus Medical Center
City
Rotterdam
Country
Netherlands
Facility Name
Isala Clinics
City
Zwolle
Country
Netherlands

12. IPD Sharing Statement

Citations:
PubMed Identifier
30704832
Citation
Esquitin KA, Khalique OK, Liu Q, Kodali SK, Marcoff L, Nazif TM, George I, Vahl TP, Leon MB, Hahn RT. Accuracy of the Single Cycle Length Method for Calculation of Aortic Effective Orifice Area in Irregular Heart Rhythms. J Am Soc Echocardiogr. 2019 Mar;32(3):344-350. doi: 10.1016/j.echo.2018.11.018. Epub 2019 Jan 28.
Results Reference
derived

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

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