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

NCT02661451 | Active Not Recruiting DMC

• 1 other identifier: TAVR Unload
• Study Type: interventional
• Target: 178
• Locations: 3 countries
• Sites: 51

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.

Conditions

Aortic Valve Stenosis

Keywords

Valve

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (2)

• 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:

  12 month

• -All-cause death within EATI

  12 month

Study Arms (2)

TAVR (with SAPIEN 3 THV) and OHFT

EXPERIMENTAL

Transcatheter heart valve and Optimal Heart Failure Therapy

Device: SAPIEN 3 THV; Biological: Optimal Heart Failure Therapy

OHFT

ACTIVE COMPARATOR

Optimal Heart Failure Therapy

Biological: Optimal Heart Failure Therapy

Interventions

SAPIEN 3 THV DEVICE

TAVR (with SAPIEN 3 THV) and OHFT

Optimal Heart Failure Therapy BIOLOGICAL

OHFT; TAVR (with SAPIEN 3 THV) and OHFT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Cardiovascular Research Foundation, New York: lead
• Cardialysis BV: collaborator
• Avania: collaborator

Study Sites (51)

Chandler Regional Medical Center

Chandler, Arizona, 85224, United States

Location

UCSD/Sulpizio Cardiovascular Center

La Jolla, California, 92037, United States

Location

University of Southern California - Los Angeles

Los Angeles, California, 90033, United States

Location

UCLA Medical Center

Los Angeles, California, 90095, United States

Location

St. Joseph Hospital

Orange, California, 92868, United States

Location

UCSF

San Francisco, California, 94143, United States

Location

Medical Center of the Rockies

Loveland, Colorado, 80538, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Medstar Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Cleveland Clinic Florida

Weston, Florida, 33331, United States

Location

Advocate Christ Hospital

Chicago, Illinois, 60453, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Alexian Brothers Medical Center

Elk Grove Village, Illinois, 60007, United States

Location

Evanston Hospital/NorthShore Univ. Health System

Evanston, Illinois, 60210, United States

Location

Advocate Lutheran General Hospital

Park Ridge, Illinois, 60068, United States

Location

Carle Foundation Hospital

Urbana, Illinois, 61801, United States

Location

Maine Medical Center

Portland, Maine, 04102, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beaumont Hospital

Royal Oak, Michigan, 48072, United States

Location

Ascension St. Mary's Hospital

Saginaw, Michigan, 48601, United States

Location

Minneapolis Heart Institute

Minneapolis, Minnesota, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

HealthEast Medical Research Institute

Saint Paul, Minnesota, 55102, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Morristown Memorial

Morristown, New Jersey, 07962, United States

Location

NYU Langone Medical Center

New York, New York, 10016, United States

Location

Columbia University Medical Center/New York Presbyterian Hospital

New York, New York, 10032, United States

Location

St. Francis Hospital

Roslyn, New York, 11576, United States

Location

Oregon Health Science University (OHSU)

Portland, Oregon, 97239, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

UPMC Presbyterian

Pittsburgh, Pennsylvania, 15213, United States

Location

PinnacleHealth Cardiovascular Institute

Wormleysburg, Pennsylvania, 17043, United States

Location

WellSpan York Hospital

York, Pennsylvania, 17405, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02904, United States

Location

Vanderbilt Heart and Vascular

Nashville, Tennessee, 37203, United States

Location

Seton Medical Center Austin

Austin, Texas, 78705, United States

Location

IHC Health Services, Inc. dba Intermountain Medical Center

Murray, Utah, 84107, United States

Location

University of Vermont Medical Center

Burlington, Vermont, 05401, United States

Location

Virginia Commonwealth University (VCU)

Richmond, Virginia, 23298, United States

Location

Swedish Medical Center

Seattle, Washington, 98125, United States

Location

Oklahoma Heart Hospital

Milwaukee, Wisconsin, 53211, United States

Location

Advocate Aurora- St. Lukes

Milwaukee, Wisconsin, 53215, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

University Medical Center Utrecht

Utrecht, TH, 3584CX, Netherlands

Location

Leiden University Medical Center

Leiden, Netherlands

Location

Erasmus Medical Center

Rotterdam, Netherlands

Location

Isala Clinics

Zwolle, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 30704832 DERIVED

MeSH Terms

Conditions

Aortic Valve Stenosis

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2016
• First Posted: January 22, 2016
• Study Start: September 1, 2016
• Primary Completion: February 28, 2023
• Study Completion: February 1, 2025
• Last Updated: November 27, 2024

Record last verified: 2024-11

Locations

CA (1); NL (4); US (46)