Comparison of Evolut FX Versus Sapien 3 Ultra Resilia. (COMPARE-TAVI)

Randomized Comparison of Evolut FX Versus Sapien 3 Ultra Resilia. The Compare-TAVI 2 Trial

To compare outcome in patients randomized to treatment with Evolut FX versus Sapien 3 Ultra Resilia.

Study Overview

• Status: Recruiting
• Conditions: Aortic Stenosis
• Intervention / Treatment: Device: Medtronic Evolut FX; Device: Edwards Sapien 3 Ultra Resilia

Detailed Description

The purpose of the "Compare-TAVI" organization is to ensure a continuous comparison of the TAVI-valves implanted, and to monitor long-term valve performances.

Purpose of present study:

To compare outcome in patients randomized to treatment with Evolut FX versus Sapien 3 Ultra Resilia.

Hypotheses:

1. Evolut FX is non-inferior to Edwards Sapien 3 Resilia with regard to the combined endpoint (death, stroke, moderate/severe aortic regurgitation, moderate/severe valve deterioration) between the two valves being compared.
2. There is no difference between valves in secondary safety and efficacy endpoints (see below)
3. There is no difference in Aortic Regurgitation fraction (ARF) and Effective Orifice Area (EOA) measured by CMR (CMR-substudy, N=166)
4. There is no difference in EOA measured invasively during dobutamine stress (hemodynamic substudy, N=440).
5. There is no difference in occurrence of Hypoathenuated Leaflet Thickening (HALT) measured by CT (CT-substudy, N=778).

• Study Type: Interventional
• Enrollment (Estimated): 1346
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christian J Terkelsen, Professor; Phone Number: +4540135388; Email: CHRITERK@RM.DK
• Study Contact Backup: Name: Helle Bargsteen; Phone Number: +4578452112; Email: hellbarg@rm.dk

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Recruiting
    • Department of Cardiology, Aarhus University Hospital
    • Contact: Christian J Terkelsen, Prof; Phone Number: 004540135388

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Patient more than 18 years of age.
2. Patient eligible for both Evolut FX and Edwards Sapien 3 Ultra Resilia according to a TAVI heart team conference.
3. The center experience for each of the valves considered should be more than 15 cases a year, and the treating physician should have implanted at least 15 of each valve used in the trial.
4. The center volume should be more than 75 cases a year.
5. The patient has given signed informed consent.
6. TAVI performed via the femoral artery.

Exclusion Criteria:

None

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Medtronic Evolut FX; TAVI procedure performed with Medtronic Evolut FX	Device: Medtronic Evolut FX; TAVI performed with Medtronic Evolut FX
Active Comparator: Edwards Sapien Ultra 3 Resilia; TAVI procedure performed with Edwards Sapien Ultra 3 Resilia	Device: Edwards Sapien 3 Ultra Resilia; TAVI performed with Edwards Sapien 3 Ultra Resilia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality, stroke, moderate/major aortic regurgitation, moderate/severe THV deterioration	The primary composite endpoint is at one-year, and a non-inferiority test is performed. See separate statistical analysis plan. Separate analyses of each component of the primary outcome will be presented, in accordance with the FDA guidelines and EMA guidelines, i.e. mortality, stroke, moderate/severe aortic regurgitation and moderate/severe THV deterioration to better understand their contribution to the primary endpoint. If non-inferiority is proven for the primary composite endpoint, a split alfa is used to test for superiority if possible (alfa=0.025) and to test secondary safety and efficacy endpoints (Total alfa=0.025 for these). The composite endpoint will be re-analyzed after 3-, 5- and 10-year as superiority analyses.	1-year, 3-year, 5-year, 10-year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TAVI-related complications	conversion to open surgery during implantation, unplanned use of cardiopulmonary support (CPS), coronary artery obstruction, ventricular septal perforation, mitral valve apparatus damage or dysfunction, cardiac tamponade / pericardial effusion resulting in pericardiocentesis, valve embolization, valve migration, need for TAVI-in-TAVI deployment, using VARC-3 criteria 10, or annulus rupture, aortic rupture/perforation, aortic dissection, or other shunts than VSD.	7-days
Proportion with successful implantation of the chosen valve.	This means no need for more than 1 TAVI valve, no change to another valve than planned during the procedure because it was impossible to implant the valve planned, and no conversion to surgery or procedure-related death.	7-days
SMART criteria for bioprosthetic valve dysfunction through 12 months	composed of the following components: (1) hemodynamic structural valve dysfunction, defined as aortic valve mean gradient ≥ 20 mmHg at any time up to the 12-month visit echo; (2) nonstructural valve dysfunction, defined as severe prosthesis-patient mismatch or ≥ moderate total aortic regurgitation at any time up to the 12-month visit echo; (3) clinical valve thrombosis; (4) endocarditis; or (5) aortic valve reintervention.	1-year
Pacemaker-implantation	New pace-maker implantation in pacemaker-naive patients.	1-year
Vascular and access-related complications (exploratory only)	Major vascular access site and access-related complications resulting in endovascular or open surgery using VARC-3 criteria	30-days
Bleeding and transfusion (exploratory only)	Major bleeding resulting in drop in hgb-level ≥1.86 mmol/l and/or erythrocyte transfusion ≥ 2 units, modified from BARC type 3-5 criteria	30-days
Endocarditis (exploratory only)	According to VARC-3 criteria.	30-day, 1-year, 3-year, 5-year, 10-year
Reoperation (exploratory only)	Transcatheter Aortic Valve Intervention, Surgical Aortic Valve Intervention or Balloon Angioplasty	30-day, 1-year, 3-year, 5-year, 10-year
Mean gradient (exploratory only)	Aortic mean gradient, mmHg, as evaluated by Echocardiograpy Core-laboratory.	30-day, 1-year, 3-year, 5-year, 10-year
Pacemaker-implantation (exploratory only)	New pacemaker in pacemaker naive-patients.	30-day prior to TAVI, 30-day, 1-year, 3-year, 5-year, 10-year
Readmission for congestive heart failure (exploratory only)	Adjudicated. Only monitored until first confirmed case.	30-day, 1-year, 3-year, 5-year, 10-year.
AMI (exploratory only)	Acute Myocardial Infarction. Adjudicated. Only monitored until first confirmed case.	30-day, 1-year, 3-year, 5-year, 10-year.
Revascularization (exploratory only)	PCI (Percutaneous coronary intervention) CABG (Coronary Artery Bypass Grafting), not scheduled before TAVI	30-day, 1-year, 3-year, 5-year, 10-year.
Atrial fibrillation (exploratory only)	Newly diagnosed atrial fibrillation/flutter	30-day, 1-year, 3-year, 5-year, 10-year.
Kidney injury (exploratory only)	Increase in renal creatinine level more than to ≥200% (AKIN stage 2-3, VARC-3 criteria) or resulting in dialysis (AKIN stage 4) according to VARC-3 criteria.	30-day
Moderate/severe prosthesis-patient mismatch (exploratory only)	Effective Orifice Area (EOA)/body surface area ≤0.85 cm2/m2 if BMI<30 kg/cm2 or <=0.70 cm2/m2 if BMI>=30 kg/cm2., according to VARC-3 criteria.	30-day

Collaborators and Investigators

• Sponsor: Christian Juhl Terkelsen
• Collaborators: Department of Clinical Epidemiology, Aarhus University, DK-8200 Aarhus N, Denmark
• Investigators: Principal Investigator: christian J Terkelsen, Professor, Department of cardiology, Aarhus University Hospital, DK-8200 Aarhus N, Denmark

Publications and helpful links

General Publications

• Thim T, Nissen H, Niemela M, Eftekhari A, Jalanko M, Savontaus M, Jaaskelainen P, Hensey M, Jensen RV, Norgaard BL, Frederiksen CA, Vase HO, Pedersen L, Sorensen HT, Christiansen EH, Terkelsen CJ. Design and rationale of the COMPARE-TAVI 2 trial: An all-comers head-to-head comparison of Evolut FX+ and Sapien 3 Ultra Resilia transcatheter heart valves. Am Heart J. 2026 Feb 23;297:107387. doi: 10.1016/j.ahj.2026.107387. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): December 1, 2036

Study Registration Dates

• First Submitted: June 13, 2024
• First Submitted That Met QC Criteria: June 20, 2024
• First Posted (Actual): June 24, 2024

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Aortic Valve Disease; Cardiovascular Diseases; Heart Diseases; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis
• Other Study ID Numbers: COMPARE-TAVI-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We are willing to collaborate in meta-analyses based on individual data where department of epidemiology, Aarhus University Hospital will be responsible for data-analyses.
• IPD Sharing Time Frame: Available now. Analytic will be made available when final statistical analyses performed.
• IPD Sharing Access Criteria: Contact primary investigator
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes