Bicuspid Aortic Valve Replacement: Evaluation of Transcatheter Versus Surgery-Pilot Trial (BELIEVE-IT)

Bicuspid Aortic Valve Replacement: EvaLuatIon of transcathetEr Versus surgEry-PILOT Trial

The study protocol is a randomized trial of standard of care therapies for severe aortic stenosis (AS) in patients with a bicuspid aortic valve (BAV). Namely, the therapies to which patients will be randomized will be transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR), in patients deemed clinically suitable for both following heart team review.

The purpose of this study is to compare the safety and efficacy of Transcatheter Aortic Valve Replacement (TAVR) versus Surgical Aortic Valve Replacement (SAVR) for treating patients with severe aortic stenosis (AS) who have a congenital bicuspid aortic valve (BAV) anatomy. Patients with BAV anatomy have been under-represented in previous trials and this study might provide important information to help guide future treatment options.

The study patients will be followed with standard of care procedures for 10 years.

Study Overview

• Status: Recruiting
• Conditions: Aortic Valve Stenosis; Bicuspid Aortic Valve
• Intervention / Treatment: Procedure: transcatheter aortic valve replacement (TAVR); Procedure: surgical aortic valve replacement (SAVR)

• Study Type: Interventional
• Enrollment (Estimated): 250
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mitch Gheorghiu; Phone Number: 310 423-6152; Email: mitch.gheorghiu@cshs.org
• Study Contact Backup: Name: Khaled Alsabaawi; Phone Number: 310 423-6226; Email: khaled.alsabaawi@cshs.org

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Recruiting
      • Cedars-Sinai Medical Center
      • Sub-Investigator: Dominic Emerson, MD
      • Contact: Mitch Gheorghiu; Phone Number: 310-423-6152; Email: Mitch.Gheorghiu@cshs.org
      • Sub-Investigator: Alfredo Trento, MD
      • Contact: Khaled Alsabaawi; Phone Number: 310 423-6226; Email: khaled.alsabaawi@cshs.org
      • Sub-Investigator: Hasan Al-Jilaihawi, MD
      • Sub-Investigator: Joanna Chikwe, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged > 50 years of age
• Site-determined severe AS deemed necessary for treatment with SAVR or TAVR
• Gated contrast CT available and suitable for core laboratory analysis
• BAV anatomy confirmed by CT core laboratory analysis

Exclusion Criteria:

• Recent cardiovascular intervention within the prior 30 days.
• Presence of an existing TAVR or SAVR device
• Pregnancy or lactation
• Extreme or prohibitive TAVR or SAVR risk, determined by site or committee Active enrollment in another investigational study
• Disproportionate TAVR vs SAVR risk, as determined by treating site or committee
• Associated aortopathy (AA≥ 45 mm by maximal cross-sectional dimension, as confirmed by CT core laboratory analysis, or AA<45 mm but site plan for surgery of the aorta in the event of randomization to surgery
• Site plan for treatment of concomitant non-coronary cardiovascular disease in the event of randomization to surgery (for instance, concomitant valve surgery, septal defect or coarctation repair, aorta or root replacement or repair)
• In the presence of coronary artery disease deemed necessary for revascularization in the event of randomization to SAVR or TAVR, Syntax score ≥ 32 or deemed unsuitable for PCI, or deemed unsuitable for coronary artery bypass grafting (CABG).

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: transcatheter aortic valve replacement (TAVR); 50% of patients will be treated with standard TAVR procedure and followed up for 10 years	Procedure: transcatheter aortic valve replacement (TAVR); percutaneous transcatheter aortic valve replacement
Active Comparator: surgical aortic valve replacement (SAVR); 50% of patients will be treated with standard SAVR procedure and followed up for 10 years	Procedure: surgical aortic valve replacement (SAVR); surgical aortic valve replacement

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1 year hierarchical composite outcome of death, disabling stroke, non-disabling stroke, valve reintervention, rehospitalization, unfavorable KCCQ (VARC 3)	The primary endpoint will be analyzed by the Win ratio method14. That is, every patient in the TAVR group will be compared with every patient in the SAVR group to determine which pair has won. A win higher up in the hierarchy takes priority, so KCCQ gets used only for those pairs that were tied on the first 5 event components. Then KCCQ win is declared if the time-averaged change in KCCQ differs by 5 points or more. The win ratio= total wins on TAVR divided by total wins on SAVR, for which a 95% CI and p value is calculated.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Technical success at time of exit from OR/cath lab	defined as meeting of the following: Alive; Successful access, delivery and retrieval of the device delivery system; Deployment and correct positioning (including repositioning/recapture if needed) of the single intended valve; No additional unplanned or emergency surgery or re-intervention prior to leaving OR/Cath lab related to the device or access procedure (includes need for return to bypass post initial wean	exit from procedure (OR or cath lab)
Device success	Defined as meeting all of the following: Alive and stroke-free; Original intended device in place; No additional surgical or interventional procedures related to access or the device since completion of the original procedure (i.e., exit from the cath lab/OR); Intended performance of the device:Structural performance: No migration, embolization, detachment, fracture, or thrombosisHemodynamic performance: Mean gradient < 20mmHg, AVA >1cm2, jet velocity < 3.0 m/sAbsence of the following para-device complications (PVL > mild, erosion, hemolysis, or endocarditis)	30 days
Procedural success	Defined as meeting all of the following: Life-threatening bleed (BARC 3b or greater); Major vascular or cardiac structural complications requiring unplanned reintervention or surgery; Stage 2 or 3 AKI (includes new dialysis); MI or need for PCI/CABG; Severe heart failure or hypotension requiring IV inotrope >12 hours, ultrafiltration or mechanical circulatory support; Prolonged intubation > 48 hours; Need for a permanent pacemaker implant or continuous, new onset atrial fibrillation	30 Days
Patient success	Defined as meeting all of the following: Device success; No re-hospitalizations or re-interventions for the underlying condition (e.g., Aortic stenosis and Heart Failure); Return to prior living arrangement (or equivalent); Improvement in symptoms defined as increase in NYHA Class > 1 compared to Baseline; Improvement in functional status defined as 6MWT > 25 m compared to Baseline; Improvement in quality-of-life defined as KCCQ score > 10 compared to Baseline	1 year

Collaborators and Investigators

• Sponsor: Cedars-Sinai Medical Center
• Investigators: Principal Investigator: Raj Makkar, MD, Cedars-Sinai Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2025
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2037

Study Registration Dates

• First Submitted: February 5, 2025
• First Submitted That Met QC Criteria: February 5, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 5, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: TAVR; BAV; SAVR
• Additional Relevant MeSH Terms: Aortic Valve Disease; Cardiovascular Diseases; Heart Diseases; Ventricular Outflow Obstruction; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Defects, Congenital; Bicuspid Aortic Valve Disease; Aortic Valve Stenosis; Heart Valve Diseases
• Other Study ID Numbers: STUDY00003805

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