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

Sponsor

Universitätsklinikum Hamburg-Eppendorf (Other)

Overall Status

Recruiting

CT.gov ID

NCT03112980

Collaborator

Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK) (Other), Deutsche Herzstiftung e.V. (Other)

1,404

Enrollment

Locations

Arms

117.7

Anticipated Duration (Months)

32.7

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Aortic Valve Stenosis	Device: Transcatheter aortic valve implantation Procedure: Surgical aortic valve replacement	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

1404 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

May 10, 2017

Anticipated Primary Completion Date :

Mar 1, 2027

Anticipated Study Completion Date :

Mar 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Device: Transcatheter aortic valve implantation (TAVI)
Active Comparator: 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.	Procedure: Surgical aortic valve replacement (SAVR)

Arm

Intervention/Treatment

Experimental: 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.

Device: Transcatheter aortic valve implantation

(TAVI)

Active Comparator: 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.

Procedure: Surgical aortic valve replacement

(SAVR)

Outcome Measures

Primary Outcome Measures

Freedom from stroke or death [within 5 years after randomization]
(Efficacy endpoint)
Freedom from stroke or death [within 1 year after randomization]
(Safety endpoint)

Secondary Outcome Measures

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 cardiovascular mortality [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 myocardial infarction [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 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 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 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 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
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
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 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.
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 valve dysfunction [Five years after last patient in]
will be assessed at every study visit and compared between TAVI and SAVR groups
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).
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.
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).
Number of (re) hospitalisations [Five years after last patient in]
Number rehospitalisations of all participants. Length of stay in hospital

Eligibility Criteria

Criteria

Ages Eligible for Study:

65 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Uniklinik Rheinisch-Westfälische Technische Hochschule Aachen	Aachen	Germany
2	Universitäts-Herzzentrum Freiburg-Bad Krozingen	Bad Krozingen	Germany
3	Kerckhoff-Klinik Bad Nauheim	Bad Nauheim	Germany
4	Herz- und Gefässklinik Bad Neustadt/Saale	Bad Neustadt an der Saale	Germany
5	Herz- und Diabeteszentrum NRW Bad Oeynhausen	Bad Oeynhausen	Germany
6	Charité Universitätsmedizin Berlin (Campus Benjamin-Franklin)	Berlin	Germany
7	Charité Universitätsmedizin Berlin (Campus Mitte)	Berlin	Germany
8	Charité Universitätsmedizin Berlin (Campus Virchow)	Berlin	Germany
9	Deutsches Herzzentrum Berlin	Berlin	Germany
10	Vivantes Friedrichshain	Berlin	Germany
11	Vivantes Humboldt Kliniken	Berlin	Germany
12	Vivantes Klinikum am Urban	Berlin	Germany
13	Vivantes Neukölln	Berlin	Germany
14	Immanuel Klinikum Bernau	Bernau	Germany	16321
15	Kliniken der Ruhr-Universität Bochum	Bochum	Germany
16	Medizinische Hochschule Brandenburg Theodor Fontane	Brandenburg an der Havel	Germany
17	Herzzentrum Dresden an der Technischen Universität Dresden	Dresden	Germany
18	Universitätsklinikum Düsseldorf	Düsseldorf	Germany
19	Universitätsklinikum Erlangen	Erlangen	Germany
20	Universitätsklinikum Essen, Klinikum für Kardiologie und Angiologie am Westdeutschen Herz- und Gefäßzentrum	Essen	Germany
21	Universitätsklinikum Frankfurt	Frankfurt	Germany
22	Universitäts-Herzzentrum Freiburg-Bad Krozingen	Freiburg	Germany
23	Universitätsklinikum Giessen und Marburg	Giessen	Germany
24	Universitätsmedizin Greifswald / Klinikum Karlsburg	Greifswald / Karlsburg	Germany
25	Universitätsklinikum Göttingen	Göttingen	Germany
26	Universitätsklinikum Halle (Saale)	Halle (Saale)	Germany
27	Universitäres Herz- und Gefäßzentrum Hamburg (UHZ)	Hamburg	Germany	20251
28	Medizinische Hochschule Hannover	Hannover	Germany
29	Universitätsklinikum Heidelberg	Heidelberg	Germany
30	Universitätsklinikum Jena	Jena	Germany
31	Universitätsklinikum Schleswig-Holstein	Kiel	Germany
32	Bundeswehrzentralkrankenhaus Koblenz	Koblenz	Germany	56076
33	Herzzentrum der Uniklinik Köln	Köln	Germany
34	Deutsches Herzzentrum Leipzig	Leipzig	Germany
35	Universitäres Herzzentrum Lübeck	Lübeck	Germany
36	Otto-von Guericke-Universität Magdeburg	Magdeburg	Germany
37	Universitätsmedizin Mainz	Mainz	Germany
38	Deutsches Herzzentrum München	München	Germany
39	LMU Klinikum der Universität München	München	Germany
40	Universitätsklinikum Münster	Münster	Germany
41	Universitätsklinikum Regensburg	Regensburg	Germany
42	Robert Bosch Krankenhaus	Stuttgart	Germany
43	Universitätsklinikum Ulm	Ulm	Germany

Sponsors and Collaborators

Universitätsklinikum Hamburg-Eppendorf
Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)
Deutsche Herzstiftung e.V.

Investigators

Principal Investigator: Stefan Blankenberg, MD, Universitäres Herz- und Gefäßzentrum Hamburg (UHZ), Germany
Principal Investigator: Jochen Cremer, MD, Universitätsklinikum Schleswig-Holstein, Germany