Transcatheter Aortic Valve Replacement to UNload the Left ventricle in patients with ADvanced heart failure: a randomized trial (TAVR-UNLOAD)

Phase 3

Recruiting

• Conditions: aorta stenose; heart failure; moderate aortic stenosis; 10019280

• Registration Number: NL-OMON54518
• Lead Sponsor: Cardiovascular Research Foundation (CRF)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 23 April 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 56

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 or in case of BSA being elevated due to obesity),
the final eligibility determination in regards to diagnosis of moderate AS will
be made by the echocardiographic core lab.

In indeterminate cases calcium score may also be used to assess the presence of
moderate AS.
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

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 & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Hierarchical occurrence within efficacy assessment time interval (EATI) of:<br /><br>1. All-cause death<br /><br>2. Disabling stroke<br /><br>3. Hospitalizations related to heart failure, symptomatic aortic valve disease<br /><br>or non-disabling stroke<br /><br>-or -<br /><br>4. Clinically significant worsening of heart failure (heart failure<br /><br>hospitalization equivalent).<br /><br>5. Change in KCCQ relative to baseline</p><br>