accuRate Evaluation of Benefit With Optimal Medical Treatment With or Without Transcatheter Valve Repair of PARADOXical Low Flow Low Gradient Aortic Stenosis

Study Overview
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Brief Summary
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Aim of this study is to evaluate whether microsurgical repair or replacement of the aortic valve is a treatment option for a subgroup of patients suffering from aortic Stenosis.

Detailed Description
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Stenosis of the aortic valve leads to a narrowing of the valve, consequently to low blood flow from the heart into the Aorta, and is associated with symptoms like fatigue, breathlessness, dizziness, fainting, and chest pain. For many of the patients suffering from severe aortic stenosis surgical or catheter-assisted repair or replacement of the damaged aortic valve has been proven to be a safe and effective treatment option. Probably about 20-30% of patients suffering from severe aortic stenosis display a deviation from the usually observed disease pattern: These patients do not show the typical high pressure difference between the left ventricle (heart chamber) and the aorta (transvalvular gradient; paradoxical low flow/low gradient aortic stenosis). For these patients it is not yet clear, if microsurgical repair of the aortic valve (transcatheter aortic valve repair - TAVR) should be a treatment option as well. REBOOT-PARADOX evaluates whether TAVR is advantageous compared to optimal medical Treatment alone for patients suffering from paradoxical aortic stenosis. Two thirds of the participating patients will be treated by TAVR, one third will receive medical Treatment alone.

Official Title
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Optimal Medical Treatment With or Without Valve Repair in Patients With Symptomatic Paradoxical Low-Flow, Low-Gradient Aortic Stenosis - a Multi-center, Randomized Comparison

Conditions
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Aortic Valve Stenosis

Intervention / Treatment
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* Device: TAVR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: I1. Patients with symptomatic native aortic valve stenosis and age ≥18 years I2. Aortic valve area (AVA) ≤ 1 cm2 or indexed AVA ≤ 0.6 cm2/m2, mean aortic gradient < 40 mmHg and stroke volume index (SVI) < 35ml/m2 I3. Left ventricular ejection fraction ≥ 50% I4. MDCT aortic valve calcium score men > 2000AU, women > 1200AU OR the likelihood criteria are fulfilled (symptoms without other explanation and LV hypertrophy; age < 70 yrs., AVS < 0.8 cm2; SVI < 35ml/m2 confirmed by 3D TOE, MRI or invasive; reduced LV longitudinal function without other reason) I5. Heart team agrees on eligibility for TAVR I6. Written informed consent I7. Negative pregnancy test in women with childbearing potential Exclusion Criteria: E1. Hemodynamic instability E2. Cardiogenic shock E3. Pre-existing mechanical or bio-prosthetic valve in any position E4. Concomitant severe valvular heart disease E5. Pre-existing or active endocarditis E6. Need for heart surgery due to other conditions E7. Aortic valve is congenital unicuspid or congenital bicuspid E8. Hypertrophic cardiomyopathy with or without obstruction E9. Echocardiographic evidence of intracardiac mass, thrombus or vegetation E10. Acute myocardial infarction within 1 month before intended AS-treatment E11. Renal replacement therapy E12. Estimated life expectancy < 24 months (730 days) due to carcinomas end stage liver disease or renal disease E13. Currently participating in an investigational drug or another device study. Note: Trials requiring extended follow-up for products that were investigational, but have since become commercially available, are not considered investigational trials. E14. Patient refuses aortic valve repair

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective, controlled, randomized (2:1), parallel group, open-label, multi-centre, international
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: TAVR Group<br>Patients will be treated by transcatheter aortic valve repair (TAVR). | Device: TAVR<br>* Repair of defective aortic valve by microsurgical Intervention.<br>|
| No Intervention: Medical Treatment Group<br>Patients will receive optimal medical treatment alone. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to death | All-cause mortality | 24 months after last-patient-in | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiovascular mortality | Death because of cardiovascular events | 5 years after index treatment | 
| Re-hospitalization due to heart failure | Number of hospital stays after randomization | 5 years after index treatment | 
| Incidence of neurological events - incidence of strokes | Number of strokes | 5 years after randomization | 
| Incidence of neurological Events - incidence of transient ischaemic attacks | Number of transient ischaemic attacks | 5 years after randomization | 
| Cardiac functionality - left ventricular function | Echocardiographic measurement of left ventricular ejection fraction in % | 5 years after randomization | 
| Cardiac functionality - aortic valve hemodynamics | Measurement of aortic pressure in mmHg | 5 years after randomization | 
| Patients' quality of life | EQ5D-score in % | 5 years after randomization | 
| Device reliability | Number of reinterventions (TAVR arm only) | 5 years after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aortic stenosis, Low flow, Low gradient, Transcatheter aortic valve replacement