Aortic Valve Stenosis
Conditions
Keywords
Portico
Brief summary
The objective of the PORTICO pivotal IDE trial is to evaluate the safety and effectiveness of the St Jude Medical (SJM) Portico Transcatheter Heart Valve and Delivery Systems (Portico) in the treatment of severe symptomatic aortic stenosis via transfemoral and alternative delivery methods in high risk and extreme risk patients.
Detailed description
The PORTICO pivotal IDE trial will include a randomized cohort of 750 subjects enrolled at up to 70 investigational sites in the United States and Australia. Patients will be randomized (1:1) to receive the SJM Portico Transcatheter Heart Valve and Delivery Systems (Portico) or any FDA-approved, commercially-available Transcatheter Aortic Valve Replacement (TAVR) System. The randomized cohort will be tested for two co-primary endpoints at 30 days (primary safety endpoint) and 1 year (primary effectiveness endpoint). At the time of the primary randomized cohort analysis, the risk cohorts will be combined and analysis will be conducted on the intention-to-treat (n=750) population. The FlexNav Delivery System study will be conducted as a separate arm of the PORTICO IDE trial and will include up to 200 high or extreme risk subjects; including a minimum of 100 analysis subjects. The study will characterize the safety of the next-generation Portico Delivery System (FlexNav™ Delivery System). The primary analysis cohort will include FlexNav analysis subjects. The IDE Valve-in-Valve registry will enroll up to 100 high or extreme risk subjects with a failed surgical bioprosthesis who are eligible to receive a Portico Transcatheter Heart Valve. All subjects enrolled in the PORTICO pivotal IDE trial will undergo follow-up at baseline, peri- and post-procedure, at discharge or 7 days post-procedure (whichever comes first), 30 days, 6 months, 12-months and then annually through 5-years.
Interventions
St. Jude Medical transcatheter Portico aortic valve
DEVICECommercially available transcatheter aortic valve
Commercially available transcatheter aortic valve
Sponsors
Abbott Medical Devices
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subjects must have co-morbidities such that the surgeon and cardiologist Co-Investigators concur that the predicted risk of operative mortality is ≥15% or a minimum Society of Thoracic Surgeons (STS) score of 8%. A candidate who does not meet the STS score criteria of ≥ 8% can be included in the study if a peer review by at least two surgeons concludes and documents that the patient's predicted risk of operative mortality is ≥15%. The surgeon's assessment of operative comorbidities 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 21 years of age or older at the time of consent. 3. Subject has senile degenerative aortic valve stenosis with echocardiographically derived criteria: mean gradient \>40 mmHg or jet velocity greater than 4.0 m/s or Doppler Velocity Index \<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 New York Heart Association (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 computerized tomography (CT) conducted within 12 months prior to informed consent. Note: if CT is 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 if approved by the subject selection committee. For a subject to be considered an Extreme Risk candidate they must meet # 2, 3, 4, 5, 6, 7 of the above criteria, and 8. The subject, after formal consults by a cardiologist and two cardiovascular surgeons agree that medical factors preclude 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 surgeons' 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
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 non-calcified 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 left ventricular outflow tract (LVOT), severe (greater than 3+) mitral insufficiency, or severe mitral stenosis with pulmonary compromise. Subjects with pre-existing surgical bioprosthetic aortic heart valve should be considered for the Valve-in-Valve registry. 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 gastrointestinal (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 non-cardiac 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 (applicable for transfemoral patients only). 21. Native aortic annulus size \< 19 mm or \> 27 mm per the baseline diagnostic imaging. 22. Aortic root angulation \> 70° (applicable for transfemoral patients only). 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 placement of the introducer sheath such as severe obstructive calcification, or severe tortuosity (applicable for transfemoral patients only). Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Effectiveness Endpoint (Randomized IDE Cohort) | One-year from randomization | A composite of all-cause mortality or disabling stroke at one year. |
| Primary Safety Endpoint (Randomized IDE Cohort) | 30 days from randomization | Non-hierarchical composite of all-cause mortality, disabling stroke, life threatening bleeding requiring blood transfusion, acute kidney injury requiring dialysis, or major vascular complications at 30 days. |
| Percentage of Patients With Major Vascular Complications (Primary Safety Endpoint- FlexNav Delivery System Study) | 30 days from index procedure | Valve Academic Research Consortium (VARC) 2- defined major vascular complications |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Six-Minute Walk Test- Total Distance Walked (Randomized IDE Cohort) | One year | Six-minute walk distance at one year |
| Percentage of Patients With Severe Aortic Regurgitation (Randomized IDE Cohort) | One year | Severe aortic regurgitation (AR) at one year |
| Percentage of Patients With All-cause Mortality or Disabling Stroke (Nested Valve-in-Valve Registry) | One year from index procedure | A composite of all-cause mortality or disabling stroke at one year Anticipated completion data (2023) |
| Percentage of Patients With Composite Safety Endpoint (Nested Valve-in-Valve Registry) | 30 days from index procedure | Non-hierarchical composite of all-cause mortality, disabling stroke, life threatening bleeding requiring blood transfusion, acute kidney injury requiring dialysis, or major vascular complications at 30 days from index procedure. Anticipated completion date (2022) |
| Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score (Randomized IDE Cohort) | One year | Kansas City Cardiomyopathy Questionnaire (KCCQ) at one year. Scale 0 to 100; with higher scores indicating better symptoms and physical functioning |
| Percentage of Patients With Moderate or Severe Aortic Regurgitation (Randomized IDE Cohort) | One year | Moderate or severe aortic regurgitation at one year |
Countries
Australia, United States
Participant flow
Recruitment details
750 subjects were randomized (1:1) to the Portico valve (n=381) and CAV (n=369) groups. 100 analysis subjects were enrolled in the FlexNav Delivery System study. 53 subjects are currently enrolled in the IDE Valve-in-Valve registry ( enrollment ongoing)
Pre-assignment details
Only the Randomized IDE cohort (N=750) and FlexNav Delivery System Study (N=100 analysis) that completed subject enrollment and reached their pre-defined primary endpoint(s) are included in the Results Section. The IDE Valve-in-Valve registry is still enrolling subjects. A total of 53 out of a required 100 subjects have been enrolled to date.
Participants by arm
| Arm | Count |
|---|---|
| Randomized IDE Cohort, Portico Valve Portico transcatheter aortic valve and Portico delivery system | 381 |
| Randomized IDE Cohort, CAV Any FDA approved, commercially-available transcatheter aortic valve (CAV). | 369 |
| FlexNav Delivery System Study Portico transcatheter aortic valve and FlexNav delivery system | 100 |
| Total | 850 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 56 | 45 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Overall Study | Missed Visit | 6 | 8 | 1 | 0 |
| Overall Study | Non-compliance | 2 | 1 | 0 | 0 |
| Overall Study | Physician Decision | 2 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 2 | 1 | 0 | 0 |
| Overall Study | Still on Study | 0 | 0 | 0 | 53 |
| Overall Study | Withdrawal by Subject | 11 | 11 | 0 | 0 |
| Overall Study | Withdrawn on day of randomization | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Randomized IDE Cohort, Portico Valve | Total | FlexNav Delivery System Study | Randomized IDE Cohort, CAV |
|---|---|---|---|---|
| Age, Continuous | 83.0 years STANDARD_DEVIATION 7.6 | 83.5 years STANDARD_DEVIATION 7.2 | 85.1 years STANDARD_DEVIATION 5.8 | 83.7 years STANDARD_DEVIATION 7 |
| Race/Ethnicity, Customized Race American Indian or Alaska native | 1 Participants | 2 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 4 Participants | 7 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Black or African American | 14 Participants | 38 Participants | 7 Participants | 17 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or other Pacific Islander | 1 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Other | 7 Participants | 16 Participants | 0 Participants | 9 Participants |
| Race/Ethnicity, Customized Race White | 354 Participants | 785 Participants | 92 Participants | 339 Participants |
| Region of Enrollment Australia | 30 participants | 88 participants | 25 participants | 29 participants |
| Region of Enrollment United States | 351 participants | 796 participants | 75 participants | 340 participants |
| Sex: Female, Male Female | 198 Participants | 452 Participants | 57 Participants | 197 Participants |
| Sex: Female, Male Male | 183 Participants | 398 Participants | 43 Participants | 172 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 56 / 381 | 45 / 369 | 0 / 100 |
| other Total, other adverse events | 298 / 381 | 269 / 369 | 54 / 100 |
| serious Total, serious adverse events | 273 / 381 | 231 / 369 | 44 / 100 |
Outcome results
Primary
Percentage of Patients With Major Vascular Complications (Primary Safety Endpoint- FlexNav Delivery System Study)
Valve Academic Research Consortium (VARC) 2- defined major vascular complications
Time frame: 30 days from index procedure
Population: All enrolled analysis subjects
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized IDE Cohort, Portico Valve | Percentage of Patients With Major Vascular Complications (Primary Safety Endpoint- FlexNav Delivery System Study) | 6.0 percentage of participants |
Primary
Primary Effectiveness Endpoint (Randomized IDE Cohort)
A composite of all-cause mortality or disabling stroke at one year.
Time frame: One-year from randomization
Population: Intention-to-treat analysis population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Randomized IDE Cohort, Portico Valve | Primary Effectiveness Endpoint (Randomized IDE Cohort) | 14.8 percentage of participants | Standard Error 1.8 |
| Randomized IDE Cohort, CAV | Primary Effectiveness Endpoint (Randomized IDE Cohort) | 13.4 percentage of participants | Standard Error 1.8 |
Comparison: We analysed the primary effectiveness endpoint in the intention-to- treat (ITT) population using the Kaplan-Meier method to estimate event rates, the Greenwood method to calculate the standard error of the Kaplan-Meier estimates, and assuming an asymptotic normal distribution for event rate estimates.p-value: 0.006Kaplan-Meier estimates
Primary
Primary Safety Endpoint (Randomized IDE Cohort)
Non-hierarchical composite of all-cause mortality, disabling stroke, life threatening bleeding requiring blood transfusion, acute kidney injury requiring dialysis, or major vascular complications at 30 days.
Time frame: 30 days from randomization
Population: Intention-to-treat analysis population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Randomized IDE Cohort, Portico Valve | Primary Safety Endpoint (Randomized IDE Cohort) | 13.8 percentage of participants | Standard Deviation 1.8 |
| Randomized IDE Cohort, CAV | Primary Safety Endpoint (Randomized IDE Cohort) | 9.6 percentage of participants | Standard Deviation 1.5 |
Comparison: We analysed the primary safety endpoint in the intention-to-treat (ITT) population using the Kaplan-Meier method to estimate event rates, the Greenwood method to calculate the standard error of the Kaplan-Meier estimates, and assuming an asymptotic normal distribution for event rate estimates.p-value: 0.03Kaplan-Meier estimates
Secondary
Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score (Randomized IDE Cohort)
Kansas City Cardiomyopathy Questionnaire (KCCQ) at one year. Scale 0 to 100; with higher scores indicating better symptoms and physical functioning
Time frame: One year
Population: All randomized subjects with available data at one-year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Randomized IDE Cohort, Portico Valve | Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score (Randomized IDE Cohort) | 75.4 units on a scale | Standard Deviation 22.2 |
| Randomized IDE Cohort, CAV | Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score (Randomized IDE Cohort) | 75.9 units on a scale | Standard Deviation 20.5 |
p-value: <0.0001two-sample t-test
Secondary
Percentage of Patients With All-cause Mortality or Disabling Stroke (Nested Valve-in-Valve Registry)
A composite of all-cause mortality or disabling stroke at one year Anticipated completion data (2023)
Time frame: One year from index procedure
Secondary
Percentage of Patients With Composite Safety Endpoint (Nested Valve-in-Valve Registry)
Non-hierarchical composite of all-cause mortality, disabling stroke, life threatening bleeding requiring blood transfusion, acute kidney injury requiring dialysis, or major vascular complications at 30 days from index procedure. Anticipated completion date (2022)
Time frame: 30 days from index procedure
Secondary
Percentage of Patients With Moderate or Severe Aortic Regurgitation (Randomized IDE Cohort)
Moderate or severe aortic regurgitation at one year
Time frame: One year
Population: All randomized subjects with available data at one-year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized IDE Cohort, Portico Valve | Percentage of Patients With Moderate or Severe Aortic Regurgitation (Randomized IDE Cohort) | 7.1 percentage of participants |
| Randomized IDE Cohort, CAV | Percentage of Patients With Moderate or Severe Aortic Regurgitation (Randomized IDE Cohort) | 1.5 percentage of participants |
p-value: 0.4Farrington-Manning test
Secondary
Percentage of Patients With Severe Aortic Regurgitation (Randomized IDE Cohort)
Severe aortic regurgitation (AR) at one year
Time frame: One year
Population: All randomized subjects with available data at one-year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized IDE Cohort, Portico Valve | Percentage of Patients With Severe Aortic Regurgitation (Randomized IDE Cohort) | 0.4 percentage of participants |
| Randomized IDE Cohort, CAV | Percentage of Patients With Severe Aortic Regurgitation (Randomized IDE Cohort) | 0 percentage of participants |
p-value: 0.001Farrington-Manning test
Secondary
Six-Minute Walk Test- Total Distance Walked (Randomized IDE Cohort)
Six-minute walk distance at one year
Time frame: One year
Population: All randomized subjects with available data at one-year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Randomized IDE Cohort, Portico Valve | Six-Minute Walk Test- Total Distance Walked (Randomized IDE Cohort) | 235.0 meters | Standard Deviation 125 |
| Randomized IDE Cohort, CAV | Six-Minute Walk Test- Total Distance Walked (Randomized IDE Cohort) | 231.5 meters | Standard Deviation 118.5 |
p-value: 0.0003two sample t-test