Evaluation of Transcatheter Aortic Valve Replacement Compared to SurveilLance for Patients With AsYmptomatic Severe Aortic Stenosis

Overview

About this study

This clinical trial is a prospective, randomized, controlled, multi-center study. Patients will be randomized 1:1 to receive either transcatheter aortic valve replacement (TAVR) with the Edwards SAPIEN 3 THV or clinical surveillance. Patients will be stratified by whether or not they are able to perform a treadmill stress test. Patients who have a positive stress test will be followed in a registry to collect data on subsequent treatment and mortality, as applicable.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Please contact the study team to discuss whether or not you are eligible to participate in a study.

Inclusion Criteria:

  • 65 years of age or older at time of randomization.
  • Severe AS defined as:
    • AVA ≤1.0 cm2 or AVA index ≤0.6 cm2/m2; AND
    • Peak jet velocity ≥4.0 m/s or Mean gradient ≥40 mmHg.
  • Patient is asymptomatic defined as:
    • Negative treadmill stress test. To be considered asymptomatic, the patient must not demonstrate any of the following during and/or after the test:
      • Syncopal or pre-syncopal episode, including severe dizziness;
      • Angina;
      • Limiting dyspnea or decreased exercise tolerance, defined as inability to reach 60% of age and sex adjusted metabolic equivalents of task (METs);
      • Drop in systolic blood pressure (defined as a progressive drop of at least 20 mmHg and sustained for 1 minute or an acute drop of 40 mmHg);
      • Significant ventricular arrhythmias (≥4 consecutive ventricular premature beats); OR
    • Per physician after thorough assessment of patient history if the patient is unable to perform a stress test.
  • LV ejection fraction ≥50%.
  • Society of Thoracic Surgeons (STS) risk score ≤10.
  • The study patient has been informed of the nature of the study, agrees to its provisions and has provided written informed consent as approved by the institutional review board (IRB) of the respective clinical site.

Exclusion Criteria:

  • Patient is symptomatic (e.g., NYHA Functional Class ≥2, history of syncopal episode, or CCS angina score >1, hospitalization for heart failure within the last 12 months).
  • Patient has any concomitant valvular, aortic, coronary artery disease requiring surgery making AVR a Class I indication.
  • Native aortic annulus size unsuitable for sizes 20, 23, 26, or 29 mm THV based on 3D imaging analysis.
  • Iliofemoral vessel characteristics that would preclude safe placement of the introducer sheath.
  • Left ventricular outflow tract calcification that would increase the risk of annular rupture or significant paravalvular leak (PVL) post TAVR.
  • Evidence of an acute myocardial infarction ≤30 days before randomization.
  • Aortic valve is unicuspid, bicuspid with unfavorable features for TAVR (e.g., aneurysmal ascending aorta, i.e., >4.0 cm; severe or bulky calcification of the LVOT or raphe that would increase the risk of annular injury or significant PVL post TAVR; coronary anatomy that increases the risk of coronary artery obstruction post TAVR), or is non-calcified.
  • Severe aortic regurgitation (>3+).
  • Severe mitral regurgitation (>3+) or ≥moderate mitral stenosis.
  • Pre-existing mechanical or bioprosthetic valve in any position. (Of note, mitral ring is not an exclusion) .
  • Symptomatic carotid or vertebral artery disease or successful treatment of carotid stenosis within 30 days of randomization.
  • Leukopenia (WBC <3000 cell/mL), anemia (Hgb <9 g/dL), thrombocytopenia (Plt <50,000 cell/mL), history of bleeding diathesis or coagulopathy, or hypercoagulable states.
  • Hemodynamic or respiratory instability requiring inotropic support, mechanical ventilation or mechanical heart assistance within 30 days of randomization.
  • Hypertrophic cardiomyopathy with obstruction.
  • Cardiac imaging (echo, Computed Tomography (CT), and/or Magnetic Resonance Imaging (MRI)) evidence of intracardiac mass, thrombus or vegetation.
  • Inability to tolerate or condition precluding treatment with anti-thrombotic therapy.
  • Stroke or transient ischemic attack (TIA) within 90 days of randomization.
  • Renal insufficiency (estimated glomerular filtration rate (eGFR) <30 mL/min per the Cockcroft-Gault formula) and/or renal replacement therapy.
  • Active bacterial endocarditis within 180 days of randomization.
  • Severe lung disease (FEV1 <50% predicted) or currently on home oxygen.
  • Severe pulmonary hypertension (e.g., pulmonary artery (PA) systolic pressure ≥2/3 systemic pressure).
  • History of cirrhosis or any active liver disease.
  • Significant frailty as determined by the Heart Team (after objective assessment of frailty parameters).
  • Significant abdominal or thoracic aortic disease (such as aneurysm, severe calcification, aortic coarctation, etc.) that would preclude safe passage of the delivery system.
  • Patient refuses blood products.
  • BMI >50 kg/m2.
  • Estimated life expectancy <24 months .
  • Absolute contraindications or allergy to iodinated contrast that cannot be adequately treated with pre-medication.
  • Currently participating in an investigational drug or another device study.
    • Note: Trials requiring extended follow-up for products that were investigational, but have since become commercially available, are not considered investigational trials. Observational studies are not considered exclusionary.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

David Holmes, M.D.

Open for enrollment

Contact information:

Pamela Roessler R.N.

(507) 266-4044

Roessler.Pamela@mayo.edu

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20385840

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