Evolut™ EXPAND TAVR II Pivotal Trial

Study Overview
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Brief Summary
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Obtain safety and effectiveness data to support indication expansion for the Medtronic TAVR System to include patients with moderate, symptomatic AS.

Detailed Description
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Multi-center, international, prospective, randomized study. Subjects will be randomized to either transcatheter aortic valve replacement (TAVR) with the Evolut PRO+ TAVR System, or Evolut FX System, and guideline-directed management (GDMT) or GDMT alone.

Official Title
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Evolut™ EXPAND TAVR II Pivotal Trial

Conditions
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Aortic Stenosis Symptomatic, Moderate Aortic Valve Stenosis

Intervention / Treatment
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* Device: Medtronic Evolut PRO+ TAVR System, or Evolut FX TAVR System, and guideline-directed management and therapy (GDMT)


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: • Moderate AS, defined as follows by transthoracic echo (TTE) as assessed by the ECL: AVA >1.0 cm² and < 1.5 cm² and Max aortic velocity ≥ 3.0 m/sec and < 4.0 m/sec, OR mean aortic gradient ≥ 20.0 mmHg and < 40.0 mmHg, • Symptoms of AS, defined as NYHA ≥ Class II, or Reduced functional capacity, defined as 6MWT < 300 meters, or < 85% of age-sex predicted METs on exercise tolerance testing (ETT) • Any of the following HF event or hospitalization for heart failure within 1 calendar year prior to consent NT-proBNP ≥ 600 pg/ml (or BNP ≥ 80 pg/ml), Persistent AF or Paroxysmal AF episode within 6 months prior to consent, or Elevated aortic valve calcium score (>1200 AU for females and > 2000 AU for males) as assessed by the MDCT core lab, or Any of the following by the qualifying TTE as assessed by the ECL: Global longitudinal strain ≤16% (absolute value) E/e' ≥ 14.0 (average of medial and lateral velocities), or Diastolic dysfunction ≥ Grade II LVEF < 60% Stroke Volume Index < 35 ml/m² Anatomically suitable for transfemoral RAVR using the Medtronic Evolut PRO+ or Evolut FX system The subject and the treating physician agree the subject will return for all required follow-up visits Key Exclusion Criteria: Age < 65 years LVEF ≤ 20% by 2-D echo Class I indication for cardiac surgery Sievers Type 0 or Type 2 bicuspid aortic valve or Sievers Type 1 bicuspid aortic valve with ascending aorta diameter > 4.5 cm Not anatomically suitable for transfemoral TAVR with the trial device In need of and suitable for coronary revascularization per Heart Valve Team Documented history of cardiac amyloidosis

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Medtronic Evolut PRO+, or Evolut FX,TAVR System, & guideline-directed management & therapy (GDMT)<br>Medtronic Evolut PRO+ TAVR or Evolut FX TAVR Systems, & guideline-directed management & therapy | Device: Medtronic Evolut PRO+ TAVR System, or Evolut FX TAVR System, and guideline-directed management and therapy (GDMT)<br>* Patients will have a Transcatheter Aortic Valve Replacement (TAVR) with either an Evolut PRO+ TAVR, or Evolut FX TAVR, heart valve, and given clinical site-determined guideline-directed management and therapy (GDMT).<br>|
| No Intervention: Clinical site determined guideline-directed management and therapy (GDMT) alone<br>Clinical site determined guideline-directed management and therapy (GDMT) alone | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite rate of all-cause mortality, all-stroke, life threatening or fatal bleeding, acute kidney injury, hospitalization due to device or procedure-related complication, or valve dysfunction requiring reintervention. | Life threatening or fatal bleeding is defined as BARC Type 3 or 4 and acute kidney injury is defined as VARC-3 Stage IV. | 30 days | 
| Composite rate of all-cause mortality, heart failure hospitalization or event, or medical instability leading to aortic valve replacement or re-intervention. |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects alive and with moderately improved quality of life (≥ 10 points in KCCQ summary score from baseline) |  | 1 year | 
| Composite of all-cause mortality and heart failure hospitalizations or events. |  | 2 years | 
| Composite of all-cause mortality, all-stroke, or unplanned CV hospitalizations |  | 2 years | 
| Heart failure hospitalizations or events. |  | 2 years | 
| All-cause mortality |  | 2 years | 
| Unplanned cardiovascular hospitalizations |  | 2 years | 
| Days alive and free of unplanned cardiovascular hospitalizations |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aortic, stenosis, symptomatic, moderate, valve, TAVR