Optimized Expansion of the Implanted Transcatheter Aortic Valve (OptEx-TAVI)

Optimized Expansion of the Implanted Transcatheter Aortic Valve to Reduce Hypoattenuating Leaflet Thickening in Non-atrial Fibrillation Patients Undergoing Transcatheter Aortic Valve Implantation: an International, Multicentre, Randomized Controlled Trial

Optimized Expansion of the implanted transcatheter aortic valve to reduce hypoattenuating leaflet thickening in non-atrial fibrillation patients undergoing transcatheter aortic valve implantation (TAVI): an international, multicentre, randomized controlled trial.

The objective is to evaluate whether TAVI with systematic optimized pre- and post-dilatation (optimized expansion (OptEx) TAVI strategy), compared to a standard of care (SoC) TAVI strategy, is superior in reducing hypoattenuating leaflet thickening as evaluated by cardiac computed tomography (CT) imaging at three months after TAVI.

The primary outcome is at least one thickened TAV leaflet involving ≥ 25% of the leaflet curvilinear dimension as assessed at cardiac CT at three months after TAVI.

Study Overview

• Status: Recruiting
• Conditions: Valvular Heart Disease; Aortic Stenosis Disease
• Intervention / Treatment: Procedure: SoC-TAVI; Procedure: OptEx-TAVI

Detailed Description

A total of 620 patients will be included in the OptEx-TAVI trial and randomised 1:1 to either :

• SoC-TAVI (N = 310) or
• OptEx-TAVI (N = 310)

All patients with indication for TAVI and eligible in relation to the study in- and exclusion criteria will be offered participation in the OptEx-TAVI trial.

Inclusion criteria:

• Severe symptomatic aortic stenosis patients with an indication for TAVI
• Ability to understand and to comply with the study protocol

Exclusion criteria:

• Existing indication for oral anticoagulation (e.g., atrial fibrillation, venous thromboembolism, antiphospholipid syndrome, mechanical mitral valve)
• Creatinine clearance <15 mL/min (CKD-EPI formula) or on renal replacement therapy
• Iodine contrast allergy or other condition that prohibits cardiac CT imaging

Baseline characteristics, medical history, procedural details, electrocardiogram, echocardiography and cardiac CT-scan parameters will be recorded by assessing medical charts and patient interview.

During the TAVI-procedure, patients will be treated according to randomisation to either SoC or OptEx

Planned post-procedural visits at:

• Discharge: on-site - including transthoracic echocardiography (TTE)
• 3 months visit (± 2 months): on-site - including TTE and cardiac CT scan
• 1 year (± 3 months): on-site - including TTE and cardiac CT scan
• 5 years (± 6 months): on-site - including TTE and cardiac positron emission tomography (PET)-CT scan

• Study Type: Interventional
• Enrollment (Estimated): 620
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ole De Backer, MD, PhD, FESC; Phone Number: +4535457086; Email: ole.de.backer@regionh.dk
• Study Contact Backup: Name: Troels H Jørgensen, MD, PhD; Phone Number: +4535450892; Email: troels.hoejsgaard.joergensen.01@regionh.dk

Study Locations

• Belgium
  • Charleroi, Belgium, 6000
    • Not yet recruiting
    • CHU Charleroi
    • Contact: Adel Aminian; Email: adel.aminian@chu-charleroi.be
  • Leuven, Belgium, 3000
    • Not yet recruiting
    • UZ Leuven
    • Contact: Christophe Dubois, MD, PhD; Email: christophe.dubois@uzleuven.be
• Denmark
  • Aa, Denmark, 8200
    • Not yet recruiting
    • Skejby Hospital
    • Contact: Christian J Terkelsen; Email: christian.juhl.terkelsen@clin.au.dk
  • Aalborg, Denmark, 9000
    • Not yet recruiting
    • Aalborg University Hospital
    • Contact: Ashkan Eftekhari; Email: asef@rn.dk
  • Copenhagen, Denmark
    • Recruiting
    • Rigshospitalet
    • Contact: Ole De Backer, MD, PhD, FESC; Phone Number: +4535457086; Email: ole.de.backer@regionh.dk
    • Contact: Troels H Jørgensen, MD, PhD; Phone Number: +4535450892; Email: troels.hoejsgaard.joergensen.01@regionh.dk
  • Odense C, Denmark, 5000
    • Not yet recruiting
    • Odense University Hospital
    • Contact: Henrik Nissen; Email: henrik.nissen@rsyd.dk
• Finland
  • Turku, Finland, 20520
    • Not yet recruiting
    • Turku University Hospital
    • Contact: Mikko Savontaus; Email: mikko.savontaus@tyks.fi
• Netherlands
  • Nieuwegein, Netherlands, 3435
    • Not yet recruiting
    • St. Antonius Hospital
    • Contact: Jur ten Berg, MD, PhD; Email: j.ten.berg@antoniusziekenhuis.nl
    • Contact: Christian Overduin, MD, PhD; Email: c.overduin@antoniusziekenhuis.nl
• Norway
  • Oslo, Norway, 0450
    • Not yet recruiting
    • Oslo universitetssygehus
    • Contact: Kristoffer Engh Russell, MD, PhD; Email: krruss@ous-hf.no
• Sweden
  • Gothenburg, Sweden, 413 45
    • Not yet recruiting
    • Sahlgrenska University Hospital
    • Contact: Oskar Angerås, MD, PhD; Email: oskar.angeras@vgregion.se

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Severe symptomatic aortic stenosis patients with an indication for TAVI
• Ability to understand and to comply with the study protocol

Exclusion Criteria:

• Existing indication for oral anticoagulation (e.g., atrial fibrillation, venous thromboembolism, antiphospholipid syndrome, mechanical mitral valve)
• Creatinine clearance <15 mL/min (CKD-EPI formula) or on renal replacement therapy
• Iodine contrast allergy or other condition that prohibits cardiac CT imaging

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: SoC-TAVI; Pre-dilatation and post-dialation optional, as per operator preference. The balloon size used for pre- or post-dilatation is left at the operator's discretion. Operators are only encouraged to post-dilate the implanted transcatheter aortic valve (TAV) in case of ≥ moderate paravalvular regurgitation or a suboptimal transvalvular gradient.	Procedure: SoC-TAVI; During TAVI with either self-expanding or balloon-expandable TAVs: Pre-dilatation: optional, as per operator preference and post-dilatation: optional, as per operator preference. Operators are only encouraged to post-dilate the implanted TAV in case of ≥ moderate paravalvular regurgitation or a suboptimal transvalvular gradient. The balloon size used for pre- or post-dilatation is left at the operator's discretion.
Experimental: OptEx-TAVI; Systematic pre-dilatation and post-dilatation with an optimally-sized balloon	Procedure: OptEx-TAVI; During TAVI with either self-expanding or balloon-expandable TAVs: Pre-dilatation: systematic pre-dilatation with an optimally-sized balloon.; Post-dilatation: systematic TAV post-dilatation with an optimally-sized balloon. Optimally-sized balloon: The recommended balloon size used for pre- and post-dilatation is the perimeter-derived mean diameter of the native aortic annulus minus 1 mm and should never exceed the perimeter-derived mean diameter of the native aortic annulus. A smaller-sized balloon should be considered in case of severe left ventricular outflow tract calcium and/or severely calcified leaflets in combination with a shallow sinus of Valsalva.; In case of post-dilatation of the Evolut TAV (Medtronic, USA), the instructions for use (IFU) for post-dilatation of the Evolut valve should be respected.; Also, a balloon-expandable TAV has to be post-dilated with an optimally-sized balloon in case of randomization to the OptEx-TAVI arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
At least one TAV leaflet with HALT	At least one TAV leaflet with hypoattenuated leaflet thickening (HALT) involving more than the base (≥ 25% of the leaflet curvilinear dimension) as assessed at cardiac CT-scan .	At three months after TAVI

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HALT 50%	At least one TAV leaflet with HALT involving ≥ 50% of the leaflet curvilinear dimension assessed by cardiac CT-scan	At 3 months/At 1 year
HALT 25%	The rate of TAV leaflets with HALT involving ≥ 25% of the leaflet curvilinear dimension assessed by cardiac CT-scan	At 3 months/At 1 year
HALT 50%, multiple	The rate of TAV leaflets with HALT involving ≥ 50% of the leaflet curvilinear dimension assessed by cardiac CT-scan	At 3 months/At 1 year
Bioprosthetic leaflet micro-calcification target-to-background ratio	Ratio of bioprosthetic micro-calcification activity assessed by PET CT- scan by 18F-NaF uptake originating from the valve leaflets observed on 3 orthogonal planes after co-registration of background PET activity with contrast CT angiography. Only for those patients alive at 5 years and volunteering to undergo a F-NaF PET-CT-scan	At 5 years
Valve performance	Intended performance of the valve (mean gradient < 20 mmHg, peak velocity < 3 m/s, Doppler velocity index ≥ 0.25, and less than moderate aortic regurgitation) by TTE as per VARC- 3 criteria	At 3 months/At 1 year
structural valve deterioration	Moderate or greater hemodynamic structural valve deterioration by TTE as per VARC-3 criteria. Only for those patients alive at 5 years and volunteering to undergo a F-NaF PET-CT-scan	At 5 years
Bioprosthetic valve dysfunction (BVD)	Severe bioprosthetic valve dysfunction (BVD) by TTE as per VARC-3 criteria. Only for those patients alive at 5 years and volunteering to undergo a F-NaF PET-CT-scan	At 5 years
Bioprosthetic valve failure (BVF)	As per VARC-3 criteria; Only for those patients alive at 5 years and volunteering to undergo a F-NaF PET-CT-scan	At 5 years
Technical success	As per VARC-3 criteria	Periprocedural
Device success	as per VARC-3 criteria	At 3 months
Early safety	As per VARC-3 criteria	At 3 months
Clinical efficacy	As per VARC-3 criteria	At 1 year
Valve-related long-term clinical efficacy	As per VARC-3 criteria; Only for those patients alive at 5 years and volunteering to undergo a F-NaF PET-CT-scan	At 5 years
Freedom from mortality	Freedom from mortality	Periprocedural, at 3 months and at 1 year
Risk of cardiovascular mortality	Risk of cardiovascular mortality. VARC-3 criteria	At 1 year
Risk of non-cardiovascular mortality	Risk of non-cardiovascular mortality. VARC-3 criteria	At 1 year
Risk of acute kidney injury	Risk of acute kidney injury stage 3 or 4. VARC-3 criteria	At 3 months
Risk of bleeding	Risk of VARC-3 type 2-4 bleeding	At 3 months, 1 year and 5 years (Only for those patients alive at 5 years and volunteering to undergo a F-NaF PET-CT-scan)
Risk of stroke	Risk of all stroke	At 3 months and 1 year
Risk of thomboembolism	Freedom from stroke or peripheral embolism (presumably valve-related, after ruling out other non-valve aetiologies). VARC-3 criteria.	At 5 years
Rate of successful access	Successful access, delivery of the device, and retrieval of the delivery system	Periprocedural
Freedom from surgery or intervention	Rate of freedom from surgery or intervention related to the device or to a major vascular or access-related, or cardiac structural complication	Periprocedural and at 3 months
Risk of vascular complications	Risk of major vascular, access-related, or cardiac structural complication, VARC-3 criteria.	At 3 months
Risk of aortic prosthetic regurgitation	Freedom from moderate or severe aortic regurgitation. VARC-3 criteria	At 3 months
Risk of permanent pacemaker	Risk of new permanent pacemaker due to procedure-related conduction abnormalities	At 3 months
Risk of procedure or valve-related hospitalization	Risk of hospitalization for procedure- or valve-related causes. VARC-3	At 1 year

Collaborators and Investigators

• Sponsor: Ole De Backer
• Investigators: Principal Investigator: Ole De Backer, MD, PhD, FESC, The Heart Center, Rigshospitalet

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2025
• Primary Completion (Estimated): July 1, 2032
• Study Completion (Estimated): July 1, 2033

Study Registration Dates

• First Submitted: June 8, 2025
• First Submitted That Met QC Criteria: June 27, 2025
• First Posted (Actual): June 29, 2025

Study Record Updates

• Last Update Posted (Actual): February 3, 2026
• Last Update Submitted That Met QC Criteria: February 1, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Cardiovascular; TAVI; Aortic stenosis; Transcatheter aortic valve implantation; Valvular heart disease; Transcatheter aortic valve
• Additional Relevant MeSH Terms: Aortic Valve Disease; Cardiovascular Diseases; Heart Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Heart Valve Diseases
• Other Study ID Numbers: OptEx-TAVI Trial; H-25039123 (Other Identifier: Scientific Ethics Committees for the Capital Region of Denmark)

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: No