Clinical trial NCT06830499: Sapien 3 Transcatheter Aortic Valve Replacement in Young Aortic Valve Stenosis Patients from China
Official title: Safety, Effectiveness and Durability of Sapien 3 Transcatheter Aortic Valve Replacement in Young Aortic Valve Stenosis Patients from China
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: AORTIC VALVE DISEASES
Bicuspid Aortic Valve (BAV)
Keywords: TAVR
real-world
aortic valve stenosis
Sapien 3
Lead sponsor: Xijing Hospital
Sponsor class: OTHER
Collaborators: name: Shanghai Zhongshan Hospital
name: Fu Wai Hospital, Beijing, China
name: West China Hospital
First posted: 2025-02-17
Enrollment: 450
Sex: ALL
Minimum age (years): 50
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Young (50\~70 years old) Chinese patients with severe symptomatic AS, including Type-1 bicuspid population

Brief summary: Safety, effectiveness and durability of Sapien 3 transcatheter aortic valve replacement in young aortic valve stenosis patients from China：A multi-center, retrospective and prospective, single arm, observational study

Detailed description: Transcatheter aortic valve replacement (TAVR) has revolutionized the treatment of patients with severe aortic stenosis (AS). Currently TAVR indication has expanded to intermediate and low-risk patients from inoperable or high-risk patients, through a rigorous series of clinical trials comparing TAVR with surgical aortic valve replacement (SAVR).

Despite 2020 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines recommended SAVR for patients with symptomatic severe AS aged \<65 years, the previous data from United States nationwide Vizient Clinical Data Base and Northern New England Cardiovascular Disease Group Consortium (NNECDSG) registry demonstrated dramatic growth in TAVR utilization in younger patients aged \<65 years from 2015 to 2021/2022, which is possibly driven by increased TAVR utilization in low surgical risk patients.

However, TAVR has never been systematically tested in young (\<65 years old), low-risk patients, with many unanswered questions, especially the safety and effectiveness of TAVR in patients with bicuspid aortic valves and the durability of transcatheter heart valves. Furthermore, we noticed that the patients between 65 years old and 70 years old accounted for 23.3% of all the TAVR patients and this patient subgroup were underrepresented in the previous study, which makes it necessary to also explore the interested endpoints in this subgroup.

The aim of this study is to establish the safety and efficacy of Sapien 3 TAVR in young (50\~70 years old) Chinese patients with severe symptomatic AS, including Type-1 bicuspid population and to explore the durability performance of Sapien 3 in this cohort.

Eligibility criteria: Inclusion Criteria:

Subjects must meet ALL of the following inclusion criteria to be eligible for participation:

* 50 years of age or older but ≤70 years old at time of consent.
* Severe AS, defined as follows:

  a) For symptomatic patients: i) Aortic valve area ≤1.0 cm2 (or aortic valve area index of ≤0.6 cm2/m2), OR mean gradient ≥40 mm Hg, OR Maximal aortic valve velocity ≥4.0 m/sec by transthoracic echocardiography at rest b) For asymptomatic patients: i) Very severe AS with an aortic valve area of ≤1.0 cm2 (or aortic valve area index of ≤0.6 cm2/m2), AND maximal aortic velocity ≥5.0 m/sec, or mean gradient ≥60 mm Hg by transthoracic echocardiography at rest, OR ii) Aortic valve area of ≤1.0 cm2 (or aortic valve area index of ≤0.6 cm2/m2), AND a mean gradient ≥40 mm Hg or maximal aortic valve velocity ≥4.0 m/sec by transthoracic echocardiography at rest, AND an exercise tolerance test that demonstrates a limited exercise capacity, abnormal BP response, or arrhythmia OR iii) Aortic valve area of ≤1.0 cm2 (or aortic valve area index of ≤0.6 cm2/m2), AND mean gradient ≥40 mmHg, or maximal aortic valve velocity ≥4.0 m/sec by transthoracic echocardiography at rest, AND a left ventricular ejection fraction \<50%.
* Tricuspid aortic valve stenosis and type-1 bicuspid aortic valve anatomy confirmed by MDCT.
* The subject and the treating physician agree that the subject will return for all required post-procedure follow-up visits.
* Adequate iliofemoral access and acceptable level of vessel calcification and tortuosity for safe device implant.
* The study patient has been informed of the nature of the study, agrees to its provisions and has provided written informed consent as approved by the Institutional Review Board (IRB) of the respective clinical site.

Exclusion Criteria:

Subjects are NOT eligible for participation if they meet ANY of the following exclusion criteria:

* Any of the following: a. no calcification; b. challenging calcification based on physician's experience and discretion (Case Review Board would decide whether to exclude challenging calcification cases).
* Aortic valve is a congenital unicuspid valve, congenital Type-0 or Type-2 bicuspid valve, or quadricuspid valve.
* Severe femoral, iliac or aortic atherosclerosis, calcification, coarctation, aneurysm or tortuosity, which prevents transfemoral TAVR.
* Evidence of an acute myocardial infarction ≤ 1 month (30 days), with evidence of myocardial necrosis in a clinical setting consistent with acute myocardial ischemia.
* Need for open heart surgery (including severe aortic regurgitation, mitral regurgitation or stenosis, or tricuspid regurgitation, congenital heart disease, AF, complex coronary artery disease).
* Aortic disease: a. bicuspid aortic valve with an ascending aorta diameter ≥ 45mm b. tricuspid aortic valve with an ascending aorta diameter ≥ 50mm.
* Pre-existing mechanical or bioprosthetic valve in any position.
* Hemodynamic or respiratory instability requiring inotropic support, mechanical ventilation or mechanical heart assistance within 30 days of the screening visit.
* Emergency interventional/surgical procedures within 30 days of the valve implant procedure.
* Hypertrophic cardiomyopathy with or without obstruction.
* Ventricular dysfunction with LVEF \< 30%.
* Cardiac imaging (echo, CT, and/or MRI) evidence of ventricular mass, thrombus or vegetation.
* Inability (including allergy) to heparin, iodine contrast agent, warfarin or NOAC, aspirin or clopidogrel.
* Stroke or transient ischemic attack (TIA) within 180 days of the valve implant procedure.
* Renal replacement therapy at the time of screening.
* Severe lung disease (FEV1 \< 50% predicted) or currently on home oxygen.
* Estimated life expectancy \< 24 months.
* 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. Observational studies are not considered exclusionary.

Primary outcomes:
measure: The incidence of all-cause mortality, stroke, rehospitalization
timeFrame: 30 days and 1 year
measure: A composite of device success
timeFrame: 30 days
measure: The durability performance of Sapien 3
timeFrame: 1, 3, 5 years
Secondary outcomes:
measure: Annular rupture
timeFrame: At 1 day of discharge
measure: Paravalvular leakage
timeFrame: At 1 day of discharge, 30 days, 1, 3, 5 years
measure: Technical success
timeFrame: At exit from procedure room
measure: Procedural success
timeFrame: At 30 days
measure: Mortality (all cause & cardiovascular)
timeFrame: At 30 days, 1, 3, 5 years
measure: Stroke (disabling and nondisabling)
timeFrame: At 30 days, 1, 3, 5 years
measure: Rehospitalization (procedure, valve and heart failure related)
timeFrame: At 30 days, 1, 3, 5 years
measure: Major vascular complication
timeFrame: At 30 days, 1, 3, 5 years
measure: Major or life-threatening bleeding
timeFrame: At 30 days, 1, 3, 5 years
measure: Myocardial infarction
timeFrame: At 30 days, 1, 3, 5 years
measure: Acute kidney injury stage 2 or 3
timeFrame: At 30 days, 1, 3, 5 years
measure: Need for a permanent pacemaker
timeFrame: At 30 days, 1, 3, 5 years
measure: New onset atrial fibrillation
timeFrame: At 30 days, 1, 3, 5 years
measure: Valve endocarditis
timeFrame: At 30 days, 1, 3, 5 years
measure: Valve thrombosis
timeFrame: At 30 days, 1, 3, 5 years
measure: New York Heart Association class
timeFrame: At 30 days, 1, 3, 5 years
measure: Patient-prosthesis mismatch
timeFrame: At 30 days, 1, 3, 5 years
measure: Health status as evaluated by Quality of Life questionnaires - KCCQ
timeFrame: At baseline, 30 days, 1, 3, 5 years
Other outcomes:
Locations:
city: Xi'an
country: China
facility: Department of Cardiovascular Surgery of Xijing Hospital, Air Force Military Medical University
state: Shaanxi
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Beijing
country: China
facility: Fuwai Hospital, Chinese Academy of Medical Sciences
city: Shanghai
country: China
facility: Shanghai Zhongshan Hospital, Fudan University
Study officials:
affiliation: Department of Cardiovascular Surgery of Xijing Hospital, Air Force Military Medical University
name: Jian Yang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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