CoreValve™ Evolut R™ FORWARD Study

Study Overview
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Brief Summary
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Prospective, single arm, multi-center, observational, post market study to document the clinical and device performance outcomes of the Evolut R system used in routine hospital practice in a large patient cohort for the treatment of symptomatic native aortic valve stenosis or a stenosed, insufficient, or combined surgical bioprosthetic valve failure necessitating valve replacement.

Detailed Description
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The study objective is to document the clinical and device performance outcomes of the Evolut R system used in routine hospital practice in a large patient cohort for the treatment of symptomatic native aortic valve stenosis or a stenosed, insufficient, or combined surgical bioprosthetic valve failure necessitating valve replacement. Prospective, single arm, multi-center, observational, post market study. In Australia and Canada it is a prospective, single arm, multi-center pre-market study. Up to 60 centers worldwide. Geographies may include Europe, Australia, Middle East and Africa, Latin America and Canada. Approximately 1000 implanted subjects, consented for follow-up through three years. For each subject, data will be collected preoperatively, intra-operatively, at hospital discharge, 30 days, 1, 2 and 3 years.

Official Title
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The Medtronic CoreValve™ Evolut R™ FORWARD Study

Conditions
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Aortic Valve Stenosis

Intervention / Treatment
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* Device: Medtronic CoreValve™ Evolut R™ 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 Acceptable candidate for elective treatment with the Evolut R System and in conformity with the local regulatory and medico economic context Age ≥80 years OR considered to be at high or greater risk for surgical aortic valve replacement (AVR) where high risk is defined as: Society of Thoracic Surgeons (STS) predicted risk of mortality ≥8% OR Documented heart team agreement of risk for AVR due to frailty or comorbidities. Geographically stable and willing to return to the implanting site for all follow-up visits Of legal age to provide informed consent (patient Informed Consent or Data Release Form) in the country where they enroll in the trial The patient has been informed of the nature of the study, is able and willing to provide consent without assistance from a legal representative and has consented to participate, and has authorized the collection and release of his/her medical information by signing a Patient Informed Consent or Data Release Form. 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 R system Estimated life expectancy of less than 1 year Participating in another trial that may influence the outcome of this trial Need for emergency surgery for any reason
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 R™ System|The Evolut R System is intended for relief of aortic stenosis in patients with symptomatic heart disease due to severe native calcific aortic stenosis who are judged by a heart team, to be at high or extreme risk for open heart surgery. The Evolut R TAV treats aortic stenosis by displacing and functionally replacing the dysfunctional native valve with a bioprosthetic valve delivered on a catheter while the heart is still beating, thus avoiding the risks of cardiopulmonary bypass. Its intended performance is to relieve aortic valve stenosis without inducing significant regurgitation, thereby restoring effective aortic valve function.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality rate | All-cause mortality rate at 30 days post procedure | 30 days post implant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Device success according to VARC2 | Device success rate at 24 hours to 7 days, defined according to the Valve Academic Research Consortium-2 (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. | 24h to 7 days post implant | 
| Hemodynamic performance | Hemodynamic performance at 24 hours to 7 days (discharge) and 1 year post procedure, including the mean prosthetic valve gradient as measured by transthoracic echocardiography (TTE) and assessed by an independent core laboratory. | 24h to 7 days and 1 year post implant | 
| Hemodynamic performance | Hemodynamic performance at 24 hours to 7 days (discharge) and 1 year post procedure, including the effective orifice area as measured by transthoracic echocardiography (TTE) and assessed by an independent core laboratory. | 24h to 7 days and 1 year post implant | 
| Hemodynamic performance | Hemodynamic performance at 24 hours to 7 days (discharge) and 1 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. | 24h to 7 days and 1 year post implant | 
| Early safety composite endpoint according to VARC2 | Early Safety composite endpoint at 30 days post procedure, defined according to the VARC-2 guidelines, defined as any of 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) | 30 days post implant | 
| Event rates according to VARC2 | Event rates of the individual components of the VARC-2 composite Early Safety endpoint at 30 days post procedure | 30 days post implant | 
| Rate of new permanent pacemaker implant | Rate of new permanent pacemaker implant at 30 days post procedure | 30 days post implant |