TAVR vs SAVR in Severe Bicuspid Aortic Stenosis (BELIEVERS)

Bicuspid Aortic Valve Replacement: EvaLuatIon of transcathetEr VERsus Surgery (BELIEVERS) Trial

The study is a multicenter, randomized superiority trial of standard of care therapies for severe aortic stenosis (AS) in patients with a bicuspid aortic valve (BAV).

The two primary comparators in this study are: Transcatheter Aortic Valve Replacement (TAVR), and Surgical Aortic Valve Replacement (SAVR).

TAVR is a minimally invasive transcatheter procedure to treat aortic valve disease..

SAVR is involving the open chest surgery to replace the aortic valve.

The devices and international procedures in this Trial (TAVR or SAVR) are commercially approved by the FDA.

Consented patients who are qualifying for the Trial will be randomized 1:1, meaning they will have an equal chance to be treated with either TAVR or SAVR procedure.

Consented patients who will not qualify for the randomized part of the study will be followed up clinically in either TAVR or SAVR Registry arms.

The study objective is to provide evidence to guide patients and their providers on the most appropriate therapy for valve replacement on this particular BAV anatomy.

Study Overview

• Status: Not yet recruiting
• Conditions: Bicuspid Aortic Valve Disease
• Intervention / Treatment: Procedure: Transcatheter Aortic Valve Replacement; Procedure: the open chest surgery to replace the aortic valve

Detailed Description

Bicuspid aortic valve is a congenital heart condition characterized by the presence of two, rather than the typical three, cusps in the aortic valve.

The condition can lead to various complications, including aortic stenosis (AS; narrowing of the valve opening), aortic regurgitation (leaking of the valve), and an increased risk of aortic aneurysm.

The BELIEVERS trial builds on this foundation, integrating imaging-guided methodologies to create a robust framework for randomization with contemporary technologies and thus provide definitive evidence for treatment of this complex population.

Since the congenital severe bicuspid aortic valve stenosis was considered in most of the cases an exclusion from all large TAVR vs SAVR trials, there is no clear evidence on which procedure would be more efficient for such anatomical condition.

The suitable consented subjects will be randomized 1:1 on either TAVR or SAVR arm. These patients will be followed through clinic visits at 30 days, one year and annually up to 10 years.

• Study Type: Interventional
• Enrollment (Estimated): 1200
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
      • Contact: Mitch Gheorghiu, MD; Phone Number: 310-423-6152; Email: mitch.gheorghiu@cshs.org
      • Contact: Khaled Alsabaawi, MD; Phone Number: 310-423-6226; Email: khaled.alsaabawi@cshs.org

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. 50 years of age or older at time of consent
2. Severe AS deemed suitable for a bioprosthesis by a local heart team (unsuitable or patient declined a mechanical valve or Ross procedure, following demonstration of evidence-based shared decision making with a validated decision-aid(1)
3. Gated contrast CT available and suitable for core laboratory analysis;
4. BAV anatomy confirmed by CT core laboratory analysis

Exclusion Criteria:

1. Recent cardiovascular intervention within 30 days prior to randomization.
2. Presence of an existing TAVR or SAVR device
3. Pregnancy or lactation
4. Extreme or prohibitive TAVR or SAVR risk, adjudicated by Patient Selection Committee (PSC) Review
5. Active enrollment in another investigational study
6. Disproportionate TAVR vs SAVR risk, as adjudicated by the patient selection committee
7. Associated aortopathy (AA≥45mm by maximal cross-sectional dimension, as confirmed by CT core laboratory analysis, or AA<45mm but site plan for surgery of the aorta in the event of randomization to surgery
8. 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)
9. 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)
10. Plan to use any device other than commercially approved Edwards balloon expandable or Medtronic self-expanding TAVR
11. Leukopenia (WBC < 3000 cells/µL), anemia (Hgb < 8 g/dL), Thrombocytopenia (Plt < 50,000 cells/µL) on latest available labs within 30 days prior to randomization
12. Hemodynamic or respiratory instability requiring inotropic support, mechanical ventilation, or mechanical heart assistance within 30 days prior to randomization
13. LVEF < 25% within 90 days prior to randomization
14. Stroke or transient ischemic attack (TIA) within 90 days prior to randomization
15. Renal insufficiency (eGFR < 30 ml/min per the Cockcroft-Gault formula)
16. Severe lung disease (FEV1 < 50% predicted), unresolved prior to randomization
17. History of liver disease defined as MELD Score ≥ 10 or Child-Pugh Class B or C
18. Unable to complete the KCCQ due cognitive impairment or other medical condition

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
Other: Transcatheter Aortic Valve Replacement TAVR; percutaneous approach as modality of treatment	Procedure: Transcatheter Aortic Valve Replacement; This is a transcatheter, percutaneous approach using the commercially approved bioprosthetic valve device to replace the diseased aortic valve
Active Comparator: Surgical Aortic Valve Replacement SAVR; open chest approach as modality of treatment	Procedure: the open chest surgery to replace the aortic valve; This is the open chest surgical approach using the commercially approved bioprosthetic valve device to replace the diseased aortic valve

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To compare the safety and effectiveness of TAVR vs SAVR for the treatment of severe AS in patients with BAV	A hierarchical composite (assessed by Win ratio at latest available follow-up) of: death,; disabling stroke,; non-disabling stroke,; valve reintervention,; rehospitalization†,; unfavorable KCCQ (VARC-3*)	2 years post end of enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-averaged KCCQ	time-weighted mean of KCCQ overall summary score across at follow-up timepoints	3 years post end of enrollment
KCCQ status (serial)	overall summary score at discharge and specified follow-up visits	at 2 years post end of enrollment
SF-12 questionnaire	physical and mental component summary scores at prespecified visits.	at 2 years post end of enrollment
NYHA class	NYHA I-IV at prespecified visits	at 2 years post end of enrollment
6-minute walk test	distance (meters) at prespecified visits.	at 2 years post end of enrollment
PHQ-9 questionnaire	depression score (0-27) at prespecified visits	at 2 years post end of enrollment
Time-to-recovery to baseline (QOR-15)	time from index procedure to first follow-up at which QOR-15 returns to (or exceeds) the participant's pre-procedure baseline (operational rules and handling of missingness specified in SAP).	at 2 years post end of enrolment
Additional clinical time-to event endpoints	death (time-to-first event) and cardiovascular death (time-to-fist event),•All stroke, disabling stroke (time-to-first event). • Rehospitalization (time-to-first event), • Composite of death/stroke/rehospitalization: time to first occurrence of any of death, any stroke, or qualifying rehospitalization. • Aortic dissection: imaging-, operative-, or autopsy-confirmed aortic dissection after randomization. • Need for surgery of the aorta: • CV rehospitalization days	at 2 years post end of enrollment
Secondary Imaging Endpoints	Echocardiography Core Lab• Bioprosthetic valve failure (BVF): • Paravalvular leak (PVL) severity:	at 2 years post end of enrollment
Secondary Imaging Endpoints CT	Ascending aorta dimension >50 mm: maximum ascending aorta diameter measured by CT Core Lab; endpoint met if >50 mm at any follow-up CT• Change in ascending aorta dimension (cm/year): annualized change in maximum ascending aorta diameter from baseline to follow-up CT by CT Core Lab.	at 2 years post end of enrollment

Collaborators and Investigators

• Sponsor: Cedars-Sinai Medical Center
• Collaborators: Patient-Centered Outcomes Research Institute; Icahn School of Medicine at Mount Sinai; Institut universitaire de cardiologie et de pneumologie de Québec, University Laval
• Investigators: Principal Investigator: Raj Makkar, MD, Cedars-Sinai Medical Center; Principal Investigator: Marcio Diniz, PhD, ICAHN School of Medicine at Mount Sinai; Principal Investigator: Vinod Thourani, MD, Emory University

Study record dates

Study Major Dates

• Study Start (Estimated): June 24, 2026
• Primary Completion (Estimated): July 1, 2032
• Study Completion (Estimated): May 10, 2040

Study Registration Dates

• First Submitted: January 30, 2026
• First Submitted That Met QC Criteria: February 9, 2026
• First Posted (Actual): February 17, 2026

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Severe Bicuspid Aortic Valve intervention: TAVR vs SAVR
• Additional Relevant MeSH Terms: Aortic Valve Disease; Cardiovascular Diseases; Heart Diseases; Heart Valve Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Defects, Congenital; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Bicuspid Aortic Valve Disease; Surgical Procedures, Operative; Cardiovascular Surgical Procedures; Cardiac Surgical Procedures; Thoracic Surgical Procedures; Prosthesis Implantation; Heart Valve Prosthesis Implantation; Transcatheter Aortic Valve Replacement
• Other Study ID Numbers: BAV2025-4770

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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