TAVR vs SAVR in Severe Bicuspid Aortic Stenosis

Official title

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

Overview

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.

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.

Interventions

• Procedure Transcatheter Aortic Valve Replacement
  This is a transcatheter, percutaneous approach using the commercially approved bioprosthetic valve device to replace the diseased aortic valve
• 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

Primary outcome measures

• To compare the safety and effectiveness of TAVR vs SAVR for the treatment of severe AS in patients with BAV [Time frame: 2 years post end of enrollment]

Secondary outcome measures (10)

• Time-averaged KCCQ [Time frame: 3 years post end of enrollment]
• KCCQ status (serial) [Time frame: at 2 years post end of enrollment]
• SF-12 questionnaire [Time frame: at 2 years post end of enrollment]
• NYHA class [Time frame: at 2 years post end of enrollment]
• 6-minute walk test [Time frame: at 2 years post end of enrollment]
• PHQ-9 questionnaire [Time frame: at 2 years post end of enrollment]
• Time-to-recovery to baseline (QOR-15) [Time frame: at 2 years post end of enrolment]
• Additional clinical time-to event endpoints [Time frame: at 2 years post end of enrollment]
• Secondary Imaging Endpoints [Time frame: at 2 years post end of enrollment]
• Secondary Imaging Endpoints CT [Time frame: at 2 years post end of enrollment]

Eligibility criteria

Inclusion criteria

• 50 years of age or older at time of consent
• 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)
• Gated contrast CT available and suitable for core laboratory analysis;
• BAV anatomy confirmed by CT core laboratory analysis

Exclusion criteria

• Recent cardiovascular intervention within 30 days prior to randomization.
• Presence of an existing TAVR or SAVR device
• Pregnancy or lactation
• Extreme or prohibitive TAVR or SAVR risk, adjudicated by Patient Selection Committee (PSC) Review
• Active enrollment in another investigational study
• Disproportionate TAVR vs SAVR risk, as adjudicated by the patient selection committee
• 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
• 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)
• Plan to use any device other than commercially approved Edwards balloon expandable or Medtronic self-expanding TAVR
• 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
• Hemodynamic or respiratory instability requiring inotropic support, mechanical ventilation, or mechanical heart assistance within 30 days prior to randomization
• LVEF < 25% within 90 days prior to randomization
• Stroke or transient ischemic attack (TIA) within 90 days prior to randomization
• Renal insufficiency (eGFR < 30 ml/min per the Cockcroft-Gault formula)
• Severe lung disease (FEV1 < 50% predicted), unresolved prior to randomization
• History of liver disease defined as MELD Score ≥ 10 or Child-Pugh Class B or C
• Unable to complete the KCCQ due cognitive impairment or other medical condition

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Cedars-Sinai Medical Center — Los Angeles

Identifiers

NCT: NCT07413965 · BAV2025-4770

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗