Aortic Stenosis
Conditions
Brief summary
To compare outcome in patients randomized to treatment with Evolut FX versus 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).
Interventions
DEVICEMedtronic Evolut FX
TAVI performed with Medtronic Evolut FX
DEVICEEdwards Sapien 3 Ultra Resilia
TAVI performed with Edwards Sapien 3 Ultra Resilia
Sponsors
Christian Juhl Terkelsen
Department of Clinical Epidemiology, Aarhus University, DK-8200 Aarhus N, Denmark
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
The patient and operator cannot be blinded to allocated treatment. Most outcomes are registry based and randomization is not anticipated to impact outcome assessment.
Intervention model description
Randomized 1:1
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mortality, stroke, moderate/major aortic regurgitation, moderate/severe THV deterioration | 1-year, 3-year, 5-year, 10-year | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Revascularization (exploratory only) | 30-day, 1-year, 3-year, 5-year, 10-year. | PCI (Percutaneous coronary intervention) CABG (Coronary Artery Bypass Grafting), not scheduled before TAVI |
| Atrial fibrillation (exploratory only) | 30-day, 1-year, 3-year, 5-year, 10-year. | Newly diagnosed atrial fibrillation/flutter |
| TAVI-related complications | 7-days | 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. |
| Proportion with successful implantation of the chosen valve. | 7-days | 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. |
| SMART criteria for bioprosthetic valve dysfunction through 12 months | 1-year | 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. |
| Pacemaker-implantation | 1-year | New pace-maker implantation in pacemaker-naive patients. |
| Vascular and access-related complications (exploratory only) | 30-days | Major vascular access site and access-related complications resulting in endovascular or open surgery using VARC-3 criteria |
| Bleeding and transfusion (exploratory only) | 30-days | 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 |
| Endocarditis (exploratory only) | 30-day, 1-year, 3-year, 5-year, 10-year | According to VARC-3 criteria. |
| Reoperation (exploratory only) | 30-day, 1-year, 3-year, 5-year, 10-year | Transcatheter Aortic Valve Intervention, Surgical Aortic Valve Intervention or Balloon Angioplasty |
| Moderate/severe prosthesis-patient mismatch (exploratory only) | 30-day | 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. |
| Mean gradient (exploratory only) | 30-day, 1-year, 3-year, 5-year, 10-year | Aortic mean gradient, mmHg, as evaluated by Echocardiograpy Core-laboratory. |
| Pacemaker-implantation (exploratory only) | 30-day prior to TAVI, 30-day, 1-year, 3-year, 5-year, 10-year | New pacemaker in pacemaker naive-patients. |
| Readmission for congestive heart failure (exploratory only) | 30-day, 1-year, 3-year, 5-year, 10-year. | Adjudicated. Only monitored until first confirmed case. |
| Kidney injury (exploratory only) | 30-day | 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. |
| AMI (exploratory only) | 30-day, 1-year, 3-year, 5-year, 10-year. | Acute Myocardial Infarction. Adjudicated. Only monitored until first confirmed case. |
Countries
Denmark
Contacts
PRINCIPAL_INVESTIGATORchristian J Terkelsen, Professor
Department of cardiology, Aarhus University Hospital, DK-8200 Aarhus N, Denmark
Outcome results
None listed