Symptomatic Severe Aortic Stenosis
Conditions
Keywords
Aortic Stenosis, Transcatheter Aortic Valve Implantation, Heart Valve Disease, High Surgical Risk, Portico NG (Navitor) Valve, Extreme Surgical Risk, Navitor Titan Valve
Brief summary
The purpose of this clinical study is to evaluate the acute safety and effectiveness of the next-generation Navitor (Portico™ NG) Transcatheter Aortic Heart Valve as assessed by the rate of all-cause mortality at 30 days and the rate of moderate or greater paravalvular leak at 30 days in a high or extreme surgical risk patient population to support CE (Conformité Européenne) Mark and FDA approval.
Detailed description
The Portico NG Approval study will be conducted as a prospective, multi-center, international, single-arm investigational study. Up to 399 (includes up to 20 roll-ins) 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 Navitor Transcatheter Aortic Heart Valve implantation will undergo Navitor Valve implantation via a transfemoral or alternative access approach according to the site's anesthesia protocol for TAVR (transcatheter aortic valve replacement) procedure. Subjects participating in the clinical study will be followed for a total of 12 months with data collected at screening, baseline, procedure, prior to hospital discharge, and follow-up at 30 days, 12 months and annually through 10 years. This study will also include a product size extension, Navitor Titan™ valve, which includes up to 90 subjects (Titan cohort) who will undergo an implant attempt with the Navitor Titan valve. Subjects enrolled in the Titan cohort will undergo the same screening, baseline, procedure and follow-up assessments as the Portico NG cohort.
Interventions
DEVICEPortico™ NG (Navitor) Valve and FlexNav™ Delivery System
Subjects will undergo transcatheter aortic valve implantation (TAVI) with the new generation Portico NG (Navitor) valve and second-generation FlexNav Delivery system via a transfemoral or alternative access approach according to the site's anesthesia protocol for TAVR procedures.
DEVICENavitor Titan Valve (35mm) Valve and Large FlexNav™ Delivery System
Subjects will undergo transcatheter aortic valve implantation (TAVI) with the Navitor Titan valve and large FlexNav Delivery system via a transfemoral or alternative access approach according to the site's anesthesia protocol for TAVR procedures.
Sponsors
Abbott Medical Devices
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Devices under investigation in this clinical study include the Portico™ (Navitor) Valve (23mm, 25mm, 27mm and 29mm sizes), Navitor Titan Valve (35 mm), FlexNav™ Delivery System (small and large) and Portico™ NG (Navitor) Loading System(s) (small and large), and Navitor Loading System - LG+, all of which are currently approved for investigational use only.
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Subjects must have a Society of Thoracic Surgeons (STS) score of ≥7% OR documented heart team agreement of high or extreme risk for surgical aortic valve replacement due to frailty or co-morbidities not captured by the STS score. 2. Subject has symptomatic aortic stenosis as demonstrated by NYHA (New York Heart Association) Functional Classification of II, III, or IV. 3. Subject has senile degenerative aortic valve stenosis with echo-derived criteria, defined as: aortic valve area (AVA) of ≤ 1.0 cm2 (or indexed EOA (effective orifice area) ≤ 0.6 cm2/m2) AND mean gradient ≥40 mmHg or peak jet velocity ≥ 4.0 m/s or doppler velocity index (DVI) ≤0.25. (Qualifying AVA baseline measurement must be within 90 days prior to informed consent). 4. Aortic annulus diameter of 19-30mm and ascending aorta diameter for the specified valve size listed in the IFU (Instructions For Use), as measured by CT (Computed Tomography) Key
Exclusion criteria
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. Any percutaneous coronary or peripheral interventional procedure performed within 30 days prior to index procedure. 3. Blood dyscrasias as defined: leukopenia (WBC\<3000 mm3), acute anemia (Hb \< 9 g/dL), thrombocytopenia (platelet count \<50,000 cells/mm³). History of bleeding diathesis or coagulopathy 4. Active peptic ulcer or upper GI bleeding within 3 months prior to index procedure that would preclude anticoagulation 5. Recent (within 6 months prior to index procedure date) cerebrovascular accident (CVA) or a transient ischemic attack (TIA). 6. Mixed aortic valve disease (aortic stenosis and aortic regurgitation with predominant aortic regurgitation 3-4+). 7. 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 left ventricular outflow tract (LVOT), severe (greater than or equal to 3+) mitral insufficiency, or severe mitral stenosis with pulmonary compromise. 8. Minimum access vessel diameter of \<5.0mm for small FlexNav™ Delivery System and \<5.5 mm for large FlexNav™ Delivery System
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Safety Endpoint is All-cause Mortality | at 30 days | All-cause mortality is defined as the total number of deaths in each cohort at 30 days. |
| Primary Effectiveness Endpoint is Moderate or Greater Paravalvular Leak | at 30 days | Number of participants with moderate or greater paravalvular leak at 30 days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Non-hierarchical Composite of All-cause Mortality, Disabling Stroke, Life Threatening Bleeding, Acute Kidney Injury (Stage 3), or Major Vascular Complications | at 30 days | The secondary endpoint is defined as a non-hierarchical composite of all-cause mortality, disabling stroke, life threatening bleeding, acute kidney injury (stage 3), or major vascular complications at 30 days. |
Countries
Australia, Denmark, Italy, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Portico™ NG (Navitor) Valve, FlexNav™ Delivery System Portico ™ NG (Navitor) valve implantation with the new generation Portico NG (Navitor) valve (23mm, 25mm, 27mm and 29mm sizes), and the second-generation FlexNav Delivery system (small and large), Portico™ NG (Navitor) Loading System(s) (small and large).
Portico™ NG (Navitor) Valve and FlexNav™ Delivery System: Subjects will undergo transcatheter aortic valve implantation (TAVI) with the new generation Portico NG (Navitor) valve and second-generation FlexNav Delivery system via a transfemoral or alternative access approach according to the site's anesthesia protocol for TAVR procedures. | 260 |
| Navitor Titan Valve Navitor Titan Valve (35mm) implantation with the large FlexNav Delivery system and Navitor Loading System - LG+.
Navitor Titan Valve (35mm) Valve and Large FlexNav™ Delivery System: Subjects will undergo transcatheter aortic valve implantation (TAVI) with the Navitor Titan valve and large FlexNav Delivery system via a transfemoral or alternative access approach according to the site's anesthesia protocol for TAVR procedures. | 73 |
| Total | 333 |
Baseline characteristics
| Characteristic | Portico™ NG (Navitor) Valve, FlexNav™ Delivery System | Navitor Titan Valve | Total |
|---|---|---|---|
| Age, Continuous | 83.4 Years STANDARD_DEVIATION 5.4 | 80.6 Years STANDARD_DEVIATION 5.2 | 82.0 Years STANDARD_DEVIATION 5.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 2 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 257 Participants | 71 Participants | 328 Participants |
| EuroSCORE II | 3.4 Percentage of Risk STANDARD_DEVIATION 2.3 | 2.7 Percentage of Risk STANDARD_DEVIATION 1.7 | 3.05 Percentage of Risk STANDARD_DEVIATION 2 |
| NYHA Class NYHA I | 0 Participants | 0 Participants | 0 Participants |
| NYHA Class NYHA II | 117 Participants | 53 Participants | 170 Participants |
| NYHA Class NYHA III | 138 Participants | 19 Participants | 157 Participants |
| NYHA Class NYHA IV | 5 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 1 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 64 Participants | 16 Participants | 80 Participants |
| Race (NIH/OMB) White | 189 Participants | 56 Participants | 245 Participants |
| Sex: Female, Male Female | 149 Participants | 1 Participants | 150 Participants |
| Sex: Female, Male Male | 111 Participants | 72 Participants | 183 Participants |
| STS Risk of Mortality | 3.9 Percentage of Risk STANDARD_DEVIATION 2.1 | 2.7 Percentage of Risk STANDARD_DEVIATION 1.3 | 3.3 Percentage of Risk STANDARD_DEVIATION 1.7 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 44 / 260 | 6 / 73 |
| other Total, other adverse events | 197 / 260 | 54 / 73 |
| serious Total, serious adverse events | 180 / 260 | 50 / 73 |
Outcome results
Primary
Primary Effectiveness Endpoint is Moderate or Greater Paravalvular Leak
Number of participants with moderate or greater paravalvular leak at 30 days.
Time frame: at 30 days
Population: All available subjects with echocardiographic data have been analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Portico™ NG (Navitor) Valve, FlexNav™ Delivery System | Primary Effectiveness Endpoint is Moderate or Greater Paravalvular Leak | None/Trace PVL | 198 Participants |
| Portico™ NG (Navitor) Valve, FlexNav™ Delivery System | Primary Effectiveness Endpoint is Moderate or Greater Paravalvular Leak | Mild PVL | 50 Participants |
| Portico™ NG (Navitor) Valve, FlexNav™ Delivery System | Primary Effectiveness Endpoint is Moderate or Greater Paravalvular Leak | Moderate PVL | 0 Participants |
| Portico™ NG (Navitor) Valve, FlexNav™ Delivery System | Primary Effectiveness Endpoint is Moderate or Greater Paravalvular Leak | Severe PVL | 0 Participants |
| Navitor Titan Valve | Primary Effectiveness Endpoint is Moderate or Greater Paravalvular Leak | Severe PVL | 0 Participants |
| Navitor Titan Valve | Primary Effectiveness Endpoint is Moderate or Greater Paravalvular Leak | None/Trace PVL | 61 Participants |
| Navitor Titan Valve | Primary Effectiveness Endpoint is Moderate or Greater Paravalvular Leak | Moderate PVL | 0 Participants |
| Navitor Titan Valve | Primary Effectiveness Endpoint is Moderate or Greater Paravalvular Leak | Mild PVL | 7 Participants |
Primary
Primary Safety Endpoint is All-cause Mortality
All-cause mortality is defined as the total number of deaths in each cohort at 30 days.
Time frame: at 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Portico™ NG (Navitor) Valve, FlexNav™ Delivery System | Primary Safety Endpoint is All-cause Mortality | 5 Participants |
| Navitor Titan Valve | Primary Safety Endpoint is All-cause Mortality | 1 Participants |
Secondary
Non-hierarchical Composite of All-cause Mortality, Disabling Stroke, Life Threatening Bleeding, Acute Kidney Injury (Stage 3), or Major Vascular Complications
The secondary endpoint is defined as a non-hierarchical composite of all-cause mortality, disabling stroke, life threatening bleeding, acute kidney injury (stage 3), or major vascular complications at 30 days.
Time frame: at 30 days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Portico™ NG (Navitor) Valve, FlexNav™ Delivery System | Non-hierarchical Composite of All-cause Mortality, Disabling Stroke, Life Threatening Bleeding, Acute Kidney Injury (Stage 3), or Major Vascular Complications | Myocardial Infarction | 2 Participants |
| Portico™ NG (Navitor) Valve, FlexNav™ Delivery System | Non-hierarchical Composite of All-cause Mortality, Disabling Stroke, Life Threatening Bleeding, Acute Kidney Injury (Stage 3), or Major Vascular Complications | Major Bleeding | 12 Participants |
| Portico™ NG (Navitor) Valve, FlexNav™ Delivery System | Non-hierarchical Composite of All-cause Mortality, Disabling Stroke, Life Threatening Bleeding, Acute Kidney Injury (Stage 3), or Major Vascular Complications | Transient Ischemic Attack | 2 Participants |
| Portico™ NG (Navitor) Valve, FlexNav™ Delivery System | Non-hierarchical Composite of All-cause Mortality, Disabling Stroke, Life Threatening Bleeding, Acute Kidney Injury (Stage 3), or Major Vascular Complications | Major Vascular Complications | 11 Participants |
| Portico™ NG (Navitor) Valve, FlexNav™ Delivery System | Non-hierarchical Composite of All-cause Mortality, Disabling Stroke, Life Threatening Bleeding, Acute Kidney Injury (Stage 3), or Major Vascular Complications | All Stroke | 10 Participants |
| Portico™ NG (Navitor) Valve, FlexNav™ Delivery System | Non-hierarchical Composite of All-cause Mortality, Disabling Stroke, Life Threatening Bleeding, Acute Kidney Injury (Stage 3), or Major Vascular Complications | Acute Kidney Injury | 5 Participants |
| Portico™ NG (Navitor) Valve, FlexNav™ Delivery System | Non-hierarchical Composite of All-cause Mortality, Disabling Stroke, Life Threatening Bleeding, Acute Kidney Injury (Stage 3), or Major Vascular Complications | Life-Threatening Bleeding | 10 Participants |
| Portico™ NG (Navitor) Valve, FlexNav™ Delivery System | Non-hierarchical Composite of All-cause Mortality, Disabling Stroke, Life Threatening Bleeding, Acute Kidney Injury (Stage 3), or Major Vascular Complications | Valve Thrombosis | 0 Participants |
| Portico™ NG (Navitor) Valve, FlexNav™ Delivery System | Non-hierarchical Composite of All-cause Mortality, Disabling Stroke, Life Threatening Bleeding, Acute Kidney Injury (Stage 3), or Major Vascular Complications | All-Cause Mortality | 5 Participants |
| Navitor Titan Valve | Non-hierarchical Composite of All-cause Mortality, Disabling Stroke, Life Threatening Bleeding, Acute Kidney Injury (Stage 3), or Major Vascular Complications | Valve Thrombosis | 0 Participants |
| Navitor Titan Valve | Non-hierarchical Composite of All-cause Mortality, Disabling Stroke, Life Threatening Bleeding, Acute Kidney Injury (Stage 3), or Major Vascular Complications | All-Cause Mortality | 1 Participants |
| Navitor Titan Valve | Non-hierarchical Composite of All-cause Mortality, Disabling Stroke, Life Threatening Bleeding, Acute Kidney Injury (Stage 3), or Major Vascular Complications | Myocardial Infarction | 1 Participants |
| Navitor Titan Valve | Non-hierarchical Composite of All-cause Mortality, Disabling Stroke, Life Threatening Bleeding, Acute Kidney Injury (Stage 3), or Major Vascular Complications | All Stroke | 2 Participants |
| Navitor Titan Valve | Non-hierarchical Composite of All-cause Mortality, Disabling Stroke, Life Threatening Bleeding, Acute Kidney Injury (Stage 3), or Major Vascular Complications | Transient Ischemic Attack | 2 Participants |
| Navitor Titan Valve | Non-hierarchical Composite of All-cause Mortality, Disabling Stroke, Life Threatening Bleeding, Acute Kidney Injury (Stage 3), or Major Vascular Complications | Life-Threatening Bleeding | 0 Participants |
| Navitor Titan Valve | Non-hierarchical Composite of All-cause Mortality, Disabling Stroke, Life Threatening Bleeding, Acute Kidney Injury (Stage 3), or Major Vascular Complications | Major Bleeding | 2 Participants |
| Navitor Titan Valve | Non-hierarchical Composite of All-cause Mortality, Disabling Stroke, Life Threatening Bleeding, Acute Kidney Injury (Stage 3), or Major Vascular Complications | Major Vascular Complications | 3 Participants |
| Navitor Titan Valve | Non-hierarchical Composite of All-cause Mortality, Disabling Stroke, Life Threatening Bleeding, Acute Kidney Injury (Stage 3), or Major Vascular Complications | Acute Kidney Injury | 0 Participants |