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)
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.
Study Type
Interventional
Primary Outcome
All-Cause Death
Secondary Outcome
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:
Condition
Aortic Valve Stenosis
Intervention
SAPIEN 3 THV
Study Arms / Comparison Groups
TAVR (with SAPIEN 3 THV) and OHFT
Description: Transcatheter heart valve and Optimal Heart Failure Therapy
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Device
Estimated Enrollment
300
Start Date
September 2016
Completion Date
March 2022
Primary Completion Date
December 2021
Eligibility Criteria
Inclusion Criteria
All candidates for this study must meet all of the following inclusion criteria:
1. Age ≥18 years
2. NYHA class ≥ 2
3. NT-proBNP > 900pg/mL (or BNP > 200 pg/mL) or hospitalization for HF within the 2
years;
Note: To account for the decrease in natriuretic peptide levels with
overweight/obesity, NT-proBNP and BNP levels cutoff will be reduced by 4% for every
increase of 1 kg/m2 in BMI above a reference BMI of 20 kg/m2).
4. Under appropriate and stable guideline-directed HF therapy for a minimum of 1 month. o
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.
5. 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.
6. Left ventricular (LV) ejection fraction (EF) < 50% at rest
7. Anatomically suitable for transfemoral TAVR with the SAPIEN 3 or SAPIEN 3 Ultra THV
8. 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)
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
, , [email protected]
Location Countries
Canada
Location Countries
Canada
Administrative Informations
NCT ID
NCT02661451
Organization ID
TAVR Unload
Responsible Party
Sponsor
Study Sponsor
Cardiovascular Research Foundation, New York
Collaborators
Cardialysis BV
Study Sponsor
, ,
Verification Date
March 2020