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

Sponsor

IHF GmbH - Institut für Herzinfarktforschung (Other)

Overall Status

Recruiting

CT.gov ID

NCT03863132

Collaborator

Boston Scientific Group (Other), Yale University (Other)

783

Enrollment

Location

Arms

Anticipated Duration (Months)

8.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Aortic Valve Stenosis	Device: TAVR	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

783 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Prospective, controlled, randomized (2:1), parallel group, open-label, multi-centre, internationalProspective, controlled, randomized (2:1), parallel group, open-label, multi-centre, international

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jul 3, 2019

Anticipated Primary Completion Date :

Jul 1, 2026

Anticipated Study Completion Date :

Dec 1, 2026

Arms and Interventions

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

Arm

Intervention/Treatment

Active Comparator: TAVR Group

Patients will be treated by transcatheter aortic valve repair (TAVR).

Device: TAVR

Repair of defective aortic valve by microsurgical Intervention.

No Intervention: Medical Treatment Group

Patients will receive optimal medical treatment alone.

Outcome Measures

Primary Outcome Measures

Time to death [24 months after last-patient-in]
All-cause mortality

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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