Randomized Trial of TAVI vs. SAVR in Patients With Severe Aortic Valve Stenosis at Low to Intermediate Risk of Mortality

Randomized, Multi-Center, Event-Driven Trial of TAVI Versus SAVR in Patients With Symptomatic Severe Aortic Valve Stenosis and Intermediate Risk of Mortality, as Assessed by STS-Score - DEDICATE

Randomized controlled, multi-center trial randomizing patients with symptomatic severe aortic stenosis at low to intermediate operative risk of mortality in a 1:1 fashion to transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR) to test, whether TAVI is non-inferior to SAVR, as measured by all-cause mortality or stroke after 1 and 5 years.

A paradigm-shift towards performing TAVI in intermediate- and low-risk patients has already begun, as procedural results of TAVI have improved significantly within the past years. Nevertheless, a prospective and independent comparison of surgical (SAVR) and interventional (TAVI) valve therapy in patients considered at low to intermediate risk that covers an "all-comers" patient population and multiple devices has not yet been performed.

The DEDICATE-trial is designed as a prospectively randomized (1:1), multi-center, comparator-controlled interventional trial to investigate whether transcatheter aortic valve implantation (TAVI) is non-inferior - as measured by all-cause mortality or stroke after 1 and 5 years - compared to surgical aortic valve replacement (SAVR) in the treatment of patients with symptomatic severe aortic stenosis at low to intermediate operative risk of mortality, as assessed by the local Heart Team.

Inclusion Criteria:

1. Heart team consensus that TAVI and SAVR are both medically justified and advisable based on:

   1. Degenerative aortic valve stenosis with echocardiographically derived criteria:

      • Mean gradient >40 mmHg or
      • Jet velocity greater than 4.0 m/s or
      • Aortic valve area (AVA) of < 1.0 cm2 (indexed effective orifice area < 0.6cm2/m2).

   2. Patient is symptomatic from his/her aortic valve stenosis

      • New York Heart Association Functional Class ≥ II or
      • Angina pectoris or
      • Syncope.

   3. Patient is classified as low to intermediate operative risk as assessed by the local heart team according to the variables outlined in the 2017 ESC/EACTS Guidelines for the Management of valvular heart disease, taking into account cardiac and extracardiac Patient characteristics and established risk scores (e.g. STS-PROM, EuroSCORE).

   4. A transfemoral or alternative (e.g. transapical, transaortic, transaxillary) access for TAVI seems feasible. Centers should follow a "transfemoral first" strategy for the primary route of access; however, other routes of access are also allowed, as decided by local heart team consensus.

2. Patient has provided written informed consent to participate in the trial.

3. Ability of the patient to understand the patient information and to personally sign and date the informed consent to participate in the study, before performing any study related procedures.

4. The patient agrees to undergo SAVR, if randomized to control treatment.

5. The patient and the treating physician agree that the patient will return for all required post-procedure follow-up visits.

6. Patients aged 65 to 85 years.

7. Male patients or females who are postmenopausal defined as no menses for 12 months without an alternative medical cause.

Exclusion Criteria:

1. Aortic valve is a congenital unicuspid or congenital bicuspid valve, or is non-calcified
2. Untreated clinically significant coronary artery disease considered a contraindication to an isolated aortic valve procedure (TAVI or SAVR) according to heart team consensus
3. Previous cardiac surgery
4. Any percutaneous coronary intervention performed within 1 month prior to the study procedure
5. Untreated severe mitral or tricuspid regurgitation
6. Untreated severe mitral stenosis
7. Hemodynamic instability requiring inotropic support or mechanical circulatory support
8. Ischemic stroke or intracranial bleeding within 1 month
9. Severe ventricular dysfunction with left ventricular ejection fraction < 20% as measured by resting echocardiogram
10. Hypertrophic obstructive cardiomyopathy or severe basal septal hypertrophy with outflow gradient
11. Echocardiographic evidence of an intracardiac mass, thrombus, vegetation or endocarditis
12. Any other condition considered a contraindication for an isolated aortic valve procedure
13. Symptomatic carotid or vertebral artery disease
14. Expected life expectancy < 12 months due to associated non-cardiac comorbidities
15. Currently participating in another investigational drug or device trial