Clinical trial NCT05511792: Down Sizing Strategy (HANGZHOU Solution) vs Standard Sizing Strategy TAVR in Bicuspid Aortic Stenosis (Type 0)
Official title: Transcatheter Aortic Valve Replacement For Patients With Bicuspid Aortic Stenosis (Type 0) Using Down Sizing Strategy Compared With Standard Sizing Strategy (HANGZHOU Solution): A Prospective, Multicenter, Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Aortic Stenosis With Bicuspid Valve
Lead sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sponsor class: OTHER
First posted: 2022-08-23
Enrollment: 206
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To compare down sizing strategy versus annular sizing strategy technique (control group) in Type 0 bicuspid aortic stenosis (AS) patients undergoing transcatheter aortic valve replacement (TAVR) with self-expanding valves (SEVs): a randomized superiority trial

Detailed description: Transcatheter aortic valve replacement (TAVR) has emerged as a favorable alternative for severe symptomatic aortic stenosis (AS) patients of all surgical risk profiles. Patients with bicuspid aortic valve (BAV) underwent TAVR had similar 30-day mortality as well as stroke and new pacemaker implantation rates compared to tricuspid aortic valve (TAV) subjects, but carried higher risk of moderate/severe perivalvular leakage (PVL), conversion to surgery and device failure. Clinical experience in China suggests BAV and heavy calcium burden are more common among TAVR candidates than US/EU cohorts.

Morphological characteristics at supra-annular structure (from annulus to the level of sinotubular junction) are quite complex in BAV, especially concomitant with heavily calcified leaflets. From our previous single center clinical practice, "waist sign" above the annulus during balloon aortic valvuloplasty in TAVR was often observed in patients with bicuspid AS, suggesting that supra-annular structures are the most constrained portion of BAV anatomy where the prosthesis anchors and seals. Therefore, we developed a balloon based supra-annular sizing strategy for self-expanding valves implantation in BAV and the device failure rate as well as pacemaker implantation rates were relatively low as shown in previous cohort study. Several other studies have also achieved successful outcomes associated with device "down sizing" (using a device smaller than that recommended by annular sizing).

The aim of this study is to compare "down sizing"strategy (experimental group) versus annular sizing strategy (control group) in BAV patients undergoing TAVR with self-expanding valves.

Eligibility criteria: Inclusion criteria:

1. Age ≥ 65 years;
2. Age \<65 years and age ≥ 60 years with high surgical risk after combing STS Risk Estimate (≥ 8%), Katz activities of Daily Living, major Organ System Dysfunction and Procedure-Specific Impediment;
3. Severe, bicuspid aortic stenosis: Mean gradient ≥40 mmHg OR Maximal aortic valve velocity ≥4.0 m/sec OR Aortic valve area ≤1.0 cm2 (or aortic valve area index of ≤0.6 cm2/m2); if SVi \<35mL/m2, low-dose dobutamine stress echocardiography is required;
4. NYHA classification ≥ II;
5. Type 0 (Sievers classification) by MDCT;
6. Perimeter-derived annulus diameter ranges from 20.0 mm to 26.0 mm;
7. Candidate for Transfemoral TAVR;
8. 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)/Ethics Committee (EC) of the respective clinical site.

Exclusion Criteria:

1. Any contra-indication for Self-expanding bioprosthetic aortic valve deployment Leukopenia (WBC \< 3000 cell/mL), acute anemia (Hgb \< 9 g/dL), Thrombocytopenia (Plt\< 50,000 cell/mL).
2. Active sepsis, including active bacterial endocarditis with or without treatment;
3. Evidence of an acute myocardial infarction ≤ 1 month (30 days) before the intended treatment \[(defined as: Q wave MI, or non-Q wave MI with total CK elevation of CK-MB ≥ twice normal in the presence of MB elevation and/or troponin level elevation (WHO definition)\].
4. Stroke or transient ischemic attack (TIA) within 3 months (90 days) of the procedure.
5. Estimated life expectancy \< 12 months (365 days) due to carcinomas, chronic liver disease, chronic renal disease or chronic end stage pulmonary disease.
6. Any Emergent surgery required before TAVR procedure.
7. A known hypersensitivity or contraindication to any of the following that cannot be adequately medicated:aspirin or heparin (HIT/HITTS) and bivalirudin; clopidogrel; Nitinol (titanium or nickel); contrast media
8. Gastrointestinal (GI) bleeding that would preclude anticoagulation.
9. Subject refuses a blood transfusion.
10. Severe dementia (resulting in either inability to provide informed consent for the study/procedure, prevents independent lifestyle outside of a chronic care facility, or will fundamentally complicate rehabilitation from the procedure or compliance with follow-up visits).
11. Other medical, social, or psychological conditions that in the opinion of the investigator precludes the subject from appropriate consent or adherence to the protocol required follow-up exams.
12. Currently participating in an investigational drug or another device study (excluding registries).
13. Hypertrophic cardiomyopathy (HCM with myocardium more than 1.5cm without an identifiable cause) with obstruction (HOCM).
14. Echocardiographic evidence of intracardiac mass, thrombus or vegetation.
15. Severe mitral stenosis amenable to surgical replacement or repair.
16. Aortic valve type cannot be determined (Sievers classification).
17. Significant aortic disease, including marked tortuosity (hyperacute bend), aortic arch atheroma \[especially if thick (\> 5 mm), protruding or ulcerated\] or narrowing (especially with calcification and surface irregularities) of the abdominal or thoracic aorta, severe"unfolding" and horizontal aorta(Annular Angulation\>70°).
18. Ascending aorta diameter \> 50 mm.
19. Aortic or iliofemoral vessel characteristics that would preclude safe placement of the introducer sheath.
20. Patient is considered high risk for TAVR by CT corelab, including coronary obstruction, annular rupture and other severe TAVR-Related complications.
21. Previous pacemaker implantation.

Primary outcomes:
measure: Composite endpoint of Clinical Event Rate of Device Success (VARC-3), Free of pacemaker implantation, and Free of new onset complete left bundle branch block at 1 month
timeFrame: 1 month after index procedure
Secondary outcomes:
measure: New onset complete left bundle branch block
timeFrame: 1 month after index procedure
measure: Permanent pacemaker implantation
timeFrame: 1 month after index procedure
measure: Device success Rate
timeFrame: 1 month after index procedure
measure: More than (≥) moderate regurgitation
timeFrame: 1 month after index procedure
Other outcomes:
Locations:
city: Xiamen
country: China
facility: Xiamen Cardiovascular Hospital Xiamen University
state: Fujian
city: Lanzhou
country: China
facility: Lanzhou University First Hospital
state: Gansu
city: Guangzhou
country: China
facility: Nanfang Hospital of Southern Medical University
state: Guangdong
city: Guangzhou
country: China
facility: SUN YAT-SEN MEMORIAL HOSPITAL SUN YAT-SEN University
state: Guangdong
city: Yulin
country: China
facility: Yulin First People's Hospital
state: Guangxi
city: Zhengzhou
country: China
facility: Zhengzhou Seventh People's Hospital
state: Henan
city: Changsha
country: China
facility: The Second XIANGYA Hospital Of Central South University
state: Hunan
city: Xi'an
country: China
facility: First Affiliated Hospital of Xi 'an Jiaotong University
state: Shaanxi
city: Qingdao
country: China
facility: Affiliated Hospital of Qingdao University
state: Shandong
city: Qingdao
country: China
facility: Qingdao Municipal Hospital
state: Shandong
city: Urumqi
country: China
facility: Xinjiang Uygur Autonomous Region People's Hospital
state: Xinjiang
city: Hangzhou
country: China
facility: The Second Affiliated Hospital Zhejiang University School of Medicine.
state: Zhejiang
city: Ningbo
country: China
facility: Ning Bo First Hospital
state: Zhejiang
Study officials:
affiliation: 2nd Affiliated Hospital, School of Medicine, Zhejiang University, China
name: Jian' an Wang, PhD, MD
role: STUDY_CHAIR
References: