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

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 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

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