Clinical trial NCT03863132: accuRate Evaluation of Benefit With Optimal Medical Treatment With or Without Transcatheter Valve Repair of PARADOXical Low Flow Low Gradient Aortic Stenosis
Official title: Optimal Medical Treatment With or Without Valve Repair in Patients With Symptomatic Paradoxical Low-Flow, Low-Gradient Aortic Stenosis - a Multi-center, Randomized Comparison
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Aortic Valve Stenosis
Keywords: Aortic stenosis
Low flow
Low gradient
Transcatheter aortic valve replacement
Lead sponsor: IHF GmbH - Institut für Herzinfarktforschung
Sponsor class: OTHER
Collaborators: name: Boston Scientific Group
name: Yale University
First posted: 2019-03-05
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, controlled, randomized (2:1), parallel group, open-label, multi-centre, international
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Time to death
timeFrame: 24 months after last-patient-in
Secondary outcomes:
measure: Cardiovascular mortality
timeFrame: 5 years after index treatment
measure: Re-hospitalization due to heart failure
timeFrame: 5 years after index treatment
measure: Incidence of neurological events - incidence of strokes
timeFrame: 5 years after randomization
measure: Incidence of neurological Events - incidence of transient ischaemic attacks
timeFrame: 5 years after randomization
measure: Cardiac functionality - left ventricular function
timeFrame: 5 years after randomization
measure: Cardiac functionality - aortic valve hemodynamics
timeFrame: 5 years after randomization
measure: Patients' quality of life
timeFrame: 5 years after randomization
measure: Device reliability
timeFrame: 5 years after randomization
Other outcomes:
Locations:
city: München
country: Germany
facility: Klinikum der Universität München-Großhadern
state: Bayern
Study officials:
affiliation: University Clinic Munich
name: Julinda Mehilli, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: