Symptomatic Aortic Stenosis
Conditions
Brief summary
The purpose of this study is to collect clinical evidence on valve performance and procedural outcomes associated with an optimized TAVR care pathway and post-TAVR conduction disturbance pathway while using the Evolut™ PRO and Evolut™ PRO+ devices. The purpose of the addendum is to collect post-market clinical evidence on valve performance and procedural outcomes associated with the Evolut FX Device.
Detailed description
This is a post market, multi-center (sites in US/CAN/EMEA/ANZ), prospective, non-randomized study. The addendum is a post market, multi-center (sites in US only), prospective, non-randomized study.
Interventions
DEVICEEvolut™ PRO and Evolut™ PRO+ System (Evolut™ FX System for the addendum)
Aortic valve replacement
Sponsors
Medtronic Cardiovascular
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Acceptable candidate for treatment with the Evolut™ PRO or Evolut™ PRO+ system (FX system for the addendum where applicable) in accordance with the Instructions for Use and local regulations; * Subject is symptomatic from his/her aortic valve stenosis, as demonstrated by New York Heart Association (NYHA) Functional Class II or greater; * Subject and the treating physician agree that the subject will return for all required post procedure follow-up visits; * Anatomically suitable for transfemoral TAVR with the Medtronic TAVR system; * Subject meets the legal minimum age to provide Informed Consent based on local regulatory requirements.
Exclusion criteria
* Contraindicated for treatment with the Evolut™ PRO or Evolut™ PRO+ or FX system (where applicable) in accordance with the Instructions for Use * Anatomically not suitable for the Evolut™ PRO or Evolut™ PRO+ or FX system (where applicable); * Previous aortic valve replacement * Reduced ventricular function with left ventricular ejection fraction (LVEF) \<35% as measured by resting echocardiogram; * Frailty assessments identify: * Subject is \<80 years of age and three or more of the following apply; OR subject is \> 80 years of age and two or more of the following apply * Wheelchair bound * Resides in an institutional care facility (e.g. nursing home, skilled care center) * Body Mass Index \<20kg/m2 * Grip strength \<16kg * Katz Index score ≤4 * Albumin \<3.5 g/dL * Bicuspid valve verified; * Aortic root angulation (angle between plane of aortic valve annulus and horizontal plane/vertebrae) \> 70°. * Implanted with pacemaker or ICD; * Prohibitive left ventricular outflow tract calcification; * Estimated life expectancy of less than 12 months due to associated non- cardiac co-morbid conditions; * Other medical, social, or psychological conditions that in the opinion of the Investigator precludes the subject from appropriate consent, adherence to the protocol required follow-up exams; * Currently participating in an investigational drug or another device trial (excluding registries); * Need for emergency surgery for any reason. * Subject is less than legal age of consent, legally incompetent, or otherwise vulnerable\*. * Notes: Vulnerable subjects include individuals whose willingness to volunteer in a clinical investigation could be unduly influenced by the expectation, whether justified or not, of benefits associated with participation or of retaliatory response from senior members of a hierarchy in case of refusal to participate. EXAMPLE Individuals with lack of or loss of autonomy due to immaturity or through mental disability, persons in nursing homes, children, impoverished persons, subjects in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, and those incapable of giving informed consent. Other vulnerable subjects include, for example, members of a group with a hierarchical structure such as university students, subordinate hospital and laboratory personnel, employees of the sponsor, members of the armed forces, and persons kept in detention.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| All-cause Mortality or All-stroke | 30 days post procedure | All-cause mortality or all-stroke at 30 days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Length of Stay | Through discharge up to 7 days post index procedure. | Median days from index procedure to discharge |
| Aortic Regurgitation (AR) | Through discharge up to 7 days post index procedure. | Percentage of subjects with ≥ moderate AR at discharge |
| Pacemaker Implantation or Worsening Conduction Disturbance | 30 days | Rate of pacemaker implant for new onset or worsening conduction disturbance at 30 days |
| Depth of Implant (Evolut FX Only) | 30 days | Percentage of subjects with a Non-Coronary Cusp (NCC) depth of implant between 1.0 and 5.0 mm (Evolut FX Addendum Only) |
| Canting (Evolut FX Addendum Only) | 30 Days | Percentage of subjects with a canting absolute value \[NCC- Left Coronary Cusp(LCC)\] of ≤ 2.0 mm (Evolut FX Addendum Only) |
Countries
Australia, Belgium, Canada, France, Germany, Ireland, Israel, Italy, Spain, Sweden, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Main Protocol Evolut™ PRO and Evolut™ PRO+ System: Aortic valve replacement | 653 |
| FX Addendum Evolut™ FX System: Aortic valve replacement | 151 |
| Total | 804 |
Baseline characteristics
| Characteristic | FX Addendum | Total | Main Protocol |
|---|---|---|---|
| Age, Continuous FX Addendum Cohort | 78.3 years STANDARD_DEVIATION 7.1 | 78.3 years STANDARD_DEVIATION 7.1 | — |
| Age, Continuous Main Protocol | — | 79.1 years STANDARD_DEVIATION 6.5 | 79.1 years STANDARD_DEVIATION 6.5 |
| Body Mass Index (BMI) FX Addendum | 30.2 kg/m^2 STANDARD_DEVIATION 6 | 30.2 kg/m^2 STANDARD_DEVIATION 6 | — |
| Body Mass Index (BMI) Main Protocol | — | 29.6 kg/m^2 STANDARD_DEVIATION 5.9 | 29.6 kg/m^2 STANDARD_DEVIATION 5.9 |
| NYHA FX Addendum NYHA I | 1 Participants | 1 Participants | — |
| NYHA FX Addendum NYHA II | 110 Participants | 110 Participants | — |
| NYHA FX Addendum NYHA III | 38 Participants | 38 Participants | — |
| NYHA FX Addendum NYHA IV | 2 Participants | 2 Participants | — |
| NYHA Main Protocol NYHA I | — | 0 Participants | 0 Participants |
| NYHA Main Protocol NYHA II | — | 374 Participants | 374 Participants |
| NYHA Main Protocol NYHA III | — | 256 Participants | 256 Participants |
| NYHA Main Protocol NYHA IV | — | 23 Participants | 23 Participants |
| Race/Ethnicity, Customized FX Addendum American Indian or Alaska Native | 1 Participants | 1 Participants | — |
| Race/Ethnicity, Customized FX Addendum Asian | 0 Participants | 0 Participants | — |
| Race/Ethnicity, Customized FX Addendum Black or African American | 6 Participants | 6 Participants | — |
| Race/Ethnicity, Customized FX Addendum Native Hawaiian or Other Pacific Islander | 2 Participants | 2 Participants | — |
| Race/Ethnicity, Customized FX Addendum Other | 1 Participants | 1 Participants | — |
| Race/Ethnicity, Customized FX Addendum White | 141 Participants | 141 Participants | — |
| Race/Ethnicity, Customized Main Protocol American Indian or Alaska Native | — | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Main Protocol Asian | — | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Main Protocol Black or African American | — | 11 Participants | 11 Participants |
| Race/Ethnicity, Customized Main Protocol Native Hawaiian or Other Pacific Islander | — | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Main Protocol Other | — | 5 Participants | 5 Participants |
| Race/Ethnicity, Customized Main Protocol White | — | 432 Participants | 432 Participants |
| Sex: Female, Male FX Addendum Female | 67 Participants | 67 Participants | — |
| Sex: Female, Male FX Addendum Male | 84 Participants | 84 Participants | — |
| Sex: Female, Male Main Protocol Female | — | 307 Participants | 307 Participants |
| Sex: Female, Male Main Protocol Male | — | 346 Participants | 346 Participants |
| STS Score FX Addendum | 3.1 Mean STANDARD_DEVIATION 2 | 3.1 Mean STANDARD_DEVIATION 2 | — |
| STS Score Main Protocol | — | 3.3 Mean STANDARD_DEVIATION 2.3 | 3.2 Mean STANDARD_DEVIATION 2.5 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 32 / 653 | 7 / 151 |
| other Total, other adverse events | 0 / 653 | 0 / 151 |
| serious Total, serious adverse events | 212 / 653 | 44 / 151 |
Outcome results
Primary
All-cause Mortality or All-stroke
All-cause mortality or all-stroke at 30 days.
Time frame: 30 days post procedure
Population: The attempted implant set was the basis for the primary outcome measure for the Main Protocol and FX Addendum.~The attempted implant set consists of all enrolled subjects with an attempted TAVR implant procedure, defined as when the subject is brought into the procedure room and any of the following have occurred: anesthesia or conscious sedation administered, vascular line placed, TEE placed, or any monitoring line placed.~Main Protocol and FX Addendum results are analyzed separately.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Protocol | All-cause Mortality or All-stroke | 5.1 Percent of Participants (K-M Rate) |
| FX Addendum | All-cause Mortality or All-stroke | 2.7 Percent of Participants (K-M Rate) |
Secondary
Aortic Regurgitation (AR)
Percentage of subjects with ≥ moderate AR at discharge
Time frame: Through discharge up to 7 days post index procedure.
Population: The implanted set was the basis for the AR secondary outcome measure for both the Main Protocol and FX Addendum.~The implanted set consists of all the attempted implant subjects who are actually implanted with the Medtronic TAV device.~Main Protocol and FX Addendum results are analyzed separately.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Main Protocol | Aortic Regurgitation (AR) | 0 Participants |
| FX Addendum | Aortic Regurgitation (AR) | 0 Participants |
Secondary
Canting (Evolut FX Addendum Only)
Percentage of subjects with a canting absolute value \[NCC- Left Coronary Cusp(LCC)\] of ≤ 2.0 mm (Evolut FX Addendum Only)
Time frame: 30 Days
Population: The FX Addendum implanted set was the basis for the canting outcome measure.~The implanted set consists of all attempted implant subjects who are actually implanted with the Medtronic Evolut™ FX device.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Main Protocol | Canting (Evolut FX Addendum Only) | 59 Participants |
Secondary
Depth of Implant (Evolut FX Only)
Percentage of subjects with a Non-Coronary Cusp (NCC) depth of implant between 1.0 and 5.0 mm (Evolut FX Addendum Only)
Time frame: 30 days
Population: The FX Addendum implanted set was the basis for the depth of implant outcome measure.~The implanted set consists of all attempted implant subjects who are actually implanted with the Medtronic Evolut™ FX device.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Main Protocol | Depth of Implant (Evolut FX Only) | 83 Participants |
Secondary
Length of Stay
Median days from index procedure to discharge
Time frame: Through discharge up to 7 days post index procedure.
Population: The basis for the length of stay secondary outcome measure was the per-protocol (PP) set 1 for TAVR care pathway for the Main Protocol and the attempted implant set for the FX Addendum.~PP set 1 for TAVR care pathway consists of all implanted subjects with percutaneous and transfemoral access only and no concomitant procedures including percutaneous coronary intervention.~Main Protocol and FX Addendum results are analyzed separately.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Main Protocol | Length of Stay | 2.0 Days |
| FX Addendum | Length of Stay | 1.0 Days |
Secondary
Pacemaker Implantation or Worsening Conduction Disturbance
Rate of pacemaker implant for new onset or worsening conduction disturbance at 30 days
Time frame: 30 days
Population: The basis for the pacemaker implantation or worsening conduction disturbance secondary outcome measure was the PP set 2 for the Main Protocol and the attempted implant set for the FX Addendum.~PP set 2 for conduction disturbance pathway set consists of all attempted implant subjects whose peri- and post-TAVR index procedure follows the conduction disturbance pathway management and cusp overlap technique.~Main Protocol and FX Addendum results are analyzed separately.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Protocol | Pacemaker Implantation or Worsening Conduction Disturbance | 6.5 Percent of Participants (K-M Rate) |
| FX Addendum | Pacemaker Implantation or Worsening Conduction Disturbance | 6.7 Percent of Participants (K-M Rate) |