Aortic Stenosis Disease, Valvular Heart Disease
Conditions
Keywords
Aortic stenosis, Cardiovascular, Transcatheter aortic valve, Transcatheter aortic valve implantation, Valvular heart disease, TAVI
Brief summary
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.
Detailed description
A total of 1010 patients will be included in the OptEx-TAVI trial and randomised 1:1 to either : * SoC-TAVI (N = 505) or * OptEx-TAVI (N = 505) 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 native aortic valve stenosis * 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
Interventions
PROCEDUREOptEx-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: 1. 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. 2. 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. 3. Also, a balloon-expandable TAV has to be post-dilated with an optimally-sized balloon in case of randomization to the OptEx-TAVI arm.
PROCEDURESoC-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.
Sponsors
Ole De Backer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Severe native aortic valve stenosis * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| At least one TAV leaflet with HALT | At three months after TAVI | 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 . |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HALT 50% | At 3 months/At 1 year | At least one TAV leaflet with HALT involving ≥ 50% of the leaflet curvilinear dimension assessed by cardiac CT-scan |
| HALT 25% | At 3 months/At 1 year | The rate of TAV leaflets with HALT involving ≥ 25% of the leaflet curvilinear dimension assessed by cardiac CT-scan |
| HALT 50%, multiple | At 3 months/At 1 year | The rate of TAV leaflets with HALT involving ≥ 50% of the leaflet curvilinear dimension assessed by cardiac CT-scan |
| Bioprosthetic leaflet micro-calcification target-to-background ratio | At 5 years | 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 |
| Valve performance | At 3 months/At 1 year | 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 |
| structural valve deterioration | At 5 years | 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 |
| Bioprosthetic valve dysfunction (BVD) | At 5 years | 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 |
| Bioprosthetic valve failure (BVF) | At 5 years | As per VARC-3 criteria; Only for those patients alive at 5 years and volunteering to undergo a F-NaF PET-CT-scan |
| Technical success | Periprocedural | As per VARC-3 criteria |
| Device success | At 3 months | as per VARC-3 criteria |
| Early safety | At 3 months | As per VARC-3 criteria |
| Clinical efficacy | At 1 year | As per VARC-3 criteria |
| Valve-related long-term clinical efficacy | At 5 years | As per VARC-3 criteria; Only for those patients alive at 5 years and volunteering to undergo a F-NaF PET-CT-scan |
| Freedom from mortality | Periprocedural, at 3 months and at 1 year | Freedom from mortality |
| Risk of cardiovascular mortality | At 1 year | Risk of cardiovascular mortality. VARC-3 criteria |
| Risk of non-cardiovascular mortality | At 1 year | Risk of non-cardiovascular mortality. VARC-3 criteria |
| Risk of acute kidney injury | At 3 months | Risk of acute kidney injury stage 3 or 4. VARC-3 criteria |
| Risk of 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 VARC-3 type 2-4 bleeding |
| Risk of stroke | At 3 months and 1 year | Risk of all stroke |
| Risk of thomboembolism | At 5 years | Freedom from stroke or peripheral embolism (presumably valve-related, after ruling out other non-valve aetiologies). VARC-3 criteria. |
| Rate of successful access | Periprocedural | Successful access, delivery of the device, and retrieval of the delivery system |
| Freedom from surgery or intervention | Periprocedural and at 3 months | Rate of freedom from surgery or intervention related to the device or to a major vascular or access-related, or cardiac structural complication |
| Risk of vascular complications | At 3 months | Risk of major vascular, access-related, or cardiac structural complication, VARC-3 criteria. |
| Risk of aortic prosthetic regurgitation | At 3 months | Freedom from moderate or severe aortic regurgitation. VARC-3 criteria |
| Risk of permanent pacemaker | At 3 months | Risk of new permanent pacemaker due to procedure-related conduction abnormalities |
| Risk of procedure or valve-related hospitalization | At 1 year | Risk of hospitalization for procedure- or valve-related causes. VARC-3 |
Countries
Belgium, Denmark, Finland, Netherlands, Norway, Sweden
Contacts
CONTACTOle De Backer, MD, PhD, FESC
CONTACTTroels H Jørgensen, MD, PhD
PRINCIPAL_INVESTIGATOROle De Backer, MD, PhD, FESC
The Heart Center, Rigshospitalet
Outcome results
None listed