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

Not Applicable

Active, not recruiting

• Conditions: Aortic Valve Stenosis
• Interventions: Procedure: Surgical aortic valve replacement; Device: Transcatheter aortic valve implantation

• Registration Number: NCT03112980
• Lead Sponsor: Universitätsklinikum Hamburg-Eppendorf

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2017-03-21
• Study First Submitted QC: 2017-04-07
• Study First Posted: 2017-04-13
• Study Start: 2017-05-10
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-25
• Last Update Posted: 2024-04-26
• Primary Completion: 2028-01
• Study Completion: 2028-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 1414

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Surgical aortic valve replacement	Surgical aortic valve replacement	Surgical aortic valve replacement (SAVR) with free choice of surgical bioprosthesis and free choice of surgical access according to the surgeon's preference.
Transcatheter aortic valve implantation	Transcatheter aortic valve implantation	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.

Primary Outcome Measures

Name	Time	Method
Freedom from stroke or death	within 1 year after randomization	(Safety endpoint)

Secondary Outcome Measures

Name	Time	Method
Freedom from cardiovascular mortality	Five years after last patient in	will be assessed at every study visit and compared between TAVI and SAVR groups
Freedom from stroke	Five years after last patient in	will be assessed at every study visit and compared between TAVI and SAVR groups
Freedom from acute kidney injury	Five years after last patient in	will be assessed at every study visit and compared between TAVI and SAVR groups
Freedom from the composite of all-cause mortality and stroke	Five years after last patient in	will be assessed at every study visit and compared between TAVI and SAVR groups
Freedom from vascular access site and access-related complications	Five years after last patient in	will be assessed at every study visit and compared between TAVI and SAVR groups
Freedom from residual aortic regurgitation ≥ moderate	Five years after last patient in	will be assessed at every study visit and compared between TAVI and SAVR groups
Freedom from stroke or death	Five years after last patient in	will be assessed at every study visit and compared between TAVI and SAVR groups
Overall survival	Five years after last patient in	will be assessed at every study visit and compared between TAVI and SAVR groups
Freedom from myocardial infarction	Five years after last patient in	will be assessed at every study visit and compared between TAVI and SAVR groups
Freedom from major or life-threatening / disabling bleeding	Five years after last patient in	will be assessed at every study visit and compared between TAVI and SAVR groups
Freedom from conduction disturbances and arrhythmias, need for permanent pacemaker implantation	Five years after last patient in	will be assessed at every study visit and compared between TAVI and SAVR groups
Composite device success	Five years after last patient in	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)
Composite clinical efficacy	within first 30 days after procedure	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)
Freedom from prosthetic aortic valve endocarditis	Five years after last patient in	will be assessed at every study visit and compared between TAVI and SAVR groups
Freedom from the composite time-related valve safety	Five years after last patient in	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).
Number of (re) hospitalisations	Five years after last patient in	Number rehospitalisations of all participants. Length of stay in hospital
Composite early safety	within first 30 days after procedure	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.
Freedom from prosthetic valve dysfunction	Five years after last patient in	will be assessed at every study visit and compared between TAVI and SAVR groups
Health economic analysis	Five years after last patient in	Incremental cost-effectiveness of TAVI compared to surgical valve replacement, by using quality adjusted life years (QALYs).
Quality of life measures	Five years after last patient in	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.

Trial Locations

Locations (42)

Deutsches Herzzentrum Berlin; 🇩🇪 Berlin, Germany

Vivantes Humboldt Kliniken; 🇩🇪 Berlin, Germany

Herz- und Diabeteszentrum NRW Bad Oeynhausen; 🇩🇪 Bad Oeynhausen, Germany

Uniklinik Rheinisch-Westfälische Technische Hochschule Aachen; 🇩🇪 Aachen, Germany

Charité Universitätsmedizin Berlin (Campus Mitte); 🇩🇪 Berlin, Germany

Universitäres Herz- und Gefäßzentrum Hamburg (UHZ); 🇩🇪 Hamburg, Germany

Universitätsklinikum Halle (Saale); 🇩🇪 Halle (Saale), Germany

Herzzentrum der Uniklinik Köln; 🇩🇪 Köln, Germany

Deutsches Herzzentrum München; 🇩🇪 München, Germany

Universitätsklinikum Schleswig-Holstein; 🇩🇪 Kiel, Germany

Universitäts-Herzzentrum Freiburg-Bad Krozingen; 🇩🇪 Freiburg, Germany

Medizinische Hochschule Brandenburg Theodor Fontane; 🇩🇪 Brandenburg an der Havel, Germany

Universitätsklinikum Göttingen; 🇩🇪 Göttingen, Germany

Robert Bosch Krankenhaus; 🇩🇪 Stuttgart, Germany

Kliniken der Ruhr-Universität Bochum; 🇩🇪 Bochum, Germany

Medizinische Hochschule Hannover; 🇩🇪 Hannover, Germany

Universitäres Herzzentrum Lübeck; 🇩🇪 Lübeck, Germany

Universitätsklinikum Ulm; 🇩🇪 Ulm, Germany

Herz- und Gefässklinik Bad Neustadt/Saale; 🇩🇪 Bad Neustadt an der Saale, Germany

Charité Universitätsmedizin Berlin (Campus Benjamin-Franklin); 🇩🇪 Berlin, Germany

Vivantes Friedrichshain; 🇩🇪 Berlin, Germany

Universitätsklinikum Erlangen; 🇩🇪 Erlangen, Germany

Universitätsklinikum Giessen und Marburg; 🇩🇪 Giessen, Germany

Universitätsmedizin Greifswald / Klinikum Karlsburg; 🇩🇪 Greifswald / Karlsburg, Germany

Universitätsklinikum Jena; 🇩🇪 Jena, Germany

Universitätsklinikum Heidelberg; 🇩🇪 Heidelberg, Germany

Universitätsmedizin Mainz; 🇩🇪 Mainz, Germany

Kerckhoff-Klinik Bad Nauheim; 🇩🇪 Bad Nauheim, Germany

Charité Universitätsmedizin Berlin (Campus Virchow); 🇩🇪 Berlin, Germany

Vivantes Klinikum am Urban; 🇩🇪 Berlin, Germany

Vivantes Neukölln; 🇩🇪 Berlin, Germany

Immanuel Klinikum Bernau; 🇩🇪 Bernau, Germany

Herzzentrum Dresden an der Technischen Universität Dresden; 🇩🇪 Dresden, Germany

Universitätsklinikum Frankfurt; 🇩🇪 Frankfurt, Germany

Universitätsklinikum Düsseldorf; 🇩🇪 Düsseldorf, Germany

Universitätsklinikum Essen, Klinikum für Kardiologie und Angiologie am Westdeutschen Herz- und Gefäßzentrum; 🇩🇪 Essen, Germany

Bundeswehrzentralkrankenhaus Koblenz; 🇩🇪 Koblenz, Germany

Deutsches Herzzentrum Leipzig; 🇩🇪 Leipzig, Germany

LMU Klinikum der Universität München; 🇩🇪 München, Germany

Universitätsklinikum Münster; 🇩🇪 Münster, Germany

Universitätsklinikum Regensburg; 🇩🇪 Regensburg, Germany

Otto-von Guericke-Universität Magdeburg; 🇩🇪 Magdeburg, Germany