Clinical trial NCT02661451: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Aortic Valve Stenosis
Keywords: Valve
Lead sponsor: Cardiovascular Research Foundation, New York
Sponsor class: OTHER
Collaborators: name: Cardialysis BV
name: Avania
First posted: 2016-01-22
Enrollment: 178
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: All-Cause Death
timeFrame: 12 months
measure: Disabling Stroke
timeFrame: 12 months
measure: Hospitalizations related to heart failure, symptomatic aortic valve disease or non-disabling stroke -or - Clinically significant worsening of heart failure (heart failure hospitalization equivalent).
timeFrame: 12 months
measure: Change in KCCQ relative to baseline
timeFrame: 12 months
Secondary outcomes:
measure: 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:
timeFrame: 12 month
measure: -All-cause death within EATI
timeFrame: 12 month
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Chandler Regional Medical Center
state: Arizona
city: La Jolla
country: United States
facility: UCSD/Sulpizio Cardiovascular Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California - Los Angeles
state: California
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Orange
country: United States
facility: St. Joseph Hospital
state: California
city: San Francisco
country: United States
facility: UCSF
state: California
city: Loveland
country: United States
facility: Medical Center of the Rockies
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Washington
country: United States
facility: Medstar Washington Hospital Center
state: District of Columbia
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Chicago
country: United States
facility: Advocate Christ Hospital
state: Illinois
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Elk Grove Village
country: United States
facility: Alexian Brothers Medical Center
state: Illinois
city: Evanston
country: United States
facility: Evanston Hospital/NorthShore Univ. Health System
state: Illinois
city: Park Ridge
country: United States
facility: Advocate Lutheran General Hospital
state: Illinois
city: Urbana
country: United States
facility: Carle Foundation Hospital
state: Illinois
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Royal Oak
country: United States
facility: Beaumont Hospital
state: Michigan
city: Saginaw
country: United States
facility: Ascension St. Mary's Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Saint Paul
country: United States
facility: HealthEast Medical Research Institute
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Morristown
country: United States
facility: Morristown Memorial
state: New Jersey
city: New York
country: United States
facility: NYU Langone Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center/New York Presbyterian Hospital
state: New York
city: Roslyn
country: United States
facility: St. Francis Hospital
state: New York
city: Portland
country: United States
facility: Oregon Health Science University (OHSU)
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Presbyterian
state: Pennsylvania
city: Wormleysburg
country: United States
facility: PinnacleHealth Cardiovascular Institute
state: Pennsylvania
city: York
country: United States
facility: WellSpan York Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Nashville
country: United States
facility: Vanderbilt Heart and Vascular
state: Tennessee
city: Austin
country: United States
facility: Seton Medical Center Austin
state: Texas
city: Murray
country: United States
facility: IHC Health Services, Inc. dba Intermountain Medical Center
state: Utah
city: Burlington
country: United States
facility: University of Vermont Medical Center
state: Vermont
city: Richmond
country: United States
facility: Virginia Commonwealth University (VCU)
state: Virginia
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Oklahoma Heart Hospital
state: Wisconsin
city: Milwaukee
country: United States
facility: Advocate Aurora- St. Lukes
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
state: TH
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: Zwolle
country: Netherlands
facility: Isala Clinics
Study officials:
References:
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.