PARTNER 3 Trial: Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve in Low Risk Patients With Aortic Stenosis (P3)

• ClinicalTrials.gov Identifier: NCT02675114
• Recruitment Status: Active, not recruiting
• First Posted: February 5, 2016
• Results First Posted: December 2, 2021
• Last Update Posted: November 30, 2023
• Sponsor: Edwards Lifesciences
• Information provided by (Responsible Party): Edwards Lifesciences

Tracking Information

• First Submitted Date: January 22, 2016
• First Posted Date: February 5, 2016
• Results First Submitted Date: October 7, 2021
• Results First Posted Date: December 2, 2021
• Last Update Posted Date: November 30, 2023
• Actual Study Start Date: March 2016
• Actual Primary Completion Date: November 16, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 23, 2021)

All-cause Mortality, All Stroke, and Rehospitalization (Valve-related or Procedure-related and Including Heart Failure) [ Time Frame: 1 year ]

Number of patients that had any of these events

Original Primary Outcome Measures (submitted: February 2, 2016)

All-cause mortality, all stroke, and re-hospitalization [ Time Frame: 1 year post procedure ]

This composite endpoint will be evaluated as a non-inferiority analysis based on a relative non-inferiority margin of 35%

Current Secondary Outcome Measures (submitted: November 23, 2021)

• New Onset Atrial Fibrillation [ Time Frame: 30 days ]
  Number of patients with this event
• Length of Index Hospitalization [ Time Frame: Discharge (expected average of 7 days) ]
  Number of days from index procedure to discharge
• Death, Kansas City Cardiomyopathy Questionnaire (KCCQ) Score < 45 or KCCQ Score Decrease ≥ 10 Points [ Time Frame: 30 days ]
  Number of patients that had any of these events
• Death or Stroke [ Time Frame: 30 days ]
  Number of patients that died or had a stroke
• All Stroke [ Time Frame: 30 days ]
  Number of patients that had a stroke

Original Secondary Outcome Measures (submitted: February 2, 2016)

• New onset atrial fibrillation [ Time Frame: 30 Days ]
• Length of index hospitalization (Device and Control group) [ Time Frame: Number of days from index procedure to discharge (expected average of 7 days) ]
• Death, KCCQ < 45 or KCCQ decrease ≥ 10 points [ Time Frame: 30 days ]
  Kansas City Cardiomyopathy Questionnaire (KCCQ) is used to assess quality of life measure for heart failure.
• Death or Stroke [ Time Frame: 30 Days ]
• Stroke (disabling and non-disabling) [ Time Frame: 30 Days ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Aortic Stenosis

Intervention

• Procedure: SAVR
  SAVR with a commercially available bioprosthetic valve.
• Device: SAPIEN 3 THV
  TAVR with the Edwards SAPIEN 3 Transcatheter Heart Valve and Edwards Commander Delivery System

Study Arms

• Active Comparator: Surgical aortic valve replacement (SAVR)
  Intervention: Procedure: SAVR
• Experimental: Transcatheter aortic valve replacement (TAVR)
  Intervention: Device: SAPIEN 3 THV

Publications *

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: May 22, 2020): 1000
• Original Estimated Enrollment (submitted: February 2, 2016): 1228
• Estimated Study Completion Date: December 2029
• Actual Primary Completion Date: November 16, 2020 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, Japan, New Zealand, United States

Administrative Information

• NCT Number: NCT02675114
• Other Study ID Numbers: 2015-08
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Edwards Lifesciences
• Original Responsible Party: Same as current
• Current Study Sponsor: Edwards Lifesciences
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Martin B Leon, MD, FACC; Columbia University Medical Center/ New York Presbyterian Hospital, NY
• Principal Investigator: Michael J Mack, MD, FACC; The Heart Hospital Baylor Plano, TX

• PRS Account: Edwards Lifesciences
• Verification Date: November 2023