Clinical trial NCT02675114: PARTNER 3 Trial: Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve in Low Risk Patients With Aortic Stenosis
Official title: A Prospective, Randomized, Controlled, Multi-Center Study to Establish the Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve in Low Risk Patients Who Have Severe, Calcific, Aortic Stenosis Requiring Aortic Valve Replacement
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Aortic Stenosis
Keywords: SAPIEN 3
cardiovascular disease
heart disease
aortic stenosis
Surgical aortic valve replacement (SAVR)
Transcatheter aortic valve replacement (TAVR)
Lead sponsor: Edwards Lifesciences
Sponsor class: INDUSTRY
First posted: 2016-02-05
Enrollment: 1000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To establish the safety and effectiveness of the Edwards SAPIEN 3 Transcatheter Heart Valve (THV) in patients with severe, calcific aortic stenosis who are at low operative risk for standard aortic valve replacement.

Detailed description: Prospective, randomized, controlled, multi-center trial. Patients having an operative mortality \< 4% (low operative risk) for surgical aortic valve replacement will be randomized 1:1 to receive either transcatheter heart valve replacement (TAVR) with the Edwards SAPIEN 3 or aortic valve replacement with a commercially available surgical bioprosthetic valve. Patients will be seen for follow-up visits at discharge, 30 days, 6 months, and annually through 10 years.

A subset of PARTNER 3 randomized patients will be enrolled in the Actigraphy/Quality of Life. Additional patients will be enrolled in either the Bicuspid Registry, Underrepresented Populations Registry (UPR) or the Alternative Access Registry.

Eligibility criteria: Inclusion Criteria:

1. Severe, calcific aortic stenosis
2. New York Heart Association Functional Class ≥ 2 OR exercise tolerance test that demonstrates a limited exercise capacity, abnormal BP response, or arrhythmia OR asymptomatic with Left Ventricular Ejection Fraction (LVEF) \<50%
3. Heart team agrees the patient has a risk of operative mortality and has an Society of Thoracic Surgeons (STS) score \< 4
4. The study patient has been informed of the nature of the study, agrees to its provisions and has provided written informed consent.

Exclusion Criteria:

1. Native aortic annulus size unsuitable for sizes 20, 23, 26, or 29 mm transcatheter heart valve
2. Iliofemoral vessel characteristics that would preclude safe passage of the introducer sheath
3. Evidence of an acute myocardial infarction ≤ 30 days before randomization
4. Aortic valve is unicuspid, bicuspid, or non-calcified
5. Severe aortic regurgitation (\>3+)
6. Severe mitral regurgitation (\>3+) ≥ moderate stenosis
7. Pre-existing mechanical or bioprosthetic valve in any position
8. Complex coronary artery disease:

   1. Unprotected left main coronary artery
   2. Syntax score \> 32
   3. Heart Team assessment that optimal revascularization cannot be performed
9. Symptomatic carotid or vertebral artery disease or successful treatment of carotid stenosis within 30 days of randomization
10. Leukopenia, anemia, thrombocytopenia, history of bleeding diathesis or coagulopathy, or hypercoagulable states
11. Hemodynamic or respiratory instability requiring inotropic support, mechanical ventilation or mechanical heart assistance within 30 days of randomization
12. Hypertrophic cardiomyopathy with obstruction
13. Ventricular dysfunction with LVEF \< 30%
14. Cardiac imaging evidence of intracardiac mass, thrombus or vegetation
15. Inability to tolerate or condition precluding treatment with antithrombotic/anticoagulation therapy during or after the valve implant procedure
16. Stroke or transient ischemic attack within 90 days of randomization
17. Renal insufficiency and/or renal replacement therapy at the time of screening.
18. Active bacterial endocarditis within 180 days of randomization
19. Severe lung disease or currently on home oxygen
20. Severe pulmonary hypertension
21. History of cirrhosis or any active liver disease
22. Significant frailty as determined by the Heart Team
23. Significant abdominal or thoracic aortic disease that would preclude safe passage of the delivery system or cannulation and aortotomy for surgical aortic valve replacement
24. Hostile chest or conditions or complications from prior surgery that would preclude safe reoperation
25. Patient refuses blood products
26. Body mass index \> 50 kg/m2
27. Estimated life expectancy \< 24 months
28. Absolute contraindications or allergy to iodinated contrast that cannot be adequately treated with pre-medication
29. Immobility that would prevent completion of study procedures
30. Patient is not a candidate for both arms of the study
31. Currently participating in an investigational drug or another device study.

Primary outcomes:
measure: All-cause Mortality, All Stroke, and Rehospitalization (Valve-related or Procedure-related and Including Heart Failure)
timeFrame: 1 year
Secondary outcomes:
measure: New Onset Atrial Fibrillation
timeFrame: 30 days
measure: Length of Index Hospitalization
timeFrame: Discharge (expected average of 7 days)
measure: Death, Kansas City Cardiomyopathy Questionnaire (KCCQ) Score < 45 or KCCQ Score Decrease ≥ 10 Points
timeFrame: 30 days
measure: Death or Stroke
timeFrame: 30 days
measure: All Stroke
timeFrame: 30 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Phoenix
country: United States
facility: Banner University Medical Center
state: Arizona
city: Burlingame
country: United States
facility: Mills/Peninsula Health Services
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles/Ronald Reagan Medical Center
state: California
city: Newport Beach
country: United States
facility: Hoag Hospital
state: California
city: Palo Alto
country: United States
facility: Stanford Hospital and Clinics
state: California
city: Sacramento
country: United States
facility: Sutter Health Sacramento
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente San Francisco
state: California
city: Loveland
country: United States
facility: UC Health Northern Colorado/Medical Center of the Rockies
state: Colorado
city: Hartford
country: United States
facility: Hartford
state: Connecticut
city: Atlantis
country: United States
facility: JFK Medical Center / Atlantic Clinical Research Collaborative
state: Florida
city: Gainesville
country: United States
facility: University of Florida, Gainesville
state: Florida
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center
state: Florida
city: Orlando
country: United States
facility: Florida Hospital
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Honolulu
country: United States
facility: The Queen's Medical Center
state: Hawaii
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 University HealthSystem Research Institute
state: Illinois
city: Springfield
country: United States
facility: Prairie Education and Research Cooperative
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Wichita
country: United States
facility: Cardiovascular Research Institute of Kansas
state: Kansas
city: New Orleans
country: United States
facility: UPR - Louisiana State University Health Science Center
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Auburn
country: United States
facility: Central Maine Medical Center
state: Maine
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: University of Minnesota Medical Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City Mid America
state: Missouri
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital / Washington University
state: Missouri
city: Lincoln
country: United States
facility: Nebraska Heart Institute
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Morristown
country: United States
facility: Morristown Medical Center / Atlantic Health System Hospital
state: New Jersey
city: Newark
country: United States
facility: Newark Beth Israel
state: New Jersey
city: Albany
country: United States
facility: Albany
state: New York
city: Buffalo
country: United States
facility: University of Buffalo
state: New York
city: Mineola
country: United States
facility: Winthrop-University Hospital
state: New York
city: New York
country: United States
facility: NYU Medical Center
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/ New York Presbyterian Hospital
state: New York
city: Charlotte
country: United States
facility: Carolina's Health System
state: North Carolina
city: Charlotte
country: United States
facility: UPR - Novant Health Heart and Vascular Institution
state: North Carolina
city: Raleigh
country: United States
facility: Rex Hospital / NC Heart and Vascular Research
state: North Carolina
city: Cincinnati
country: United States
facility: The Christ Hospital, Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Mount Carmel Health System
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Cardiovascular Research Group
state: Oklahoma
city: Tulsa
country: United States
facility: UPR-Oklahoma Heart Institute
state: Oklahoma
city: Portland
country: United States
facility: Providence Heart & Vascular Institute
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Medical Center
state: Pennsylvania
city: York
country: United States
facility: York Hospital
state: Pennsylvania
city: Memphis
country: United States
facility: Baptist Memorial Hospital
state: Tennessee
city: Nashville
country: United States
facility: Saint Thomas Health Services
state: Tennessee
city: Austin
country: United States
facility: Austin Heart
state: Texas
city: Dallas
country: United States
facility: Medical City Dallas Hospital
state: Texas
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
city: Plano
country: United States
facility: The Heart Hosptial Baylor Plano
state: Texas
city: Salt Lake City
country: United States
facility: Intermountain Medical Center
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Falls Church
country: United States
facility: Fairfax INOVA
state: Virginia
city: Norfolk
country: United States
facility: Sentara Cardiovascular Research Institute
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Vancouver
country: Canada
facility: Saint Paul's Hospital
city: Kitakyushu
country: Japan
facility: Kokura Memorial Hospital
state: Fukuoka
city: Sendai
country: Japan
facility: Sendai Kousei Hospital
state: Miyagi
city: Suita
country: Japan
facility: Osaka University
state: Osaka
city: Itabashi
country: Japan
facility: Teikyo University
state: Tokyo
city: Shinjuku
country: Japan
facility: Keio University
state: Tokyo
city: Grafton
country: New Zealand
facility: Auckland City Hospital
state: Auckland
Study officials:
affiliation: Columbia University Medical Center/ New York Presbyterian Hospital, NY
name: Martin B Leon, MD, FACC
role: PRINCIPAL_INVESTIGATOR
affiliation: The Heart Hospital Baylor Plano, TX
name: Michael J Mack, MD, FACC
role: PRINCIPAL_INVESTIGATOR
References:
citation: Genereux P, Pibarot P, Redfors B, Bax JJ, Zhao Y, Makkar RR, Kapadia S, Thourani VH, Mack MJ, Nazif TM, Lindman BR, Babaliaros V, Vincent F, Russo M, McCabe JM, Gillam LD, Alu MC, Hahn RT, Webb JG, Leon MB, Cohen DJ. Evolution and Prognostic Impact of Cardiac Damage After Aortic Valve Replacement. J Am Coll Cardiol. 2022 Aug 23;80(8):783-800. doi: 10.1016/j.jacc.2022.05.006. Epub 2022 May 17.
citation: Ternacle J, Al-Azizi K, Szerlip M, Potluri S, Hamandi M, Blanke P, Leipsic J, Dahou A, Salaun E, Vincent F, Rogers E, Alu MC, Lu M, Yu X, Thourani VH, Hahn RT, Leon MB, Pibarot P, Mack MJ. Impact of Predilation During Transcatheter Aortic Valve Replacement: Insights From the PARTNER 3 Trial. Circ Cardiovasc Interv. 2021 Jul;14(7):e010336. doi: 10.1161/CIRCINTERVENTIONS.120.010336. Epub 2021 Jun 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: Leon MB, Mack MJ, Hahn RT, Thourani VH, Makkar R, Kodali SK, Alu MC, Madhavan MV, Chau KH, Russo M, Kapadia SR, Malaisrie SC, Cohen DJ, Blanke P, Leipsic JA, Williams MR, McCabe JM, Brown DL, Babaliaros V, Goldman S, Herrmann HC, Szeto WY, Genereux P, Pershad A, Lu M, Webb JG, Smith CR, Pibarot P; PARTNER 3 Investigators. Outcomes 2 Years After Transcatheter Aortic Valve Replacement in Patients at Low Surgical Risk. J Am Coll Cardiol. 2021 Mar 9;77(9):1149-1161. doi: 10.1016/j.jacc.2020.12.052.
citation: Pibarot P, Salaun E, Dahou A, Avenatti E, Guzzetti E, Annabi MS, Toubal O, Bernier M, Beaudoin J, Ong G, Ternacle J, Krapf L, Thourani VH, Makkar R, Kodali SK, Russo M, Kapadia SR, Malaisrie SC, Cohen DJ, Leipsic J, Blanke P, Williams MR, McCabe JM, Brown DL, Babaliaros V, Goldman S, Szeto WY, Genereux P, Pershad A, Alu MC, Xu K, Rogers E, Webb JG, Smith CR, Mack MJ, Leon MB, Hahn RT; PARTNER 3 Investigators. Echocardiographic Results of Transcatheter Versus Surgical Aortic Valve Replacement in Low-Risk Patients: The PARTNER 3 Trial. Circulation. 2020 May 12;141(19):1527-1537. doi: 10.1161/CIRCULATIONAHA.119.044574. Epub 2020 Apr 10.
citation: Mack MJ, Leon MB, Thourani VH, Makkar R, Kodali SK, Russo M, Kapadia SR, Malaisrie SC, Cohen DJ, Pibarot P, Leipsic J, Hahn RT, Blanke P, Williams MR, McCabe JM, Brown DL, Babaliaros V, Goldman S, Szeto WY, Genereux P, Pershad A, Pocock SJ, Alu MC, Webb JG, Smith CR; PARTNER 3 Investigators. Transcatheter Aortic-Valve Replacement with a Balloon-Expandable Valve in Low-Risk Patients. N Engl J Med. 2019 May 2;380(18):1695-1705. doi: 10.1056/NEJMoa1814052. Epub 2019 Mar 16.
citation: Leipsic J, Bax JJ, Webb JG, Martin R, Blanke P. Trials Testing the Value of Imaging Use in Valve Disease and in Transcatheter Valvular Interventions. JACC Cardiovasc Imaging. 2017 Mar;10(3):286-295. doi: 10.1016/j.jcmg.2016.09.031.