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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Aortic Valve Stenosis
• Intervention / Treatment: Device: SAPIEN 3 THV; Biological: Optimal Heart Failure Therapy

• Study Type: Interventional
• Enrollment (Actual): 178
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
• Netherlands
  • Leiden, Netherlands
    • Leiden University Medical Center
  • Rotterdam, Netherlands
    • Erasmus Medical Center
  • Zwolle, Netherlands
    • Isala Clinics
  • TH
    • Utrecht, TH, Netherlands, 3584CX
      • University Medical Center Utrecht
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Chandler Regional Medical Center
  • California
    • La Jolla, California, United States, 92037
      • UCSD/Sulpizio Cardiovascular Center
    • Los Angeles, California, United States, 90095
      • UCLA Medical Center
    • Los Angeles, California, United States, 90033
      • University of Southern California - Los Angeles
    • Orange, California, United States, 92868
      • St. Joseph Hospital
    • San Francisco, California, United States, 94143
      • UCSF
  • Colorado
    • Loveland, Colorado, United States, 80538
      • Medical Center of the Rockies
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • MedStar Washington Hospital Center
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
    • Weston, Florida, United States, 33331
      • Cleveland Clinic Florida
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60453
      • Advocate Christ Hospital
    • Elk Grove Village, Illinois, United States, 60007
      • Alexian Brothers Medical Center
    • Evanston, Illinois, United States, 60210
      • Evanston Hospital/NorthShore Univ. Health System
    • Park Ridge, Illinois, United States, 60068
      • Advocate Lutheran General Hospital
    • Urbana, Illinois, United States, 61801
      • Carle Foundation Hospital
  • Maine
    • Portland, Maine, United States, 04102
      • Maine Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Michigan
    • Royal Oak, Michigan, United States, 48072
      • Beaumont Hospital
    • Saginaw, Michigan, United States, 48601
      • Ascension St. Mary's Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States
      • Minneapolis Heart Institute
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic - Rochester
    • Saint Paul, Minnesota, United States, 55102
      • HealthEast Medical Research Institute
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University in St. Louis
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New Jersey
    • Morristown, New Jersey, United States, 07962
      • Morristown Memorial
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Medical Center
    • New York, New York, United States, 10032
      • Columbia University Medical Center/New York Presbyterian Hospital
    • Roslyn, New York, United States, 11576
      • St. Francis Hospital
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health Science University (OHSU)
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Presbyterian
    • Wormleysburg, Pennsylvania, United States, 17043
      • PinnacleHealth Cardiovascular Institute
    • York, Pennsylvania, United States, 17405
      • WellSpan York Hospital
  • Rhode Island
    • Providence, Rhode Island, United States, 02904
      • Rhode Island Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Vanderbilt Heart and Vascular
  • Texas
    • Austin, Texas, United States, 78705
      • Seton Medical Center Austin
  • Utah
    • Murray, Utah, United States, 84107
      • IHC Health Services, Inc. dba Intermountain Medical Center
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont Medical Center
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University (VCU)
  • Washington
    • Seattle, Washington, United States, 98125
      • Swedish Medical Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin
    • Milwaukee, Wisconsin, United States, 53211
      • Oklahoma Heart Hospital
    • Milwaukee, Wisconsin, United States, 53215
      • Advocate Aurora- St. Lukes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

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 (with SAPIEN 3 THV) and OHFT; Transcatheter heart valve and Optimal Heart Failure Therapy	Device: SAPIEN 3 THV; Biological: Optimal Heart Failure Therapy
Active Comparator: OHFT; Optimal Heart Failure Therapy	Biological: Optimal Heart Failure Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-Cause Death	Hierarchical occurrence within efficacy assessment time interval (EATI) of:	12 months
Disabling Stroke	Hierarchical occurrence within efficacy assessment time interval (EATI) of:	12 months
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
Change in KCCQ relative to baseline	Hierarchical occurrence within efficacy assessment time interval (EATI) of:	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
-All-cause death within EATI	-All-cause death within EATI	12 month

Collaborators and Investigators

• Sponsor: Cardiovascular Research Foundation, New York
• Collaborators: Cardialysis BV; Avania

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2016
• Primary Completion (Actual): February 28, 2023
• Study Completion (Estimated): February 1, 2025

Study Registration Dates

• First Submitted: January 15, 2016
• First Submitted That Met QC Criteria: January 21, 2016
• First Posted (Estimated): January 22, 2016

Study Record Updates

• Last Update Posted (Actual): July 18, 2023
• Last Update Submitted That Met QC Criteria: July 14, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Valve
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Heart Failure; Aortic Valve Stenosis
• Other Study ID Numbers: TAVR Unload