A Clinical Trial Assessing the Safety and Effectiveness of the DurAVR® THV System (PARADIGM)

A Prospective Randomized Trial Assessing the Safety and Effectiveness of the DurAVR® Biomimetic Valve Designed for Physiologic Flow Compared to Commercial TAVR Devices

Prospective, randomized, controlled, multicenter, international study.

Up to 1054 subjects with a severe native calcific aortic stenosis who are determined by the local Heart Team to have an indication for Transcatheter Aortic Valve Replacement (TAVR), will be enrolled in the 'All Comers Randomized Cohort'. Subjects will be randomized 1:1 to receive either the DurAVR® THV System or any commercially available and approved Transcatheter Heart Valve (THV) from the SAPIEN series or the Evolut series and followed for 10 years.

After completion of the All Comers Randomized Cohort, up to 446 additional low-risk subjects will be randomized 1:1 in the 'Low Risk Randomized Continued Access Cohort'.

Up to 150 subjects with a failed surgical bioprosthesis who are deemed high surgical risk and who need valve-in-valve (ViV) TAVR will be enrolled in a separate nested registry (ViV Registry Cohort) and followed for 5 years. Subjects in the ViV Registry Cohort will only receive the DurAVR® THV.

Study Overview

• Status: Recruiting
• Conditions: Severe Aortic Stenosis; Valve-in-valve Procedures
• Intervention / Treatment: Device: TAVR with SAPIEN THV series or the Evolut THV series; Device: TAVR with DurAVR® THV

• Study Type: Interventional
• Enrollment (Estimated): 1650
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jennifer Englund; Phone Number: 612 895 5257; Email: JEnglund@anteristech.com

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Recruiting
    • Aarhus University Hospital
    • Contact: Christian J Terkelsen, Prof, MD, DmSc, PhD; Phone Number: 24288571; Email: christian.terkelsen@skejby.rm.dk
  • Capital Region of Denmark
    • Copenhagen, Capital Region of Denmark, Denmark, 2100
      • Recruiting
      • Rigshospitalet
      • Contact: Ole De Backer, MD, PhD, MBA; Phone Number: +45 3545 7086; Email: ole.debacker@gmail.com
• United States
  • California
    • San Francisco, California, United States, 94118
      • Recruiting
      • Kaiser Permanente San Francisco
      • Contact: Jacob Mishell, MD; Phone Number: 415-202-3800; Email: Jacob.Mishell@kp.org
  • New York
    • The Bronx, New York, United States, 10467
      • Recruiting
      • Montefiore Medical Center
      • Contact: Andrea Scotti, MD; Phone Number: 718-904-3442; Email: ascotti@montefiore.org
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Recruiting
      • The Stern Cardiovascular Foundation
      • Contact: Basil Paulus, MD; Phone Number: 901-271-1000; Email: basil.paulus@sterncardio.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Native Aortic Stenosis Cohorts:

1. The subject is a candidate for TAVR using the DurAVR® THV System, and a SAPIEN series THV system or an Evolut series THV System.
2. The local Heart Team agrees that the subject has an appropriate indication for, and will benefit from, TAVR due to native calcific valve severe aortic stenosis.
3. Subject understands the study requirements and the treatment procedure and provides written informed consent.

ViV Registry Cohort:

1. Severe degeneration of a surgically implanted aortic bioprosthetic valve.
2. Subject requires aortic valve replacement and is high surgical risk and is indicated for TAVR Valve-in-Valve procedure as determined by the Heart Team.
3. Subject understands the study requirements and the treatment procedure and provides written informed consent.

Exclusion Criteria:

Native Aortic Stenosis Cohorts:

1. Native aortic annulus size unsuitable for study THVs (investigational or control) based on CT imaging analysis.
2. Access vessel characteristics that would preclude safe placement of the introducer sheath (investigational or control).
3. Evidence of an acute myocardial infarction 30 days before randomization.
4. AV is unicuspid, Type 0 bicuspid, or is non-calcified.
5. Severe total aortic regurgitation
6. Severe mitral or tricuspid regurgitation or ≥ moderate mitral stenosis.
7. Pre-existing mechanical or bioprosthetic valve in any position.
8. Untreated clinically significant coronary artery disease (CAD) requiring revascularization.
9. Cardiac imaging evidence of intracardiac mass, thrombus, or vegetation.
10. Active bacterial endocarditis in the last 3 months.
11. Estimated life expectancy (after TAVR) <12 months.
12. Subject is not a candidate for both arms (investigational and control) of the study.
13. Subject belongs to a vulnerable population

ViV Registry Cohort:

1. Anatomy precluding safe placement of DurAVR THV.
2. Pre-existing prosthetic heart valve in the mitral, tricuspid or pulmonary position.
3. Severe mitral or tricuspid regurgitation or ≥ moderate mitral stenosis
4. Cardiac imaging evidence of intracardiac mass, thrombus or vegetation.
5. Failing surgical aortic bioprosthesis is unstable, rocking, or not structurally intact.
6. Evidence of an acute myocardial infarction ≤ 30 days before the intended treatment.
7. Untreated clinically significant coronary artery disease (CAD) requiring revascularization.
8. Need for emergency surgery for any reason
9. GI bleeding within the past 3 months.
10. Active bacterial endocarditis in the last 3 months.
11. Estimated life expectancy (after TAVR) <12 months.
12. Subject belongs to a vulnerable population.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DurAVR THV; DurAVR® THV implantation	Device: TAVR with DurAVR® THV; Transcatheter aortic valve replacement (TAVR)
Active Comparator: Control; SAPIEN THV series or the Evolut THV series implantation	Device: TAVR with SAPIEN THV series or the Evolut THV series; Transcatheter aortic valve replacement (TAVR)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite of all-cause mortality, all stroke and cardiovascular hospitalization	Composite of all-cause mortality, all stroke and cardiovascular hospitalization	1 Year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality	Mortality from any cause will by collected by tracking patient's living status via medical record	30 Days
Disabling stroke according to VARC-3 Guidelines	The precise categorization is outlined in the Valve Academic Research Consortium-3 (VARC-3) criteria.	30 Days
Life-threatening bleeding according to VARC-3 Guidelines	The precise categorization is outlined in the Valve Academic Research Consortium-3 (VARC-3) criteria.	30 Days
Major vascular complication according to VARC-3 Guidelines	The precise categorization is outlined in the Valve Academic Research Consortium-3 (VARC-3) criteria.	30 Days
Acute Kidney Injury (Stage III or IV) according to VARC-3 Guidelines	The precise categorization is outlined in the Valve Academic Research Consortium-3 (VARC-3) criteria.	30 Days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
New Permanent Pacemaker Implantation (PPI)	New pacemaker implantation in subjects experiencing conduction abnormalities	30 Days and 1 Year
Valve-related dysfunction requiring a repeat procedure	New intervention due to the valve not properly functioning	30 Days and 1 Year
Non-Structural Valve Dysfunction	Any abnormality, not intrinsic to the prosthetic valve, resulting in the valve not properly functioning	30 Days and 1 Year
Prosthesis-Patient Mismatch	Calculated in percentage	30 Days and 1 Year
Aortic Regurgitation (AR)	AR grading: None/Trace, Mild, Moderate, Severe	30 Days and 1 Year
Mean Aortic Valve (AV) Gradient	Mean Aortic Valve pressure gradient in mm Hg	30 Days and 1 Year
Doppler Velocity Index (DVI)	Doppler Velocity Index	30 Days and 1 Year
New York Heart Association (NYHA) Class	NYHA Class graded as I, II, III or IV	30 Days and 1 Year

Collaborators and Investigators

• Sponsor: Anteris Technologies Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): March 1, 2038

Study Registration Dates

• First Submitted: September 5, 2025
• First Submitted That Met QC Criteria: September 18, 2025
• First Posted (Actual): September 26, 2025

Study Record Updates

• Last Update Posted (Actual): June 10, 2026
• Last Update Submitted That Met QC Criteria: June 9, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: tavr; severe calcific aortic stenosis; failed surgical bioprosthesis
• Additional Relevant MeSH Terms: Aortic Valve Disease; Cardiovascular Diseases; Heart Diseases; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Aortic Valve, Calcification of
• Other Study ID Numbers: SP0083

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes