Clinical trial NCT03222128: PARTNER II Trial: Placement of AoRTic TraNscathetER Valves II - S3 Intermediate
Official title: Edwards SAPIEN 3 Transcatheter Heart Valve Therapy for Intermediate Risk Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Symptomatic Severe Aortic Stenosis
Keywords: SAPIEN 3
Transfemoral
Transapical
Transaortic
NovaFlex
TAVI
Aortic Stenosis
THV
Aortic Valve
Transcatheter Heart Valve
TAVR
Lead sponsor: Edwards Lifesciences
Sponsor class: INDUSTRY
First posted: 2017-07-19
Enrollment: 1074
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this trial is to determine the safety and effectiveness of the Edwards SAPIEN 3 transcatheter heart valve and delivery systems which are intended for use in patients with symptomatic, calcific, and severe aortic stenosis, and those with intermediate risk.

Detailed description: This study design consists of PIIS3i cohort.

The PIIS3i cohort is a single arm non-randomized, historical-controlled study. Patients recruited to the treatment arm will receive an Edwards SAPIEN 3 THV with either transfemoral, transapical or transaortic delivery access.

To ensure that patients are of "intermediate" risk, an STS score of 4 - 8% has been selected.

Eligibility criteria: Inclusion Criteria

1. Patient has senile degenerative aortic valve stenosis with echocardiographically derived criteria: mean gradient \>40 mmHg or jet velocity greater than 4.0 m/s and an initial aortic valve area (AVA) of \<0.8 cm2 or indexed EOA \< 0.5 cm2/m2 Qualifying echo must be within 60 days of the date of the procedure.
2. Patient is symptomatic from his/her aortic valve stenosis, as demonstrated by NYHA Functional Class II or greater.
3. The heart team agrees (and verified in the case review process) that valve implantation will likely benefit the patient.
4. The study patient or the study patient's legal representative 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.
5. The study patient agrees to comply with all required post-procedure follow-up visits including annual visits through 5 years and analysis close date visits, which will be conducted as a phone follow-up.

Exclusion Criteria:

1. Heart team assessment of inoperability (including examining cardiac surgeon).
2. Complex coronary artery disease

   1. Unprotected left main coronary artery
   2. Syntax score \> 32 (in the absence of prior revascularization)
3. Hemodynamic or respiratory instability requiring inotropic support, mechanical ventilation, or mechanical heart assistance within 30 days of screening evaluation.
4. Need for emergency surgery for any reason.

Primary outcomes:
measure: Number of Participants With Composite of All-cause Death, All Stroke and Aortic Insufficiency (AI) ≥ Moderate
timeFrame: 1 year
Secondary outcomes:
measure: Composite of All-cause Death, All Stroke, Life Threatening (Disabling)/ Major Bleeding and Major Vascular Complication at 30 Days
timeFrame: 30 Days
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Scripps Green Hospital
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Sacramento
country: United States
facility: Mercy General Hospital
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Denver
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Clearwater
country: United States
facility: Morton Plant Hospital
state: Florida
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Evanston
country: United States
facility: Northshore
state: Illinois
city: Springfield
country: United States
facility: Prairie Education and Research Cooperative
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Health-Methodist Hospital
state: Indiana
city: Indianapolis
country: United States
facility: St. Vincent Medical Group, Inc./St. Vincent Heart Center of Indiana, LLC
state: Indiana
city: Iowa City
country: United States
facility: The University of Iowa
state: Iowa
city: Louisville
country: United States
facility: The Jewish Hospital Medical Center
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland, Baltimore
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute Foundation
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic-Saint Marys Hospital
state: Minnesota
city: Kansas City
country: United States
facility: St. Luke's Hospital - Mid America Heart Institute
state: Missouri
city: Saint Louis
country: United States
facility: Washington University - Barnes Jewish Hospital
state: Missouri
city: Lincoln
country: United States
facility: Nebraska Heart Institute
state: Nebraska
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: New Hyde Park
country: United States
facility: Northshore Long Island Jewish Health System
state: New York
city: New York
country: United States
facility: Cornell University
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Greenville
country: United States
facility: East Carolina Heart Institute at East Carolina University
state: North Carolina
city: Cincinnati
country: United States
facility: The Lindner Center for Research & Education at The Christ Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Cardiovascular Research Group
state: Oklahoma
city: Portland
country: United States
facility: Providence Heart & Vascular Institute at Providence St. Vincent Medical Center
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania Hospital
state: Pennsylvania
city: York
country: United States
facility: York Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Austin
country: United States
facility: Austin Heart, PLLC
state: Texas
city: Dallas
country: United States
facility: The Heart Hospital Baylor Plano
state: Texas
city: Dallas
country: United States
facility: Medical City Dallas
state: Texas
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio (UTHSCSA)
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Norfolk
country: United States
facility: Sentara Norfolk General Hospital
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Madison
country: United States
facility: University of Wisconsin - Madison
state: Wisconsin
Study officials:
affiliation: Columbia University
name: Martin B Leon, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Columbia University
name: Craig Smith, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vincent F, Thourani VH, Ternacle J, Redfors B, Cohen DJ, Hahn RT, Li D, Crowley A, Webb JG, Mack MJ, Kapadia S, Russo M, Smith CR, Alu MC, Leon MB, Pibarot P. Time-of-Day and Clinical Outcomes After Surgical or Transcatheter Aortic Valve Replacement: Insights From the PARTNER Trials. Circ Cardiovasc Qual Outcomes. 2022 Jan;15(1):e007948. doi: 10.1161/CIRCOUTCOMES.121.007948. Epub 2022 Jan 18.
citation: Herrmann HC, Cohen DJ, Hahn RT, Babaliaros VC, Yu X, Makkar R, McCabe J, Szerlip M, Kapadia S, Russo M, Malaisrie SC, Webb JG, Szeto WY, Kodali S, Thourani VH, Mack MJ, Leon MB. Utilization, Costs, and Outcomes of Conscious Sedation Versus General Anesthesia for Transcatheter Aortic Valve Replacement. Circ Cardiovasc Interv. 2021 Jul;14(7):e010310. doi: 10.1161/CIRCINTERVENTIONS.120.010310. Epub 2021 Jun 16.
citation: Brener MI, George I, Kosmidou I, Nazif T, Zhang Z, Dizon JM, Garan H, Malaisrie SC, Makkar R, Mack M, Szeto WY, Fearon WF, Thourani VH, Leon MB, Kodali S, Biviano AB. Atrial Fibrillation Is Associated With Mortality in Intermediate Surgical Risk Patients With Severe Aortic Stenosis: Analyses From the PARTNER 2A and PARTNER S3i Trials. J Am Heart Assoc. 2021 Apr 6;10(7):e019584. doi: 10.1161/JAHA.120.019584. Epub 2021 Mar 23.
citation: Ong G, Pibarot P, Redfors B, Weissman NJ, Jaber WA, Makkar RR, Lerakis S, Gopal D, Khalique O, Kodali SK, Thourani VH, Anwaruddin S, McAndrew T, Zhang Y, Alu MC, Douglas PS, Hahn RT. Diastolic Function and Clinical Outcomes After Transcatheter Aortic Valve Replacement: PARTNER 2 SAPIEN 3 Registry. J Am Coll Cardiol. 2020 Dec 22;76(25):2940-2951. doi: 10.1016/j.jacc.2020.10.032.
citation: Pibarot P, Ternacle J, Jaber WA, Salaun E, Dahou A, Asch FM, Weissman NJ, Rodriguez L, Xu K, Annabi MS, Guzzetti E, Beaudoin J, Bernier M, Leipsic J, Blanke P, Clavel MA, Rogers E, Alu MC, Douglas PS, Makkar R, Miller DC, Kapadia SR, Mack MJ, Webb JG, Kodali SK, Smith CR, Herrmann HC, Thourani VH, Leon MB, Hahn RT; PARTNER 2 Investigators. Structural Deterioration of Transcatheter Versus Surgical Aortic Valve Bioprostheses in the PARTNER-2 Trial. J Am Coll Cardiol. 2020 Oct 20;76(16):1830-1843. doi: 10.1016/j.jacc.2020.08.049.
citation: Chen S, Redfors B, O'Neill BP, Clavel MA, Pibarot P, Elmariah S, Nazif T, Crowley A, Ben-Yehuda O, Finn MT, Alu MC, Vahl TP, Kodali S, Leon MB, Lindman BR. Low and elevated B-type natriuretic peptide levels are associated with increased mortality in patients with preserved ejection fraction undergoing transcatheter aortic valve replacement: an analysis of the PARTNER II trial and registry. Eur Heart J. 2020 Feb 21;41(8):958-969. doi: 10.1093/eurheartj/ehz892.
citation: Summers MR, Leon MB, Smith CR, Kodali SK, Thourani VH, Herrmann HC, Makkar RR, Pibarot P, Webb JG, Leipsic J, Alu MC, Crowley A, Hahn RT, Kapadia SR, Tuzcu EM, Svensson L, Cremer PC, Jaber WA. Prosthetic Valve Endocarditis After TAVR and SAVR: Insights From the PARTNER Trials. Circulation. 2019 Dec 10;140(24):1984-1994. doi: 10.1161/CIRCULATIONAHA.119.041399. Epub 2019 Nov 6.
citation: Furer A, Chen S, Redfors B, Elmariah S, Pibarot P, Herrmann HC, Hahn RT, Kodali S, Thourani VH, Douglas PS, Alu MC, Fearon WF, Passeri J, Malaisrie SC, Crowley A, McAndrew T, Genereux P, Ben-Yehuda O, Leon MB, Burkhoff D. Effect of Baseline Left Ventricular Ejection Fraction on 2-Year Outcomes After Transcatheter Aortic Valve Replacement: Analysis of the PARTNER 2 Trials. Circ Heart Fail. 2019 Aug;12(8):e005809. doi: 10.1161/CIRCHEARTFAILURE.118.005809. Epub 2019 Aug 1.
citation: Nazif TM, Chen S, George I, Dizon JM, Hahn RT, Crowley A, Alu MC, Babaliaros V, Thourani VH, Herrmann HC, Smalling RW, Brown DL, Mack MJ, Kapadia S, Makkar R, Webb JG, Leon MB, Kodali SK. New-onset left bundle branch block after transcatheter aortic valve replacement is associated with adverse long-term clinical outcomes in intermediate-risk patients: an analysis from the PARTNER II trial. Eur Heart J. 2019 Jul 14;40(27):2218-2227. doi: 10.1093/eurheartj/ehz227.