A Randomized Evaluation of the SAPIEN XT Transcatheter Valve System in Patients with Aortic Stenosis Who Are Not Candidates for Surgery: PARTNER II, Inoperable Cohort Martin B. Leon, MD on behalf of The PARTNER Trial Investigators ACC 2013 | San Francisco | March 10, 2013
Disclosure Statement of Financial Interest Martin B. Leon, MD Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. Affiliation/Financial Relationship Company • • Abbott, Boston Scientific, Edwards Grant/Research Support Lifesciences, Medtronic • None • C onsulting Fees/Honoraria • Sadra, Claret, Valve Medical, Apica • Major Stock Shareholder/Equity
Background (1) • In the PARTNER I randomized trials, patients with symptomatic severe aortic stenosis, treated using the balloon-expandable SAPIEN transcatheter heart valve system, had reduced mortality compared with standard therapy in patients who could not undergo surgery (“inoperable”) and had similar mortality compared to surgical AVR in patients who were at high-risk for surgery.
Background (2) • However, SAPIEN was associated with peri-procedural complications, including strokes, vascular events, and paravalvular regurgitation. • The new lower-profile SAPIEN XT, currently in general clinical use around the world, incorporates important enhancements to the valve support frame, the valve leaflet geometry, and the delivery system which may be associated with improved clinical outcomes.
Purpose of PARTNER II Inoperable Cohort • To compare the safety and effectiveness of the new SAPIEN XT versus the FDA-approved SAPIEN in a randomized controlled trial for patients with symptomatic severe aortic stenosis who cannot have surgery (“inoperable”). • To apply rigorous clinical trial methodologies including systematic serial neurologic assessments and VARC 2 definitions* for clinical outcomes. * Kappetein AP, et al. J Am Coll Cardiol 2012;60:1438-54
The PARTNER II Inoperable Cohort Study Design Symptomatic Severe Aortic Stenosis ASSESSMENT by Heart Valve Team Inoperable ASSESSMENT: Transfemoral Access n = 560 1:1 Randomization Randomized Patients TF TAVR TF TAVR VS SAPIEN XT SAPIEN Primary Endpoint: All-Cause Mortality + Disabling Stroke + Repeat Hospitalization at One Year (Non-inferiority)
The PARTNER II Trial Study Design Symptomatic Severe Aortic Stenosis ASSESSMENT by Heart Valve Team n = 2000 n = 560 Two Parallel Operable Randomized Inoperable Randomized Randomized Trials (STS ≥4) Patients Patients +6 Nested Registries ASSESSMENT: ASSESSMENT: Yes No Transfemoral Transfemoral Access Access Transapical (TA) / Transfemoral (TF) Yes TransAortic (TAo) 6 Nested Sample 1:1 Randomization 1:1 Randomization 1:1 Randomization Registries Size NR1 (Sm Vessel) 100 NR2 (Transapical) 100 TAVR: TF TAVR Surgical Surgical TF TAVR TF TAVR TA / TAo NR3 (ViV) 100 SAPIEN XT AVR AVR SAPIEN XT SAPIEN SAPIEN XT VS VS VS NR4 (TAo) 100 Primary Endpoint: All-Cause Primary Endpoint: All-Cause Mortality + Mortality + Disabling Stroke + NR5 (29 mm TF) 50 Disabling Stroke at Two Years Repeat Hospitalization at One Year (Non-inferiority) (Non-inferiority) NR6 (29 mm TA) 50
Primary Endpoint • A non-hierarchical composite of all-cause mortality, disabling stroke*, and re-hospitalization for symptoms of aortic stenosis and/or complications of the valve procedure. • Intention-to-treat population, all patients followed for at least one year, non-inferiority trial arm comparison. * Disabling stroke = CEC adjudicated stroke event by a neurologist with a modified Rankin score of 2 or greater at 90-day evaluation
Other Important Endpoints VARC 2 Definitions SAFETY EFFICACY • Cardiovascular mortality • NYHA class • QOL instruments • Major vascular complications • All strokes and TIAs • 6-minute walk test • Peri-procedural Mis • Days alive out-of-hospital • ICU and index hospital LOS • Acute kidney injury • Life-threatening or disabling bleeding ECHO VALVE • No. of transfusions PERFORMANCE • New permanent pacemakers • Mean and peak AV gradient • New onset atrial fibrillation • Effective orifice area (and index) • ≥ 2 THV implants • LV function (ejection fraction) • Repeat intervention • Paravalvular and total AR • Endocarditis • Structural valve deterioration
Inclusion Criteria • Severe AS: Echo-derived AVA < 0.8 cm 2 ( or AVA index < 0.5 cm 2 /m 2 ) and mean AVG > 40 mm Hg or peak jet velocity > 4.0 m/s • Cardiac Symptoms: NYHA Functional Class ≥ II • “Inoperable”: Risk of death or serious irreversible morbidity as assessed by a cardiologist and two surgeons must exceed 50%
Key Exclusion Criteria Anatomic: • Aortic annulus diameter (echo measurement) < 18 mm or > 25 mm • Iliac-femoral anatomy precluding safe sheath insertion (vessel size ≥7 mm diameter) • Severe LV dysfunction (LVEF < 20%) • Untreated CAD requiring revasculariza tion Clinical: • Serum Cr > 3.0 mg/dL or dialysis dependent • Acute MI within 1 month • CVA or TIA within 6 months • Hemodynamic instability
Edwards SAPIEN vs SAPIEN XT Transcatheter Heart Valves SAPIEN THV SAPIEN XT THV NEW FRAME GEOMETRY Cobalt-chromium Stainless Steel • Less metal content • Lower crimp profile NEW FRAME MATERIAL • Cobalt-chromium • Greater tensile and yield strength NEW LEAFLET GEOMETRY • Partially closed RetroFlex 3 NovaFlex
Sheath Size Comparison Minimum Valve Sheath Sheath Valve Vessel Size ID OD Diameter 25F 23mm 22F 7.0mm SAPIEN THV (8.4mm) 22F 23mm 18F 6.0mm SAPIEN XT THV (7.2mm) 28F 26mm 24F 8.0mm SAPIEN THV (9.2mm) 23F 26mm 19F 6.5mm SAPIEN XT THV (7.5mm) 33% reduction in CSA
The PARTNER II Inoperable Cohort Participating Sites Univ. of Washington MN Heart Institute Seattle, WA Minneapolis, MN William Beaumont Hospital Mayo Clinic Royal Oak, MI Rochester, MN Brigham Women’s Hospital Mass. General Hospital Northwestern Univ. Rush Univ . Boston, MA Chicago, IL Boston, MA Chicago, IL The Christ Hospital Columbia University Intermountain Cincinnati, OH NorthShore Univ. New York, NY Medical Center Evanston, IL Cornell University Murray, UT Stanford New York, NY Cleveland Clinic St. Luke’s Hospital University Cleveland, OH Univ. of Pennsylvania Palo Alto, CA Kansas City, MO Philadelphia, PA Barnes-Jewish Hospital Saint Louis, MO Cedars-Sinai Univ. of Virginia Washington Hospital Center OK Cardiology Medical Center Charlottesville, VA Washington, DC Research Group Los Angeles, CA Oklahoma City, OK Scripps Green Hospital Emory University La Jolla, CA Atlanta, GA Medical City Dallas Ochsner Foundation Dallas, TX New Orleans, LA Univ. of TX, Houston Houston, TX 560 Patients Enrolled at Univ. of Miami Miami, FL 28 US Participating Sites
PARTNER II Inoperable Cohort Enrollment by Site (1 of 2) Cedars-Sinai Medical Ctr. Intermountain Medical Ctr. 87 18 Los Angeles, CA Murray, UT Wen Cheng & Raj Makkar Kent Jones & Brian Whisenant Columbia University Ochsner Hospital 75 17 New York, NY New Orleans, LA Susheel Kodali & Mathew Williams Stephen Ramee & Patrick Parrino Emory University Barnes-Jewish Hospital 58 16 Atlanta, GA Saint Louis, MO Vasilis Babaliaros & Vinod Thourani Hersh Maniar, Jr. & Alan Zajarias University of Pennsylvania The Christ Hospital 56 15 Philadelphia, PA Cincinnati, OH Joseph Bavaria & Howard Herrmann Tom Ivey & Dean Kereiakes Washington Hospital Ctr. Cornell University 37 13 Washington, DC New York, NY Paul Corso & Augusto Pichard Karl Krieger & Chiu Wong Medical City Dallas Stanford University 33 12 Dallas, TX Palo Alto, CA David Brown & Todd Dewey Craig Miller & Alan Yeung Cleveland Clinic Mayo Clinic 25 10 Cleveland, OH Rochester, MN Lars Svensson & Murat Tuzcu Kevin Greason & Verghese Mathew OK Cardiology Research Scripps Green Hospital 19 9 Oklahoma City, OK La Jolla, CA Mark Bodenhamer & Mohammad Ghani Scot Brewster & Paul Teirstein
PARTNER II Inoperable Cohort Enrollment by Site (2 of 2) University of Miami William Beaumont Hospital 9 3 Miami, FL Royal Oak, MI Alan Heldman & Donald B. Williams George Hanzel & Francis Shannon University of Virginia Northwestern University 9 2 Charlottesville, VA Chicago, IL Irving Kron & Scott Lim Charles Davidson & Chris Malaisrie NorthShore University University of Texas, Houston 8 2 Evanston, IL Houston, TX Ted Feldman & Paul Pearson Anthony Estrera & Richard Smalling Rush University Massachusetts General Hospital 8 1 Chicago, IL Boston, MA Zyiad M. Hijazi & Robert March Igor Palacios & Gus Vlahakes Minneapolis Heart Institute 7 Minneapolis, MN Vibhu Kshettry & Wesley Pedersen St. Luke’s Hospital (MAHI) 4 Kansas City, MO Michael Borkon & Adnan Chhatriwalla University of Washington 4 Seattle, WA Mark Reisman & Edward Verrier Brigham Women’s Hospital 3 Boston, MA Ralph Bolman, III & Frederick G. Welt
PARTNER II Inoperable Cohort Enrollment Cadence 600 140 Last pt enrolled: February 10, 2012 Last pt follow-up: March 1, 2013 120 500 Cumulative Enrollment 100 Monthly Enrollment 400 80 300 120 60 200 40 74 60 58 57 55 100 42 41 20 29 23 1 0 0 Apr-11 May-11 Jun-11 Jul-11 Aug-11 Sep-11 Oct-11 Nov-11 Dec-11 Jan-12 Feb-12
Recommend
More recommend
