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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Aortic Valve Stenosis

Intervention / Treatment
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* Device: Transcatheter aortic valve implantation
* Procedure: Surgical aortic valve replacement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Heart team consensus that TAVI and SAVR are both medically justified and advisable based on: 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). Patient is symptomatic from his/her aortic valve stenosis New York Heart Association Functional Class ≥ II or Angina pectoris or Syncope. 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). 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. Patient has provided written informed consent to participate in the trial. 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. The patient agrees to undergo SAVR, if randomized to control treatment. The patient and the treating physician agree that the patient will return for all required post-procedure follow-up visits. Patients aged 65 to 85 years. Male patients or females who are postmenopausal defined as no menses for 12 months without an alternative medical cause. Exclusion Criteria: Aortic valve is a congenital unicuspid or congenital bicuspid valve, or is non-calcified Untreated clinically significant coronary artery disease considered a contraindication to an isolated aortic valve procedure (TAVI or SAVR) according to heart team consensus Previous cardiac surgery Any percutaneous coronary intervention performed within 1 month prior to the study procedure Untreated severe mitral or tricuspid regurgitation Untreated severe mitral stenosis Hemodynamic instability requiring inotropic support or mechanical circulatory support Ischemic stroke or intracranial bleeding within 1 month Severe ventricular dysfunction with left ventricular ejection fraction < 20% as measured by resting echocardiogram Hypertrophic obstructive cardiomyopathy or severe basal septal hypertrophy with outflow gradient Echocardiographic evidence of an intracardiac mass, thrombus, vegetation or endocarditis Any other condition considered a contraindication for an isolated aortic valve procedure Symptomatic carotid or vertebral artery disease Expected life expectancy < 12 months due to associated non-cardiac comorbidities Currently participating in another investigational drug or device trial

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transcatheter aortic valve implantation<br>Transcatheter aortic valve implantation (TAVI) using the most appropriate CE (Conformité Européene)-marked device available, with a minimum demand of experience of 30 implanted devices/type per center. | Device: Transcatheter aortic valve implantation<br>* (TAVI)<br>|
| Active Comparator: Surgical aortic valve replacement<br>Surgical aortic valve replacement (SAVR) with free choice of surgical bioprosthesis and free choice of surgical access according to the surgeon's preference. | Procedure: Surgical aortic valve replacement<br>* (SAVR)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom from stroke or death | (Efficacy endpoint) | within 5 years after randomization | 
| Freedom from stroke or death | (Safety endpoint) | within 1 year after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom from stroke or death | will be assessed at every study visit and compared between TAVI and SAVR groups | Five years after last patient in | 
| Overall survival | will be assessed at every study visit and compared between TAVI and SAVR groups | Five years after last patient in | 
| Freedom from cardiovascular mortality | will be assessed at every study visit and compared between TAVI and SAVR groups | Five years after last patient in | 
| Freedom from the composite of all-cause mortality and stroke | will be assessed at every study visit and compared between TAVI and SAVR groups | Five years after last patient in | 
| Freedom from myocardial infarction | will be assessed at every study visit and compared between TAVI and SAVR groups | Five years after last patient in | 
| Freedom from stroke | will be assessed at every study visit and compared between TAVI and SAVR groups | Five years after last patient in | 
| Freedom from major or life-threatening / disabling bleeding | will be assessed at every study visit and compared between TAVI and SAVR groups | Five years after last patient in | 
| Freedom from acute kidney injury | will be assessed at every study visit and compared between TAVI and SAVR groups | Five years after last patient in | 
| Freedom from vascular access site and access-related complications | will be assessed at every study visit and compared between TAVI and SAVR groups | Five years after last patient in | 
| Freedom from conduction disturbances and arrhythmias, need for permanent pacemaker implantation | will be assessed at every study visit and compared between TAVI and SAVR groups | Five years after last patient in | 
| Freedom from residual aortic regurgitation ≥ moderate | will be assessed at every study visit and compared between TAVI and SAVR groups | Five years after last patient in | 
| Composite device success | Number of participants with freedom from procedural mortality and correct positioning of a single transcatheter heart valve (THV) in the proper position with intended performance (no prosthesis- patient mismatch and mean aortic valve gradient <20 mmHg or peak velocity <3 m/s, AND no moderate or severe prosthetic valve regurgitation) | Five years after last patient in | 
| Composite early safety | Number of participants dying and/or number of participants with stroke (disabling and non-disabling), and/or life-threatening bleeding and/or acute kidney injury stages 2/3 and/or coronary artery obstruction requiring Intervention and/or major vascular complication and/or valve-related dysfunction requiring repeat procedure. | within first 30 days after procedure | 
| Composite clinical efficacy | Number or participants dying and/or number of participants with stroke (disabling and non-disabling) and/or rehospitalisation for worsening heart failure or valve-related symptoms and/or New York Heart Association functional class (NYHA) III or IV and/or valve-related dysfunction (mean aortic valve gradient >20 mmHg, effective orifice area (EOA) <0.9-1.1 cm2 and/or Doppler Velocity Index (DVI) <0. 35 m/s, AND/OR moderate or severe prosthetic valve regurgitation) | within first 30 days after procedure | 
| Freedom from prosthetic valve dysfunction | will be assessed at every study visit and compared between TAVI and SAVR groups | Five years after last patient in | 
| Freedom from prosthetic aortic valve endocarditis | will be assessed at every study visit and compared between TAVI and SAVR groups | Five years after last patient in | 
| Freedom from the composite time-related valve safety | Number of participants with structural valve deterioration (including repeat procedures, prosthetic valve endocarditis and/or thrombosis) and/or number of participants with thromboembolic events (stroke) and/or Valve Academic Research Consortium (VARC-2) bleeding (unless clearly unrelated to valve therapy). | Five years after last patient in | 
| Quality of life measures | Number of participants with reduced quality of life measures after valve replacement as compared to baseline levels prior to valve-replacement, assessed using EuroQol five dimensions (EQ-5D) questionnaire and/or Barthel Index and/or center for epidemiologic studies depression (CES-D) Scale. | Five years after last patient in | 
| Health economic analysis | Incremental cost-effectiveness of TAVI compared to surgical valve replacement, by using quality adjusted life years (QALYs). | Five years after last patient in | 
| Number of (re) hospitalisations | Number rehospitalisations of all participants. Length of stay in hospital | Five years after last patient in | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aortic Valve Stenosis, Transcatheter Aortic Valve Replacement, Surgical aortic valve replacement, Low to intermediate operative risk