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

Conditions

Aortic Stenosis

Keywords

SAPIEN 3, cardiovascular disease, heart disease, aortic stenosis, Surgical aortic valve replacement (SAVR), Transcatheter aortic valve replacement (TAVR)

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.

Leon MB, Mack MJ, Pibarot P, Hahn RT, Thourani VH, Kodali SH, Généreux P, Kapadia SR, Cohen DJ, Pocock SJ, Zhang Y, Szerlip M, Ternacle J, Malaisrie SC, Herrmann HC, Szeto WY, Russo MJ, Babaliaros V, Nazif T, Webb JG, Makkar RR, PARTNER 3 Investigators.

2025-10-27

10.1056/nejmoa2509766

5-Year Echocardiographic Results of Transcatheter Versus Surgical Aortic Valve Replacement in Low-Risk Patients.

Hahn RT, Ternacle J, Silva I, Giuliani C, Zanuttini A, Théron A, Cristell N, Bernier M, Skaf S, Beaudoin J, Kodali SK, Russo M, Kapadia SR, Malaisrie CS, Cohen DJ, Leipsic J, Blanke P, Williams MR, McCabe JM, Brown DL, Babaliaros V, Goldman S, Szeto WY, Généreux P, Pershad A, Park B, Gunnarsson M, Webb JG, Smith CR, Makkar R, Thourani VH, Mack MJ, Leon MB, Pibarot P, PARTNER 3 Investigators.

2025-04-162 citations

10.1016/j.jcmg.2025.01.015

Transcatheter aortic valve implantation versus surgical aortic valve replacement in severe aortic stenosis patients at low surgical mortality risk: a cost-effectiveness analysis in Belgium.

Dubois C, Adriaenssens T, Annemans L, Bosmans J, Callebaut B, Candolfi P, Cornelis K, Delbaere A, Green M, Kefer J, Lancellotti P, Rosseel M, Shore J, Van Der Heyden J, Vermeersch S, Wyffels E.

2023-11-2118 citations

10.1080/00015385.2023.2282283

Transcatheter Aortic-Valve Replacement in Low-Risk Patients at Five Years

Michael J. Mack, Martin B. Leon, Vinod H. Thourani, Philippe Pîbarot, Rebecca T. Hahn et al. (23 authors)

New England Journal of Medicine2023-10-24491 citations

10.1056/nejmoa2307447

Cardiac Damage and Quality of Life After Aortic Valve Replacement in the PARTNER Trials.

Généreux P, Cohen DJ, Pibarot P, Redfors B, Bax JJ, Zhao Y, Prince H, Makkar RR, Kapadia S, Thourani VH, Mack MJ, Nazif TM, Lindman BR, Babaliaros V, Russo M, McCabe JM, Gillam LD, Alu MC, Hahn RT, Webb JG, Leon MB, Arnold SV.

2023-02-0140 citations

10.1016/j.jacc.2022.11.059

Cost-Effectiveness of SAPIEN 3 Transcatheter Aortic Valve Implantation Versus Surgical Aortic Valve Replacement in German Severe Aortic Stenosis Patients at Low Surgical Mortality Risk.

Kuck KH, Leidl R, Frankenstein L, Wahlers T, Sarmah A, Candolfi P, Shore J, Green M.

2023-01-0913 citations

10.1007/s12325-022-02392-y

Evolution and Prognostic Impact of Cardiac Damage After Aortic Valve Replacement.

Généreux 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.

2022-05-17113 citations

10.1016/j.jacc.2022.05.006

Impact of Predilation During Transcatheter Aortic Valve Replacement: Insights From the PARTNER 3 Trial

Julien Ternacle, Karim Al‐Azizi, Molly Szerlip, Srinivasa Potluri, Mohanad Hamandi et al. (19 authors)

Circulation Cardiovascular Interventions2021-06-1812 citations

10.1161/circinterventions.120.010336

Utilization, Costs, and Outcomes of Conscious Sedation Versus General Anesthesia for Transcatheter Aortic Valve Replacement

Howard C. Herrmann, David J. Cohen, Rebecca T. Hahn, Vasilis Babaliaros, Yu Xiao et al. (17 authors)

Circulation Cardiovascular Interventions2021-06-1622 citations

10.1161/circinterventions.120.010310

Outcomes 2 Years After Transcatheter Aortic Valve Replacement in Patients at Low Surgical Risk.

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.

2021-03-01218 citations

10.1016/j.jacc.2020.12.052

Echocardiographic Results of Transcatheter Versus Surgical Aortic Valve Replacement in Low-Risk Patients

Philippe Pîbarot, Erwan Salaün, Abdellaziz Dahou, Eleonora Avenatti, Ezéquiel Guzzetti et al. (38 authors)

Circulation2020-04-10132 citations

10.1161/circulationaha.119.044574

Transcatheter Aortic-Valve Replacement with a Balloon-Expandable Valve in Low-Risk Patients

Michael J. Mack, Martin B. Leon, Vinod H. Thourani, Raj Makkar, Susheel Kodali et al. (25 authors)

New England Journal of Medicine2019-03-164,593 citations

10.1056/nejmoa1814052

Trials Testing the Value of Imaging Use in Valve Disease and in Transcatheter Valvular Interventions.

Leipsic J, Bax JJ, Webb JG, Martin R, Blanke P.

2017-03-014 citations

10.1016/j.jcmg.2016.09.031

Interventions

PROCEDURESAVR

SAVR with a commercially available bioprosthetic valve.

DEVICESAPIEN 3 THV

TAVR with the Edwards SAPIEN 3 Transcatheter Heart Valve and Edwards Commander Delivery System

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Healthy volunteers

No

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.

Design outcomes

Primary

Measure	Time frame	Description
All-cause Mortality, All Stroke, and Rehospitalization (Valve-related or Procedure-related and Including Heart Failure)	1 year	Number of patients that had any of these events

Secondary

Measure	Time frame	Description
New Onset Atrial Fibrillation	30 days	Number of patients with this event
Length of Index Hospitalization	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	30 days	Number of patients that had any of these events
Death or Stroke	30 days	Number of patients that died or had a stroke
All Stroke	30 days	Number of patients that had a stroke

Countries

Australia, Canada, Japan, New Zealand, United States

Participant flow

Participants by arm

Arm	Count
Surgical Aortic Valve Replacement (SAVR) SAVR with a commercially available bioprosthetic valve.	454
Transcatheter Aortic Valve Replacement (TAVR) TAVR with the Edwards SAPIEN 3 Transcatheter Heart Valve and Edwards Commander Delivery System	496
Total	950

Baseline characteristics

Characteristic	Surgical Aortic Valve Replacement (SAVR)	Transcatheter Aortic Valve Replacement (TAVR)	Total
Age, Continuous	73.6 years STANDARD_DEVIATION 6.08	73.3 years STANDARD_DEVIATION 5.83	73.4 years STANDARD_DEVIATION 5.95
Race/Ethnicity, Customized Asian	9 Participants	8 Participants	17 Participants
Race/Ethnicity, Customized Black or African American	12 Participants	15 Participants	27 Participants
Race/Ethnicity, Customized Hispanic or Latino	9 Participants	7 Participants	16 Participants
Race/Ethnicity, Customized Multiple	6 Participants	3 Participants	9 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	4 Participants	5 Participants	9 Participants
Race/Ethnicity, Customized Other	4 Participants	0 Participants	4 Participants
Race/Ethnicity, Customized Unknown	1 Participants	0 Participants	1 Participants
Race/Ethnicity, Customized White	409 Participants	458 Participants	867 Participants
Sex: Female, Male Female	131 Participants	161 Participants	292 Participants
Sex: Female, Male Male	323 Participants	335 Participants	658 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	11 / 454	5 / 496
other Total, other adverse events	305 / 454	133 / 496
serious Total, serious adverse events	221 / 454	153 / 496

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Surgical Aortic Valve Replacement (SAVR)	New Onset Atrial Fibrillation	145 Participants
Transcatheter Aortic Valve Replacement (TAVR)	New Onset Atrial Fibrillation	21 Participants

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

Conditions

Keywords

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Participants by arm

Baseline characteristics

Adverse events

Outcome results

All-cause Mortality, All Stroke, and Rehospitalization (Valve-related or Procedure-related and Including Heart Failure)

All Stroke

Death, Kansas City Cardiomyopathy Questionnaire (KCCQ) Score < 45 or KCCQ Score Decrease ≥ 10 Points

Death or Stroke

Length of Index Hospitalization

New Onset Atrial Fibrillation