FORWARD PRO Study Interventional Post-market Study With the Evolut™ PRO System

Study Overview
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Brief Summary
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Prospective, single-arm, multi-center, interventional post-market study. After signing informed consent, eligible subjects will be implanted with the CE marked Evolut™ PRO system. The investigation purpose is to evaluate the acute and long term clinical performance and safety of Evolut™ PRO in a routine hospital setting in patients with symptomatic native aortic valve stenosis or a stenosed, insufficient, or combined surgical bioprosthetic valve failure necessitating valve replacement within the approved intended use in local geography.

Detailed Description
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Approximately 600 subjects implanted with the Evolut™ PRO at up to 40 sites in Europe. Other regions may be added depending on the regulatory status of the device.

Official Title
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FORWARD PRO Study Interventional Post-market Study With the Evolut™ PRO System

Conditions
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Aortic Valve Stenosis

Intervention / Treatment
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* Device: Medtronic CoreValve™ Evolut™ PRO System (Evolut™ PRO System)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptomatic native aortic valve stenosis or a stenosed, insufficient, or combined surgical bioprosthetic valve failure necessitating valve replacement High or greater risk for surgical aortic valve replacement as estimated by the heart team OR, 75 years or older and at intermediate risk for surgical AVR (STS risk score ≥4% or with an estimated hospital mortality ≥4% as assessed by the heart team) Acceptable candidate for treatment with the Evolut™ PRO system in conformity with the Instructions for Use and the local regulations Able and willing to return to the implanting site at the following follow-up visits: 1-year, 3-year and 5-year Written informed consent obtained without assistance from a legal representative prior to enrollment in the study. Exclusion Criteria: Known hypersensitivity or contraindication to aspirin, heparin (HIT/HITTS) and bivalirudin, ticlopidine, clopidogrel, Nitinol (Titanium or Nickel), or sensitivity to contrast media, which cannot be adequately premedicated Preexisting mechanical heart valve in aortic position Ongoing sepsis, including active endocarditis Anatomically not suitable for the Evolut™ PRO system Estimated life expectancy of less than 1 year Participating in another trial that may influence the outcome of this study Need for emergency surgery for any reason Inability to understand and respond to the quality of life questionnaire
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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Arms and Interventions

| Intervention/Treatment |
| --- |
|Device: Medtronic CoreValve™ Evolut™ PRO System (Evolut™ PRO System)|Transcatheter Aortic Valve Replacement with Medtronic Evolut PRO system|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality | The all-cause mortality rate at 30 days post procedure meets a prespecified performance goal of 5.5%. | 30 days post procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total AR | The percentage of subjects graded as none or trace total aortic regurgitation at discharge is greater than a prespecified performance goal of 67.1%. | 24 hours to 7 days post procedure (prior to discharge) | 
| VARC-2 composite safety endpoint | Event rate of the VARC-2 composite safety endpoint through 5 years from enrollment until end of study, which includes the following components: All-cause mortality All stroke (disabling and non-disabling) Life-threatening bleeding Acute kidney injury: stage 2 or 3 (including renal replacement therapy) Coronary artery obstruction requiring intervention Major vascular complication Valve-related dysfunction requiring repeat procedure (BAV, TAVI, or SAVR) | through 5 years from enrollment until end of study | 
| Individual components of the VARC-2 composite safety endpoint | Event rates of the individual components of the VARC-2 composite safety endpoint through 5 years until end of study | through 5 years from enrollment until end of study | 
| Rate of new permanent pacemaker implant | Rate of new permanent pacemaker implant at 30 days post procedure | 30 days post procedure | 
| Device success rate | Device success rate at 24 hours to 7 days post procedure (prior to discharge), defined according to the VARC-2 guidelines as: Absence of procedural mortality, AND Correct positioning of a single prosthetic heart valve into the proper anatomical location, AND Intended performance of the prosthetic heart valve, defined as the absence of patient prosthesis mismatch and mean gradient <20 mmHg (or peak velocity <3 m/sec), AND No moderate or severe prosthetic valve regurgitation. | 24 hours to 7 days post procedure (prior to discharge) | 
| Hemodynamic performance | Hemodynamic performance at 24 hours to 7 days (prior to discharge), 1-year, 3-year and 5-year post procedure, including the mean prosthetic valve gradient as measured by transthoracic echocardiography (TTE) and assessed by an independent core laboratory. | 24 hours to 7 days (prior to discharge), 1-year, 3-year and 5-year post | 
| Hemodynamic performance | Hemodynamic performance at 24 hours to 7 days (prior to discharge), 1-year, 3-year and 5-year post procedure, including the effective orifice area as measured by transthoracic echocardiography (TTE) and assessed by an independent core laboratory. | 24 hours to 7 days (prior to discharge), 1-year, 3-year and 5-year post | 
| Hemodynamic performance | Hemodynamic performance at 24 hours to 7 days (prior to discharge), 1-year, 3-year and 5-year post procedure, including the degree of prosthetic valve regurgitation (transvalvular, paravalvular and total) as measured by transthoracic echocardiography (TTE) and assessed by an independent core laboratory. | 24 hours to 7 days (prior to discharge), 1-year, 3-year and 5-year post | 
| Change in NYHA functional status | Change in NYHA functional status from baseline to 30-day, 1-year, 3-year, and 5-year post procedure | From baseline to 30-day, 1-year, 3-year, and 5-year post procedure | 
| Change in Quality of Life score | Change in Quality of Life score (EQ-5D questionnaire) from baseline to 30-day, and 1-year, 3-year, and 5-year post procedure. The EQ-5D descriptive system comprises five dimensions and each dimension has five levels of severity. The subject is asked to indicate his/her health state by ticking (or placing a cross) in the box against the most appropriate statement in each of the five dimensions. The EQ VAS records the subject's self-rated health on a 20 cm vertical, visual analogue scale. The subject marks an X on the scale to indicate how his/her health is TODAY and then writes the number they marked on the scale in the box below. | From baseline to 30-day, and 1-year, 3-year, and 5-year post procedure |