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

N/AActive Not RecruitingNCT03112980

Universitätsklinikum Hamburg-Eppendorf1,414 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

1,414

Conditions

Aortic Valve Stenosis

Interventions

Transcatheter aortic valve implantationDEVICE

(TAVI)

Surgical aortic valve replacementPROCEDURE

(SAVR)

Eligibility

Sex: ALLMin age: 65 YearsMax age: 85 Years

Medical Language ↔ Plain English

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

Locations (43)

Outcomes

Primary Outcomes

Freedom from stroke or death

(Efficacy endpoint)

Time frame: within 5 years after randomization

Freedom from stroke or death

(Safety endpoint)

Time frame: within 1 year after randomization

Secondary Outcomes

Freedom from stroke or death

will be assessed at every study visit and compared between TAVI and SAVR groups

Time frame: Five years after last patient in

Overall survival

will be assessed at every study visit and compared between TAVI and SAVR groups

Time frame: Five years after last patient in

Freedom from cardiovascular mortality

will be assessed at every study visit and compared between TAVI and SAVR groups

Time frame: 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

Time frame: Five years after last patient in

Freedom from myocardial infarction

will be assessed at every study visit and compared between TAVI and SAVR groups

Time frame: Five years after last patient in

Freedom from stroke

will be assessed at every study visit and compared between TAVI and SAVR groups

Time frame: Five years after last patient in

Data from ClinicalTrials.gov

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Uniklinik Rheinisch-Westfälische Technische Hochschule Aachen

Aachen, Germany

Universitäts-Herzzentrum Freiburg-Bad Krozingen

Bad Krozingen, Germany

Kerckhoff-Klinik Bad Nauheim

Bad Nauheim, Germany

Herz- und Gefässklinik Bad Neustadt/Saale

Bad Neustadt an der Saale, Germany

Herz- und Diabeteszentrum NRW Bad Oeynhausen

Bad Oeynhausen, Germany

Charité Universitätsmedizin Berlin (Campus Benjamin-Franklin)

Berlin, Germany

Charité Universitätsmedizin Berlin (Campus Mitte)

Berlin, Germany

Charité Universitätsmedizin Berlin (Campus Virchow)

Berlin, Germany

Deutsches Herzzentrum Berlin

Berlin, Germany

Vivantes Friedrichshain

Berlin, Germany

...and 33 more locations

Freedom from major or life-threatening / disabling bleeding

will be assessed at every study visit and compared between TAVI and SAVR groups

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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)

Time frame: 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.

Time frame: 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)

Time frame: 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

Time frame: 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

Time frame: 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).

Time frame: 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.

Time frame: 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).

Time frame: Five years after last patient in

Number of (re) hospitalisations

Number rehospitalisations of all participants. Length of stay in hospital

Time frame: Five years after last patient in