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

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ClinicalTrials.gov Identifier: NCT02661451
Recruitment Status : Recruiting
First Posted : January 22, 2016
Last Update Posted : March 10, 2020
Sponsor:
Collaborators:
Cardialysis BV
Boston Biomedical Associates LLC
Information provided by (Responsible Party):
Cardiovascular Research Foundation, New York

Tracking Information
First Submitted Date  ICMJE January 15, 2016
First Posted Date  ICMJE January 22, 2016
Last Update Posted Date March 10, 2020
Actual Study Start Date  ICMJE September 2016
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 31, 2019)
  • All-Cause Death [ Time Frame: 12 months ]
    Hierarchical occurrence within efficacy assessment time interval (EATI) of:
  • Disabling Stroke [ Time Frame: 12 months ]
    Hierarchical occurrence within efficacy assessment time interval (EATI) of:
  • Hospitalizations related to heart failure, symptomatic aortic valve disease or non-disabling stroke -or - Clinically significant worsening of heart failure (heart failure hospitalization equivalent). [ Time Frame: 12 months ]
    Hierarchical occurrence within efficacy assessment time interval (EATI) of:
  • Change in KCCQ relative to baseline [ Time Frame: 12 months ]
    Hierarchical occurrence within efficacy assessment time interval (EATI) of:
Original Primary Outcome Measures  ICMJE
 (submitted: January 21, 2016)
  • All-Cause Death within 12 months [ Time Frame: 12 months ]
    Hierarchical occurrence within one year of:
    1. All-cause death
    2. Disabling Stroke
    3. Hospitalizations related to heart failure, symptomatic aortic valve disease or non-disabling stroke
    4. Change in KCCQ relative to baseline
  • Disabling Stroke within 12 months [ Time Frame: 12 months ]
    Hierarchical occurrence within one year of:
    1. All-cause death
    2. Disabling Stroke
    3. Hospitalizations related to heart failure, symptomatic aortic valve disease or non-disabling stroke
    4. Change in KCCQ relative to baseline
  • Hospitalizations related to heart failure, symptomatic aortic valve disease or non-disabling stroke within 12 months [ Time Frame: 12 months ]
    Hierarchical occurrence within one year of:
    1. All-cause death
    2. Disabling Stroke
    3. Hospitalizations related to heart failure, symptomatic aortic valve disease or non-disabling stroke
    4. Change in KCCQ relative to baseline
  • Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) relative to baseline within 12 months [ Time Frame: 12 months ]
    Hierarchical occurrence within one year of:
    1. All-cause death
    2. Disabling Stroke
    3. Hospitalizations related to heart failure, symptomatic aortic valve disease or non-disabling stroke
    4. Change in KCCQ relative to baseline
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 31, 2019)
  • 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: [ Time Frame: 12 month ]
    1. All-cause death
    2. Disabling stroke
    3. Hospitalizations related to heart failure, symptomatic aortic valve disease or non-disabling stroke or clinically significant worsening of heart failure (heart failure event)
  • -All-cause death within EATI [ Time Frame: 12 month ]
    -All-cause death within EATI
Original Secondary Outcome Measures  ICMJE
 (submitted: January 21, 2016)
Composite of all-cause death, disabling stroke and renal replacement therapy at 30 days, 6 months and 12 months [ Time Frame: 30 days, 6 months and 1 year ]
Composite of all-cause death, disabling stroke and renal replacement therapy
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Transcatheter Aortic Valve Replacement to UNload the Left Ventricle in Patients With ADvanced Heart Failure (TAVR UNLOAD)
Official Title  ICMJE 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Aortic Valve Stenosis
Intervention  ICMJE
  • Device: SAPIEN 3 THV
  • Biological: Optimal Heart Failure Therapy
Study Arms  ICMJE
  • Experimental: TAVR (with SAPIEN 3 THV) and OHFT
    Transcatheter heart valve and Optimal Heart Failure Therapy
    Interventions:
    • Device: SAPIEN 3 THV
    • Biological: Optimal Heart Failure Therapy
  • Active Comparator: OHFT
    Optimal Heart Failure Therapy
    Intervention: Biological: Optimal Heart Failure Therapy
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 31, 2019)
300
Original Estimated Enrollment  ICMJE
 (submitted: January 21, 2016)
600
Estimated Study Completion Date  ICMJE March 2022
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Ori Ben Yehuda, MD obenyehuda@crf.org
Contact: Barbara Santiago bsantiago@crf.org
Listed Location Countries  ICMJE Canada,   Netherlands,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02661451
Other Study ID Numbers  ICMJE TAVR Unload
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Cardiovascular Research Foundation, New York
Study Sponsor  ICMJE Cardiovascular Research Foundation, New York
Collaborators  ICMJE
  • Cardialysis BV
  • Boston Biomedical Associates LLC
Investigators  ICMJE Not Provided
PRS Account Cardiovascular Research Foundation, New York
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP