Aortic Valve Stenosis, Cardiovascular Diseases, Heart Diseases, Heart Valve Diseases, Ventricular Outflow Obstruction
Conditions
Keywords
heart valve disease, valvular bioprosthesis, aortic valve replacement, Randomized clinical trial
Brief summary
A randomized clinical trial investigating transcatheter (TAVR) versus surgical (SAVR) aortic valve replacement in patients 75 years of age or younger suffering from severe aortic valve stenosis. Study hypothesis: The clinical outcome (death of any cause, stroke and rehospitalization (related to the procedure, valve or heart failure)) obtained within one year after TAVR is non-inferior to SAVR.
Detailed description
BACKGROUND: Acquired aortic valve stenosis (AS) is the most common heart valve disease in the Western World with a prevalence of 2-7% at the age of \>65 years. If untreated, it may lead to heart failure and death. Surgical aortic valve replacement (SAVR) until recent years has been the definitive treatment for patients with severe symptomatic AS. A less invasive transcatheter aortic valve replacement (TAVR) has been developed and has been a treatment of choice mostly for elderly high risk or inoperable patients. As TAVR technology is continuously evolving and improving, it may be anticipated that it will become a valuable alternative - and even the preferred choice of treatment - for younger, low-risk patients with severe aortic valve stenosis in the near future. However, to date, there is no clinical evidence that supports this hypothesis. AIM: The purpose of the study is to compare TAVR and SAVR with regard to the intra- and post-procedural morbidity and mortality rate, hospitalization length, functional capacity, quality of life, and valvular prosthesis function in younger, low risk patients with severe bicuspid or tricuspid AS, scheduled for aortic valve replacement. POPULATION: Younger low risk patients with severe aortic valve stenosis, which are scheduled for aortic valve replacement using a bioprosthesis. Subjects fulfilling the inclusion criteria, not having any exclusion criteria, and consenting to the trial will be randomized 1:1 to TAVR or SAVR with 186 patients in each group. DESIGN: The study is a randomized clinical multicenter trial. Central randomization with variable block size and stratification by gender and coronary comorbidity will be used. An independent event committee blinded to treatment allocation will adjudicate safety endpoints. INTERVENTIONS: TAVR: Any CE-Mark approved transcatheter aortic bioprosthesis may be used in the study, and the choice is at the discretion of the local TAVR team. The transfemoral TAVR procedure may be performed under general anaesthesia, local anaesthesia/conscious sedation, or local anesthesia. Percutaneous coronary intervention (PCI) can be performed up to 30 days prior to TAVR or as a hybrid procedure. SAVR: The surgical SAVR technique follows standard protocol of the local department of cardio-thoracic surgery. The operation is performed under general anesthesia, which follows standard protocol of the department of anesthesiology. A commercial available surgical aortic bioprosthesis at the surgeons discretion will be implanted. Concomitant coronary artery bypass graft (CABG) surgery may be performed. END POINTS: The primary endpoint is the composite rate of death of any cause, stroke and rehospitalization (related to the procedure, valve or heart failure) within one year after the procedure. Secondary endpoints are listed below. Follow-up will be performed after 1 and 12 months and yearly thereafter for a minimum of 10 years.
Interventions
DEVICETranscatheter aortic valve replacement
Retrograde transfemoral transcatheter aortic valve replacement with any CE mark approved aortic bioprosthesis with or without concomitant percutaneous coronary intervention.
Conventional surgical aortic valve replacement with a bioprosthesis using normothermic cardiopulmonary bypass and cold blood cardioplegia cardiac arrest with or without concomitant coronary artery bypass graft surgery.
Sponsors
Symetis SA
Boston Scientific Corporation
Abbott
Edwards Lifesciences
Ole De Backer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age 75 years or younger. * Severe calcific AS (Valve area \<1cm2 (or \<0.6 cm2/m2) AND one of the two following criteria: mean gradient \>40mmHg or peak jet velocity \>4.0m/s, OR in presence of low flow, low gradient with reduced or normal LVEF\<50%, a dobutamine stress echo should verify true severe AS rather than pseudo-AS * Symptomatic with angina pectoris, dyspnea or exercise-induced syncope or near syncope OR asymptomatic with abnormal exercise test showing symptoms on exercise clearly related to AS or systolic LV dysfunction (LVEF \<50%) not due to another cause. * Anticipated usage of biological aortic valve prosthesis. * Low risk for conventional surgery (STS Score \<4%). * Suitable for both SAVR and transfemoral TAVR. * Life expectancy \>1 year after the intervention. * Informed consent to participate in the study after adequate information about the study before randomization and intervention.
Exclusion criteria
* Coronary artery disease, not suitable for both percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG). * Coronary angiogram with a SYNTAX-score \>22. * LVEF \<25% without contractile reserve during dobutamine stress echocardiography. * Porcelain aorta, which prevents open-heart surgery. * Bicuspid valve with aorta ascendens diameter ≥45mm * Severe femoral, iliac or aortic atherosclerosis, calcification, coarctation, aneurysm or tortuosity, which prevents transfemoral TAVR. * Need for open heart surgery other than SAVR with or without CABG. * Myocardial infarction within last 30 days * Stroke or TIA within the last 30 days. NOTION-2, 01. February 2017, version 5 9 * Current endocarditis, intracardiac tumor, thrombus or vegetation. * Ongoing severe infection requiring intravenous antibiotics. * Unstable pre-procedural condition requiring intravenous inotropes or mechanical assist device (IABP, Impella) on the day of intervention. * Kidney disease requiring dialysis or severely impaired lung function (FEV1 and/or diffusion capacity \<40% of predicted). * Allergy to heparin, iodid contrast agent, warfarin, aspirin or clopidogrel.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite rate of all-cause mortality, stroke and rehospitalization (related to the procedure, the valve or heart failure) within one year after the procedure. | at one year post-procedural. | VARC-3 definitions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Procedure time | Intraoperative | hours |
| Duration of index hospitalization | Number of days from admission to discharge (expected an averge of 7 days) | days |
| Composite rate of all-cause mortality, stroke and rehospitalization (related to the procedure, the valve or heart failure) | at 1 month and yearly thereafter up to 10 years post-procedure | VARC-3 definitions |
| Composite rate of all-cause mortality, disabling stroke and rehospitalization (related to the procedure, the valve or heart failure) | at 1 and 12 months, and yearly thereafter up to 10 years post-procedure | VARC-3 definitions |
| Rehospitalization both composite and individual of related to the procedure, the valve or heart failure) | at 1 and 12 months, and yearly thereafter up to 10 years post-procedure | VARC-3 definitions |
| Composite rate of all-cause mortality and disabling stroke | at 1 and 12 months, and yearly thereafter up to 10 years post-procedure | VARC-3 definitions |
| All-cause mortality | at 1 and 12 months, and yearly thereafter up to 10 years post-procedure | VARC-3 definitions |
| Non-cardiovascular mortality | at 1 and 12 months, and yearly thereafter up to 10 years post-procedure | VARC-3 definitions |
| Stroke | at 1 and 12 months, and yearly thereafter up to 10 years post-procedure | VARC-3 definitions |
| Disabling Stroke | at 1 and 12 months, and yearly thereafter up to 10 years post-procedure | VARC-3 definitions |
| Non-disabling stroke | at 1 and 12 months, and yearly thereafter up to 10 years post-procedure | VARC-3 definitions |
| Transient Ischemic attack | at 1 and 12 months, and yearly thereafter up to 10 years post-procedure | VARC-3 definitions |
| Cardiovascular mortality | at 1 and 12 months, and yearly thereafter up to 10 years post-procedure | VARC-3 definitions |
| Endocarditis | at 1 and 12 months, and yearly thereafter up to 10 years post-procedure | VARC-3 definitions |
| Valve Thrombosis | at 1 and 12 months, and yearly thereafter up to 10 years post-procedure | VARC-3 definitions |
| Need for aortic valve re-intervention | at 1 and 12 months, and yearly thereafter up to 10 years post-procedure | VARC-3 definitions |
| Bleeding (life-threatening or major) | at 1 and 12 months, and yearly thereafter up to 10 years post-procedure | VARC-3 definitions |
| Vascular complication (major) | at 1 and 12 months, and yearly thereafter up to 10 years post-procedure | VARC-3 defintions |
| Acute kidney injury (stage 2 or 3) | at 1 and 12 months, and yearly thereafter up to 10 years post-procedure | VARC-3 defintions |
| Echocardiographic aortic bioprosthesis performance (degree of paravalvular leakage, valve area, mean gradient, prosthesis patient mismatch) | at discharge, 1 and 12 months, and yearly thereafter up to 10 years post-procedure | VARC-3 definitions |
| NYHA functional class | at 1 and 12 months, and yearly thereafter up to 10 years post-procedure | NYHA functional class |
| Need for permanent pacemaker | at 1 and 12 months, and yearly thereafter up to 10 years post-procedure | VARC-3 definitions |
| New onset atrial fibrillation captured on ECG | at 1 and 12 months, and yearly thereafter up to 10 years post-procedure | VARC-3 definitions |
| Left ventricle remodeling as assesed by echocardiography | at 1 and 12 months, and yearly thereafter up to 10 years post-procedure | Left ventricle internal diameter in diastoli |
| Quality of life change from baseline | at 1 and 12 months, and yearly thereafter up to 10 years post-procedure | Kansas City Cardiomyopathy Questionnaire, scale 0 (worse) to 100 (better) |
| Myocardial Infarction | at 1 and 12 months, and yearly thereafter up to 10 years post-procedure | VARC-3 definitions |
Countries
Denmark, Finland, Iceland, Norway, Sweden
Outcome results
None listed