Symptomatic Severe Aortic Stenosis
Conditions
Keywords
Aortic Stenosis, FlexNav™ Delivery System, Portico Delivery System, Transcatheter Aortic Valve Replacement, Heart Valve Disease, High surgical risk
Brief summary
The purpose of this clinical investigation is to characterize the safety of the next-generation FlexNav™ Delivery System for transfemoral implantation of the Portico™ Transcatheter Aortic Heart Valve in symptomatic severe aortic stenosis patients who are considered of high or extreme risk for surgical aortic valve replacement. Data from the study will be used to support CE Mark of the FlexNav™ Delivery System and Loading System in Europe.
Detailed description
The FlexNav European Union (EU) study will be conducted as a prospective, multi-center, single-arm investigational study. High or extreme risk patients with symptomatic, severe native aortic stenosis who are determined by an independent subject selection committee to meet eligibility criteria for Portico™ Transcatheter Aortic Heart Valve implantation via a transfemoral access approach will undergo a Portico valve implant using the next-generation FlexNav Delivery System. Subject data will be collected at screening, baseline, pre-procedure, peri-procedure, post-procedure, discharge, 30 days, 6 months and 1-year from the index procedure.
Interventions
DEVICEPortico Valve and FlexNav™ Delivery System
Subjects will undergo transcatheter aortic valve replacement (TAVR) with the Portico valve and second-generation FlexNav Delivery system via a transfemoral access approach
Sponsors
Abbott Medical Devices
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Devices under investigation in this clinical investigation include the FlexNav™ Delivery System(s) (18 F and 19 F) and FlexNav™ Loading System(s) (Small and Large), which are both approved for investigational use only. Other devices to be used in the clinical investigation include all four (4) market released Abbott Portico™ valve sizes (23mm, 25mm, 27mm and 29mm).
Eligibility
Sex/Gender
ALL
Age
21 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
\- Candidates for High Risk classification must meet all the following inclusion criteria: 1. Subjects must have co-morbidities such that the local heart team concur the predicted risk of operative mortality is ≥15% or a minimum Society of Thoracic Surgeons (STS) score of 8%. a) A candidate who does not meet the STS score criteria of ≥ 8% may be included in the study if at least one surgeon in the local heart team concludes and documents the patient's predicted risk of operative mortality is ≥15%. The surgeon's assessment of operative comorbidities (including frailty indices) not captured by the STS score must be documented in the study case report form as well as in the patient medical record. 2. Subject is of legal age or older for consent in the host country. 3. Subject has senile degenerative aortic valve stenosis with echo-derived criteria: mean gradient \>40 mmHg or jet velocity greater than 4.0 m/s or doppler velocity index (DVI) \<0.25 and an initial aortic valve area (AVA) of ≤1.0 cm2 (indexed Effective Orifice Area (EOA) ≤ 0.6 cm2/m2). (Qualifying AVA baseline measurement must be within 60 days prior to informed consent). 4. Subject has symptomatic aortic stenosis as demonstrated by NYHA Functional Classification of II, III, or IV. 5. The subject 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. 6. The subject and the treating physician agree that the subject will return for all required post-procedure follow-up visits. 7. Subject's aortic annulus is 19-27mm diameter as measured by computed tomography (CT) conducted within 12 months prior to informed consent. If a CT i contraindicated and/or not possible to be obtained for certain subjects, a 3D echo and non-contrast CT of chest and abdomen/pelvis may be accepted. All candidates for Extreme Risk classification must meet # 2, 3, 4, 5, 6, 7 of the above criteria, and 8. After formal consultation with the local heart team (including at least one surgeon) it is agreed that medical factors preclude the subject from undergoing operation, based on a conclusion that the probability of death or serious, irreversible morbidity exceeds the probability of meaningful improvement. Specifically, the probability of death or serious, irreversible morbidity should exceed 50%. The local heart teams' consult notes shall specify the medical or anatomic factors leading to that conclusion and include a printout of the calculation of the STS score to additionally identify the risks in these patients.
Exclusion criteria
Candidates will be excluded if any of the following conditions are present: 1. Evidence of an acute myocardial infarction (defined as: ST Segment Elevation as evidenced on 12 Lead ECG) within 30 days prior to index procedure. 2. Aortic valve is a congenital unicuspid or congenital bicuspid valve, or is noncalcified as verified by echocardiography. 3. Mixed aortic valve disease (aortic stenosis and aortic regurgitation with predominant aortic regurgitation 3-4+). 4. Any percutaneous coronary or peripheral interventional procedure performed within 30 days prior to index procedure. 5. Pre-existing prosthetic heart valve or other implant in any valve position, prosthetic ring, severe circumferential mitral annular calcification (MAC) which is continuous with calcium in the LVOT, severe (greater than 3+) mitral insufficiency, or severe mitral stenosis with pulmonary compromise. 6. Blood dyscrasias as defined: leukopenia (WBC\<3000 mm3), acute anemia (Hb \< 9 g/dL), thrombocytopenia (platelet count \<50,000 cells/mm³). 7. History of bleeding diathesis or coagulopathy. 8. Cardiogenic shock manifested by low cardiac output, vasopressor dependence, or mechanical hemodynamic support. 9. Untreated clinically significant coronary artery disease requiring revascularization. 10. Hemodynamic instability requiring inotropic support or mechanical heart assistance. 11. Need for emergency surgery for any reason. 12. Hypertrophic cardiomyopathy with or without obstruction (HOCM). 13. Severe ventricular dysfunction with left ventricular ejection fraction (LVEF) \<20% as measured by resting echocardiogram. 14. Echocardiographic evidence of intracardiac mass, thrombus or vegetation. 15. Active peptic ulcer or upper GI bleeding within 3 months prior to index procedure. 16. A known hypersensitivity or contraindication to aspirin, heparin, ticlopidine (Ticlid), or clopidogrel (Plavix), or sensitivity to contrast media which cannot be adequately premedicated. 17. Recent (within 6 months prior to index procedure date) cerebrovascular accident (CVA) or a transient ischemic attack (TIA). 18. Renal insufficiency (creatinine \> 3.0 mg/dL) and/or end stage renal disease requiring chronic dialysis. 19. Life expectancy \< 12 months from the time of informed consent due to noncardiac co-morbid conditions. 20. Significant aortic disease, including abdominal aortic or thoracic aneurysm defined as maximal luminal diameter 5cm or greater; marked tortuosity (hyperacute bend), aortic arch atheroma (especially if thick \[\> 5 mm\], protruding or ulcerated) or narrowing (especially with calcification and surface irregularities) of the abdominal or thoracic aorta, severe unfolding and tortuosity of the thoracic aorta. 21. Native aortic annulus size \< 19 mm or \> 27 mm per the baseline diagnostic imaging. 22. Aortic root angulation \> 70°. 23. Currently participating in an investigational drug or device study. 24. Active bacterial endocarditis within 6 months prior to the index procedure. 25. Bulky calcified aortic valve leaflets in close proximity to coronary ostia. 26. Non-calcified aortic annulus. 27. Iliofemoral vessel characteristics that would preclude safe insertion of the FlexNav™ delivery system with or without an arterial introducer sheath such as severe obstructive calcification, or severe tortuosity. 28. In the judgment of the investigator, a condition that could limit a patient's ability or willingness to participate in the study, comply with study required testing and/or follow- up visits or that could impact scientific integrity of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major Vascular Complications | At 30 days post index procedure | Percentage of patients with a VARC-2 defined major vascular complication event |
Other
| Measure | Time frame | Description |
|---|---|---|
| All-Cause Mortality | 30 days from the index procedure | Percentage of patients with VARC 2 defined all-cause mortality |
| Disabling Stroke | 30 days from index procedure | Percentage of patients with a VARC-2 defined disabling stroke event |
| Life-threatening Bleeding Requiring Blood Transfusion | 30 days from the index procedure | Percentage of patients with a VARC-2 defined life-threatening bleeding event requiring blood transfusion |
| Major Bleeding Event | 30 days from index procedure | Percentage of patients with VARC 2 defined major bleeding event |
| Acute Kidney Injury | 30 days from index procedure | Percentage of patients with a VARC 2 defined acute kidney injury event |
| Minor Vascular Complication | 30 days from index procedure | Percentage of patients with a VARC-2 defined minor vascular complication |
| Non-hierarchical Composite Safety Endpoint | 30 days from the index procedure. | Percentage of patients with a non-hierarchical composite endpoint of all-cause mortality, disabling stroke, life threatening bleeding requiring blood transfusion, acute kidney injury requiring dialysis, or major vascular complications |
| Severity of Paravalvular Leak | 30 days from index procedure | Echocardiographic core-laboratory derived severity of paravalvular leak |
| NYHA Functional Classification | 30 days from index procedure | Proportion of subjects with a NYHA Functional Class of I,II, III or IV (range I-IV where a lower score indicates less limitation in physical activity) |
| Kansas City Cardiomyopathy Questionnaire Quality of Life (QOL) Score | 30 days from index procedure | KCCQ Overall summary score (range 0-100 where a higher score indicates a better quality of life and physical function) |
| Technical Device Success | Over the duration of index procedure, an average of 60.6 minutes | Technical device success defined as successful vascular access, delivery and deployment of the Portico Valve; retrieval with the delivery system and correct positioning of a single valve in the proper anatomical location. |
| All-Cause Mortality or Disabling Stroke | One year (365 days) from index procedure | Percentage of patients with a composite of all-cause mortality or disabling stroke at one year from the index procedure censored for COVID-19 related events |
| New Permanent Pacemaker Implant | 30 days from index procedure | Percentage of patients requiring a new permanent pacemaker. Excludes patients with a pre-existing permanent pacemaker at baseline |
Countries
Denmark, Italy, Switzerland, United Kingdom
Participant flow
Recruitment details
Patients were enrolled between 26 February 2019 and 10 December 2019
Participants by arm
| Arm | Count |
|---|---|
| Portico Valve and FlexNav™ Delivery System Subjects will undergo an attempted transcatheter aortic valve replacement (TAVR) with the Portico valve and next-generation FlexNav Delivery system via a transfemoral access approach | 46 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 2 |
| Overall Study | Missed Visit | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Portico Valve and FlexNav™ Delivery System | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 46 Participants | — |
| Age, Categorical Between 18 and 65 years | 0 Participants | — |
| Age, Continuous | 85.4 years STANDARD_DEVIATION 4.9 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment Denmark | 3 participants | — |
| Region of Enrollment Italy | 17 participants | — |
| Region of Enrollment Switzerland | 4 participants | — |
| Region of Enrollment United Kingdom | 22 participants | — |
| Sex: Female, Male Female | 33 Participants | — |
| Sex: Female, Male Male | 13 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 46 |
| other Total, other adverse events | 19 / 46 |
| serious Total, serious adverse events | 21 / 46 |
Outcome results
Primary
Major Vascular Complications
Percentage of patients with a VARC-2 defined major vascular complication event
Time frame: At 30 days post index procedure
Population: Analysis population included all subjects in whom a Portico valve implant was attempted (enrolled subjects)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Portico Valve and FlexNav™ Delivery System | Major Vascular Complications | 4.3 percentage of participants |
Other Pre-specified
Acute Kidney Injury
Percentage of patients with a VARC 2 defined acute kidney injury event
Time frame: 30 days from index procedure
Population: Analysis population included all subjects in whom a Portico valve implant was attempted (enrolled subjects)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Portico Valve and FlexNav™ Delivery System | Acute Kidney Injury | 0 percentage of participants |
Other Pre-specified
All-Cause Mortality
Percentage of patients with VARC 2 defined all-cause mortality
Time frame: 30 days from the index procedure
Population: Analysis population included all subjects in whom a Portico valve implant was attempted (enrolled subjects)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Portico Valve and FlexNav™ Delivery System | All-Cause Mortality | 0 percentage of participants |
Other Pre-specified
All-Cause Mortality
Percentage of patients that died at one year from the index procedure censored for COVID-19 related endpoint events
Time frame: One year (365 days) from index procedure
Population: sensitivity analyses censoring subject's first COVID-19 related endpoint event
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Portico Valve and FlexNav™ Delivery System | All-Cause Mortality | 2.2 percentage of participants |
Other Pre-specified
All-Cause Mortality or Disabling Stroke
Percentage of patients with a composite of all-cause mortality or disabling stroke at one year from the index procedure censored for COVID-19 related events
Time frame: One year (365 days) from index procedure
Population: sensitivity analyses censoring subject's first COVID-19 related endpoint event
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Portico Valve and FlexNav™ Delivery System | All-Cause Mortality or Disabling Stroke | 2.2 percentage of participants |
Other Pre-specified
Disabling Stroke
Percentage of patients with a VARC-2 defined disabling stroke event
Time frame: 30 days from index procedure
Population: Analysis population included all subjects in whom a Portico valve implant was attempted (enrolled subjects)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Portico Valve and FlexNav™ Delivery System | Disabling Stroke | 0 percentage of participants |
Other Pre-specified
Disabling Stroke
Percentage of patients with a disabling stroke at one year from index procedure censored for COVID-19 related endpoint events
Time frame: One Year (365 days) from index procedure
Population: sensitivity analyses censoring subject's first COVID-19 related endpoint event
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Portico Valve and FlexNav™ Delivery System | Disabling Stroke | 0 percentage of participants |
Other Pre-specified
Kansas City Cardiomyopathy Questionnaire Quality of Life (QOL) Score
KCCQ Overall summary score (range 0-100 where a higher score indicates a better quality of life and physical function)
Time frame: 30 days from index procedure
Population: Analysis population included all subjects in whom a Portico valve implant was attempted (enrolled subjects). Information was not available for 2 subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Portico Valve and FlexNav™ Delivery System | Kansas City Cardiomyopathy Questionnaire Quality of Life (QOL) Score | 66.46 score on a scale | Standard Deviation 20.86 |
Other Pre-specified
Kansas City Cardiomyopathy Questionnaire Quality of Life (QOL) Score
KCCQ Overall summary score (range 0-100 where a higher score indicates a better quality of life and physical function)
Time frame: One year from index procedure
Population: Analysis population included all subjects in whom a Portico valve implant was attempted (enrolled subjects). Information was not available for 2 subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Portico Valve and FlexNav™ Delivery System | Kansas City Cardiomyopathy Questionnaire Quality of Life (QOL) Score | 71.11 score on a scale | Standard Deviation 16.71 |
Other Pre-specified
Life-threatening Bleeding Requiring Blood Transfusion
Percentage of patients with a VARC-2 defined life-threatening bleeding event requiring blood transfusion
Time frame: 30 days from the index procedure
Population: Analysis population included all subjects in whom a Portico valve implant was attempted (enrolled subjects)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Portico Valve and FlexNav™ Delivery System | Life-threatening Bleeding Requiring Blood Transfusion | 4.3 percentage of participants |
Other Pre-specified
Major Bleeding Event
Percentage of patients with VARC 2 defined major bleeding event
Time frame: 30 days from index procedure
Population: Analysis population included all subjects in whom a Portico valve implant was attempted (enrolled subjects)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Portico Valve and FlexNav™ Delivery System | Major Bleeding Event | 4.3 percentage of participants |
Other Pre-specified
Minor Vascular Complication
Percentage of patients with a VARC-2 defined minor vascular complication
Time frame: 30 days from index procedure
Population: Analysis population included all subjects in whom a Portico valve implant was attempted (enrolled subjects)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Portico Valve and FlexNav™ Delivery System | Minor Vascular Complication | 15.2 percentage of participants |
Other Pre-specified
New Permanent Pacemaker Implant
Percentage of patients requiring a new permanent pacemaker. Excludes patients with a pre-existing permanent pacemaker at baseline
Time frame: 30 days from index procedure
Population: Analysis population included all subjects in whom a Portico valve implant was attempted (enrolled subjects) and who did not have a pre-existing pacemaker at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Portico Valve and FlexNav™ Delivery System | New Permanent Pacemaker Implant | 14.3 percentage of participants |
Other Pre-specified
Non-hierarchical Composite Safety Endpoint
Percentage of patients with a non-hierarchical composite endpoint of all-cause mortality, disabling stroke, life threatening bleeding requiring blood transfusion, acute kidney injury requiring dialysis, or major vascular complications
Time frame: 30 days from the index procedure.
Population: Analysis population included all subjects in whom a Portico valve implant was attempted (enrolled subjects)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Portico Valve and FlexNav™ Delivery System | Non-hierarchical Composite Safety Endpoint | 6.5 percentage of subjects |
Other Pre-specified
NYHA Functional Classification
Proportion of subjects with a NYHA Functional Class of I,II, III or IV (range I-IV where a lower score indicates less limitation in physical activity)
Time frame: 30 days from index procedure
Population: Analysis population included all subjects in whom a Portico valve implant was attempted (enrolled subjects). Information was not available for one subject.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Portico Valve and FlexNav™ Delivery System | NYHA Functional Classification | NYHA I | 48.9 percentage of participants |
| Portico Valve and FlexNav™ Delivery System | NYHA Functional Classification | NYHA II | 48.9 percentage of participants |
| Portico Valve and FlexNav™ Delivery System | NYHA Functional Classification | NYHA III | 2.2 percentage of participants |
| Portico Valve and FlexNav™ Delivery System | NYHA Functional Classification | NYHA IV | 0 percentage of participants |
Other Pre-specified
NYHA Functional Classification
Proportion of subjects with a NYHA Functional Class of I,II, III or IV (range I-IV where a lower score indicates less limitation in physical activity)
Time frame: One year from index procedure
Population: Analysis population included all subjects in whom a Portico valve implant was attempted (enrolled subjects). Information was not available for one subject.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Portico Valve and FlexNav™ Delivery System | NYHA Functional Classification | NYHA IV | 0.0 percentage of participants |
| Portico Valve and FlexNav™ Delivery System | NYHA Functional Classification | NYHA I | 57.5 percentage of participants |
| Portico Valve and FlexNav™ Delivery System | NYHA Functional Classification | NYHA II | 40.0 percentage of participants |
| Portico Valve and FlexNav™ Delivery System | NYHA Functional Classification | NYHA III | 2.5 percentage of participants |
Other Pre-specified
Severity of Paravalvular Leak
Echocardiographic core-laboratory derived severity of paravalvular leak
Time frame: 30 days from index procedure
Population: Analysis population included all subjects in whom a Portico valve implant was attempted (enrolled subjects) with an analyzable echocardiogram at 30 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Portico Valve and FlexNav™ Delivery System | Severity of Paravalvular Leak | None/Trace/Trivial PVL | 53.5 percentage of patients |
| Portico Valve and FlexNav™ Delivery System | Severity of Paravalvular Leak | Mild PVL | 46.5 percentage of patients |
| Portico Valve and FlexNav™ Delivery System | Severity of Paravalvular Leak | Moderate PVL | 0 percentage of patients |
| Portico Valve and FlexNav™ Delivery System | Severity of Paravalvular Leak | Severe PVL | 0 percentage of patients |
Other Pre-specified
Severity of Paravalvular Leak
Echocardiographic core-laboratory derived severity of paravalvular leak
Time frame: One year from index procedure
Population: Analysis population included all subjects in whom a Portico valve implant was attempted (enrolled subjects) with an analyzable echocardiogram at 30 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Portico Valve and FlexNav™ Delivery System | Severity of Paravalvular Leak | None/Trace/Trivial PVL | 72.2 percentage of patients |
| Portico Valve and FlexNav™ Delivery System | Severity of Paravalvular Leak | Mild PVL | 27.8 percentage of patients |
| Portico Valve and FlexNav™ Delivery System | Severity of Paravalvular Leak | Moderate PVL | 0.0 percentage of patients |
| Portico Valve and FlexNav™ Delivery System | Severity of Paravalvular Leak | Severe PVL | 0.0 percentage of patients |
Other Pre-specified
Technical Device Success
Technical device success defined as successful vascular access, delivery and deployment of the Portico Valve; retrieval with the delivery system and correct positioning of a single valve in the proper anatomical location.
Time frame: Over the duration of index procedure, an average of 60.6 minutes
Population: Analysis population included all subjects in whom a Portico valve implant was attempted (enrolled subjects)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Portico Valve and FlexNav™ Delivery System | Technical Device Success | 100 percentage of participants |