Clinical trial NCT03112980: Randomized Trial of TAVI vs. SAVR in Patients With Severe Aortic Valve Stenosis at Low to Intermediate Risk of Mortality
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Aortic Valve Stenosis
Keywords: Aortic Valve Stenosis
Transcatheter Aortic Valve Replacement
Surgical aortic valve replacement
Low to intermediate operative risk
Lead sponsor: Universitätsklinikum Hamburg-Eppendorf
Sponsor class: OTHER
Collaborators: name: Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)
name: The German Heart Foundation
First posted: 2017-04-13
Enrollment: 1414
Sex: ALL
Minimum age (years): 65
Maximum age (years): 85
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Freedom from stroke or death
timeFrame: within 5 years after randomization
measure: Freedom from stroke or death
timeFrame: within 1 year after randomization
Secondary outcomes:
measure: Freedom from stroke or death
timeFrame: Five years after last patient in
measure: Overall survival
timeFrame: Five years after last patient in
measure: Freedom from cardiovascular mortality
timeFrame: Five years after last patient in
measure: Freedom from the composite of all-cause mortality and stroke
timeFrame: Five years after last patient in
measure: Freedom from myocardial infarction
timeFrame: Five years after last patient in
measure: Freedom from stroke
timeFrame: Five years after last patient in
measure: Freedom from major or life-threatening / disabling bleeding
timeFrame: Five years after last patient in
measure: Freedom from acute kidney injury
timeFrame: Five years after last patient in
measure: Freedom from vascular access site and access-related complications
timeFrame: Five years after last patient in
measure: Freedom from conduction disturbances and arrhythmias, need for permanent pacemaker implantation
timeFrame: Five years after last patient in
measure: Freedom from residual aortic regurgitation ≥ moderate
timeFrame: Five years after last patient in
measure: Composite device success
timeFrame: Five years after last patient in
measure: Composite early safety
timeFrame: within first 30 days after procedure
measure: Composite clinical efficacy
timeFrame: within first 30 days after procedure
measure: Freedom from prosthetic valve dysfunction
timeFrame: Five years after last patient in
measure: Freedom from prosthetic aortic valve endocarditis
timeFrame: Five years after last patient in
measure: Freedom from the composite time-related valve safety
timeFrame: Five years after last patient in
measure: Quality of life measures
timeFrame: Five years after last patient in
measure: Health economic analysis
timeFrame: Five years after last patient in
measure: Number of (re) hospitalisations
timeFrame: Five years after last patient in
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: Uniklinik Rheinisch-Westfälische Technische Hochschule Aachen
city: Bad Krozingen
country: Germany
facility: Universitäts-Herzzentrum Freiburg-Bad Krozingen
city: Bad Nauheim
country: Germany
facility: Kerckhoff-Klinik Bad Nauheim
city: Bad Neustadt an der Saale
country: Germany
facility: Herz- und Gefässklinik Bad Neustadt/Saale
city: Bad Oeynhausen
country: Germany
facility: Herz- und Diabeteszentrum NRW Bad Oeynhausen
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin (Campus Benjamin-Franklin)
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin (Campus Mitte)
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin (Campus Virchow)
city: Berlin
country: Germany
facility: Deutsches Herzzentrum Berlin
city: Berlin
country: Germany
facility: Vivantes Friedrichshain
city: Berlin
country: Germany
facility: Vivantes Humboldt Kliniken
city: Berlin
country: Germany
facility: Vivantes Klinikum am Urban
city: Berlin
country: Germany
facility: Vivantes Neukölln
city: Bernau
country: Germany
facility: Immanuel Klinikum Bernau
city: Bochum
country: Germany
facility: Kliniken der Ruhr-Universität Bochum
city: Brandenburg an der Havel
country: Germany
facility: Medizinische Hochschule Brandenburg Theodor Fontane
city: Dresden
country: Germany
facility: Herzzentrum Dresden an der Technischen Universität Dresden
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
city: Essen
country: Germany
facility: Universitätsklinikum Essen, Klinikum für Kardiologie und Angiologie am Westdeutschen Herz- und Gefäßzentrum
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt
city: Freiburg
country: Germany
facility: Universitäts-Herzzentrum Freiburg-Bad Krozingen
city: Giessen
country: Germany
facility: Universitätsklinikum Giessen und Marburg
city: Greifswald / Karlsburg
country: Germany
facility: Universitätsmedizin Greifswald / Klinikum Karlsburg
city: Göttingen
country: Germany
facility: Universitätsklinikum Göttingen
city: Halle (Saale)
country: Germany
facility: Universitätsklinikum Halle (Saale)
city: Hamburg
country: Germany
facility: Universitäres Herz- und Gefäßzentrum Hamburg (UHZ)
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Jena
country: Germany
facility: Universitätsklinikum Jena
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
city: Koblenz
country: Germany
facility: Bundeswehrzentralkrankenhaus Koblenz
city: Köln
country: Germany
facility: Herzzentrum der Uniklinik Köln
city: Leipzig
country: Germany
facility: Deutsches Herzzentrum Leipzig
city: Lübeck
country: Germany
facility: Universitäres Herzzentrum Lübeck
city: Magdeburg
country: Germany
facility: Otto-von Guericke-Universität Magdeburg
city: Mainz
country: Germany
facility: Universitätsmedizin Mainz
city: München
country: Germany
facility: Deutsches Herzzentrum München
city: München
country: Germany
facility: LMU Klinikum der Universität München
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg
city: Stuttgart
country: Germany
facility: Robert Bosch Krankenhaus
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
Study officials:
affiliation: Universitäres Herz- und Gefäßzentrum Hamburg (UHZ), Germany
name: Stefan Blankenberg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitätsklinikum Schleswig-Holstein, Germany
name: Jochen Cremer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Seiffert M, Vonthein R, Baumgartner H, Borger MA, Choi YH, Falk V, Frey N, Hagendorff A, Hagl C, Hamm C, Konig IR, Landmesser U, Massberg S, Reichenspurner H, Thiele H, Twerenbold R, Vens M, Walther T, Ziegler A, Cremer J, Blankenberg S. Transcatheter aortic valve implantation versus surgical aortic valve replacement in patients at low to intermediate surgical risk: rationale and design of the randomised DEDICATE Trial. EuroIntervention. 2023 Oct 23;19(8):652-658. doi: 10.4244/EIJ-D-23-00232.
citation: Blankenberg S, Seiffert M, Vonthein R, Baumgartner H, Bleiziffer S, Borger MA, Choi YH, Clemmensen P, Cremer J, Czerny M, Diercks N, Eitel I, Ensminger S, Frank D, Frey N, Hagendorff A, Hagl C, Hamm C, Kappert U, Karck M, Kim WK, Konig IR, Krane M, Landmesser U, Linke A, Maier LS, Massberg S, Neumann FJ, Reichenspurner H, Rudolph TK, Schmid C, Thiele H, Twerenbold R, Walther T, Westermann D, Xhepa E, Ziegler A, Falk V; DEDICATE-DZHK6 Trial Investigators. Transcatheter or Surgical Treatment of Aortic-Valve Stenosis. N Engl J Med. 2024 May 2;390(17):1572-1583. doi: 10.1056/NEJMoa2400685. Epub 2024 Apr 8.