Bicuspid Aortic Valve Disease
Conditions
Keywords
Severe Bicuspid Aortic Valve intervention: TAVR vs SAVR
Brief summary
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
PROCEDURETranscatheter Aortic Valve Replacement
This is a transcatheter, percutaneous approach using the commercially approved bioprosthetic valve device to replace the diseased aortic valve
PROCEDUREthe 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
Sponsors
Cedars-Sinai Medical Center
Patient-Centered Outcomes Research Institute
Icahn School of Medicine at Mount Sinai
Institut universitaire de cardiologie et de pneumologie de Québec, University Laval
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The comparator groups are TAVR and SAVR in patients over the age of 50 presenting for a bioprosthesis for severe aortic stenosis and bicuspid aortic valve anatomy. TAVR has shown superiority over SAVR in tricuspid aortic valve (TAV) anatomy in a randomized clinical trial53. However, although TAVR and SAVR have been widely used for BAV, there is to date no randomized trial or even systematic propensity matched data comparing TAVR and SAVR in BAV. The treatments of TAVR and SAVR are standard of care treatments, but the selection of one or the other in bicuspid anatomy remains arbitrary, with no clear framework available for patients and their physicians.
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To compare the safety and effectiveness of TAVR vs SAVR for the treatment of severe AS in patients with BAV | 2 years post end of enrollment | A hierarchical composite (assessed by Win ratio at latest available follow-up) of: 1. death, 2. disabling stroke, 3. non-disabling stroke, 4. valve reintervention, 5. rehospitalization†, 6. unfavorable KCCQ (VARC-3\*) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time-averaged KCCQ | 3 years post end of enrollment | time-weighted mean of KCCQ overall summary score across at follow-up timepoints |
| KCCQ status (serial) | at 2 years post end of enrollment | overall summary score at discharge and specified follow-up visits |
| SF-12 questionnaire | at 2 years post end of enrollment | physical and mental component summary scores at prespecified visits. |
| NYHA class | at 2 years post end of enrollment | NYHA I-IV at prespecified visits |
| 6-minute walk test | at 2 years post end of enrollment | distance (meters) at prespecified visits. |
| PHQ-9 questionnaire | at 2 years post end of enrollment | depression score (0-27) at prespecified visits |
| Time-to-recovery to baseline (QOR-15) | at 2 years post end of enrolment | 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). |
| Additional clinical time-to event endpoints | at 2 years post end of enrollment | 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 |
| Secondary Imaging Endpoints | at 2 years post end of enrollment | Echocardiography Core Lab• Bioprosthetic valve failure (BVF): • Paravalvular leak (PVL) severity: |
| Secondary Imaging Endpoints CT | at 2 years post end of enrollment | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORRaj Makkar, MD
Cedars-Sinai Medical Center
PRINCIPAL_INVESTIGATORMarcio Diniz, PhD
Icahn School of Medicine at Mount Sinai
PRINCIPAL_INVESTIGATORVinod Thourani, MD
Emory University
Outcome results
None listed