Clinical trial NCT02000115: Portico Re-sheathable Transcatheter Aortic Valve System US IDE Trial
Official title: Portico Re-sheathable Transcatheter Aortic Valve System US IDE Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Aortic Valve Stenosis
Keywords: Portico
Lead sponsor: Abbott Medical Devices
Sponsor class: INDUSTRY
First posted: 2013-12-03
Enrollment: 1242
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 Exclusion Criteria (Transcatheter Access Related)

For selection of an appropriate alternative access delivery method, subjects were screened using the following access specific exclusion criteria:

Transaortic (TAo) Subject Cohort Specific Exclusion Criteria

1. Subject has pre-existing patent RIMA graft that would preclude access.
2. Subject has a hostile chest or other condition that complicates transaortic access.
3. Subject has a porcelain aorta, defined as an extensive circumferential calcification of the ascending aorta that would complicate TAo access.

Additional exclusion criteria for transaortic access using the FlexNav™ Delivery System:

1. Subject has a distance between the annular plane and the aortic access site \<7 cm (2.8")
2. Subject has a distance between the annular plane and the separate introducer sheath distal tip \<6 cm (2.4")

Subclavian/Axillary Subject Cohort Specific Exclusion Criteria

1. Subject's access vessel (subclavian/axillary) diameter will not allow for introduction of the applicable 18 Fr or 19 Fr delivery system.
2. Subject's subclavian/axillary arteries have severe calcification and/or tortuosity.
3. Subject's aortic root angulation is:

   * Left Subclavian/Left Axillary: \>70◦
   * Right Subclavian/Right Axillary: \>30◦
4. Subject has a history of patent LIMA/RIMA graft that would preclude access

Additional exclusion criteria for subclavian/axillary access using the FlexNav™ Delivery System:

1. Subject's access vessel (subclavian/axillary) has a distance between the annular plane and the integrated sheath distal tip \<17 cm (6.7")
2. Subject's access vessel requires the delivery system to be advanced through a separate introducer sheath

Primary outcomes:
measure: Primary Effectiveness Endpoint (Randomized IDE Cohort)
timeFrame: One-year from randomization
measure: Primary Safety Endpoint (Randomized IDE Cohort)
timeFrame: 30 days from randomization
measure: Percentage of Patients With Major Vascular Complications (Primary Safety Endpoint- FlexNav Delivery System Study)
timeFrame: 30 days from index procedure
Secondary outcomes:
measure: Percentage of Patients With Severe Aortic Regurgitation (Randomized IDE Cohort)
timeFrame: One year
measure: Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score (Randomized IDE Cohort)
timeFrame: One year
measure: Percentage of Patients With Moderate or Severe Aortic Regurgitation (Randomized IDE Cohort)
timeFrame: One year
measure: Six-Minute Walk Test- Total Distance Walked (Randomized IDE Cohort)
timeFrame: One year
measure: Percentage of Patients With Composite Safety Endpoint (Nested Valve-in-Valve Registry)
timeFrame: 30 days from index procedure
measure: Percentage of Patients With All-cause Mortality or Disabling Stroke (Nested Valve-in-Valve Registry)
timeFrame: One year from index procedure
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University Hospital - Univ. of Alabama at Birmingham (UAB)
state: Alabama
city: Phoenix
country: United States
facility: Banner - University Medical Center Phoenix
state: Arizona
city: Concord
country: United States
facility: John Muir Medical Center
state: California
city: La Jolla
country: United States
facility: Scripps Green Hospital
state: California
city: Los Angeles
country: United States
facility: USC University Hospital
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian
state: California
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: Pasadena
country: United States
facility: Huntington Memorial Hospital
state: California
city: Sacramento
country: United States
facility: Sutter Memorial Hospital
state: California
city: Sacramento
country: United States
facility: Mercy General Hospital
state: California
city: Thousand Oaks
country: United States
facility: Los Robles Regional Medical Center
state: California
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Atlantis
country: United States
facility: JFK Medical Center
state: Florida
city: Clearwater
country: United States
facility: Morton Plant Valve Clinic
state: Florida
city: Delray Beach
country: United States
facility: Delray Medical Center
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Orlando
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Oak Lawn
country: United States
facility: Advocate Christ Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: St. Vincent Hospital
state: Indiana
city: West Des Moines
country: United States
facility: Iowa Heart Center
state: Iowa
city: Wichita
country: United States
facility: Cardiovascular Research Institute of Kansas
state: Kansas
city: New Orleans
country: United States
facility: Ochsner Medical Center
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Lansing
country: United States
facility: Sparrow Clinical Research Institute
state: Michigan
city: Minneapolis
country: United States
facility: Abbott Northwestern Hospital
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Tupelo
country: United States
facility: North Mississippi Medical Center
state: Mississippi
city: Kansas City
country: United States
facility: St. Luke's Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Springfield
country: United States
facility: Mercy Hospital Springfield
state: Missouri
city: Manchester
country: United States
facility: Catholic Medical Center
state: New Hampshire
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: Brooklyn
country: United States
facility: Maimonides Medical Center
state: New York
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital / Cornell University
state: New York
city: New York
country: United States
facility: Lenox Hill Hospital
state: New York
city: Roslyn
country: United States
facility: St. Francis Hospital
state: New York
city: Asheville
country: United States
facility: Mission Health and Hospitals
state: North Carolina
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Greenville
country: United States
facility: East Carolina Heart Institute
state: North Carolina
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Heart Hospital
state: Oklahoma
city: Harrisburg
country: United States
facility: Pinnacle Health System
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny Singer Research Institute
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Wynnewood
country: United States
facility: Main Line Health Center/Lankenau Hospital
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Sanford USD Medical Center
state: South Dakota
city: Memphis
country: United States
facility: Baptist Memorial Hospital
state: Tennessee
city: Nashville
country: United States
facility: Centennial Medical Center
state: Tennessee
city: Austin
country: United States
facility: Heart Hospital of Austin
state: Texas
city: Houston
country: United States
facility: CHI St. Luke's Health Baylor College of Medicine Medical Center
state: Texas
city: Houston
country: United States
facility: Memorial Hermann Hospital
state: Texas
city: Houston
country: United States
facility: The Methodist Hospital
state: Texas
city: Plano
country: United States
facility: The Heart Hospital Baylor Plano
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Hospital
state: Utah
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Norfolk
country: United States
facility: Sentara Norfolk General Hospital
state: Virginia
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Sydney
country: Australia
facility: Macquarie University Hospital
state: New South Wales
city: Chermside
country: Australia
facility: The Prince Charles Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
Study officials:
affiliation: Cedars-Sinai Medical Center
name: Raj R Makkar, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Los Robles Regional Medical Center
name: Gregory P Fontana, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Makkar RR, Cheng W, Waksman R, Satler LF, Chakravarty T, Groh M, Abernethy W, Russo MJ, Heimansohn D, Hermiller J, Worthley S, Chehab B, Cunningham M, Matthews R, Ramana RK, Yong G, Ruiz CE, Chen C, Asch FM, Nakamura M, Jilaihawi H, Sharma R, Yoon SH, Pichard AD, Kapadia S, Reardon MJ, Bhatt DL, Fontana GP. Self-expanding intra-annular versus commercially available transcatheter heart valves in high and extreme risk patients with severe aortic stenosis (PORTICO IDE): a randomised, controlled, non-inferiority trial. Lancet. 2020 Sep 5;396(10252):669-683. doi: 10.1016/S0140-6736(20)31358-1. Epub 2020 Jun 25.
citation: Makkar RR, Fontana G, Jilaihawi H, Chakravarty T, Kofoed KF, De Backer O, Asch FM, Ruiz CE, Olsen NT, Trento A, Friedman J, Berman D, Cheng W, Kashif M, Jelnin V, Kliger CA, Guo H, Pichard AD, Weissman NJ, Kapadia S, Manasse E, Bhatt DL, Leon MB, Sondergaard L. Possible Subclinical Leaflet Thrombosis in Bioprosthetic Aortic Valves. N Engl J Med. 2015 Nov 19;373(21):2015-24. doi: 10.1056/NEJMoa1509233. Epub 2015 Oct 5.