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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Aortic Valve Stenosis
• Intervention / Treatment: Device: TAVR

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 Type: Interventional
• Enrollment (Actual): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Bayern
    • München, Bayern, Germany, 81377
      • Klinikum der Universität München-Großhadern

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: IHF GmbH - Institut für Herzinfarktforschung
• Collaborators: Yale University; Boston Scientific Group
• Investigators: Principal Investigator: Julinda Mehilli, Prof. Dr., University Clinic Munich

Study record dates

Study Major Dates

• Study Start (Actual): July 3, 2019
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: February 27, 2019
• First Submitted That Met QC Criteria: March 4, 2019
• First Posted (Actual): March 5, 2019

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Aortic stenosis; Transcatheter aortic valve replacement; Low flow; Low gradient
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Constriction, Pathologic
• Other Study ID Numbers: REBOOT-PARADOX

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No