Clinical trial NCT04722796: HANGZHOU Solution in Bicuspid AS Undergoing TAVR
Official title: HANGZHOU Solution for Patients With Bicuspid Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement by Using Supra-annular Structure Based Balloon Sizing Strategy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Aortic Stenosis
Aortic Stenosis With Bicuspid Valve
Keywords: Transcatheter aortic valve replacement
Aortic Stenosis with Bicuspid Valve
supra-annular sizing
Lead sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sponsor class: OTHER
Collaborators: name: Venus MedTech (HangZhou) Inc.
name: The First Affiliated Hospital of Bengbu Medical University
name: Chinese PLA General Hospital
name: Fujian Medical University Union Hospital
name: Xiamen University Affiliated Cardiovascular Hospital
name: The Second People's Hospital of GuangDong Province
name: Chinese Academy of Medical Sciences, Fuwai Hospital
name: The First Affiliated Hospital of Zhengzhou University
name: Henan Provincial Chest Hospital
name: Wuhan Union Hospital, China
name: Central South University
name: Northern Jiangsu People's Hospital
name: The First Affiliated Hospital of Nanchang University
name: Second Affiliated Hospital of Nanchang University
name: The Affiliated Hospital of Qingdao University
name: Shanxi Cardiovascular Hospital
name: Tianjin Chest Hospital
name: Ning Bo First Hospital
First posted: 2021-01-25
Enrollment: 508
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 supra-annular sizing and THV implantation technique (Hangzhou solution) versus annular sizing and THV implantation technique (control group) in 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 from low to high surgical risk. BAV patients treated with TAVR had similar 30-day mortality as well as stroke and new pacemaker implantation rates compared to TAV subjects, but carried higher risk of moderate/severe PVL, conversion to surgery and device failure. Event rates significantly decreased with the use of new-generation devices, but TAVR still showed better procedural results in TAV compared to BAV.

Clinical experience in China suggests bicuspid aortic valves and heavy calcium burden are more common among TAVR candidates. Morphological characteristics at supra-annular structure (from annulus to the level of sinotubular junction) are quite complex in bicuspid AS, especially concomitant with heavily calcified leaflets. Because only two leaflet hinge points provide the definition of the annulus plane, current CT-based annulus measurements might not be accurate under these circumstances. From previous single center clinical practice, "waist sign" above the annulus during balloon aortic valvuloplasty in TAVR was often observed in patients with bicuspid AS, indicating that the supra-annular structure may serve a key role in anchoring the THV.

Therefore, we developed a balloon based supra-annular sizing strategy (Hangzhou Solution) for SEV implantation in bicuspid AS. From our single center experience, the device success rate and pacemaker implantation rate were relatively low.

The aim of this study is to compare supra-annular sizing and THV implantation technique (Hangzhou solution) versus annular sizing and THV implantation technique (control group) in bicuspid aortic stenosis (AS) patients undergoing transcatheter aortic valve replacement (TAVR) with self-expanding valves (SEVs).

Eligibility criteria: Inclusion Criteria:

* Age ≥ 65 years
* Age \<65 years and age ≥ 60 years with high surgical risk after combing STS Risk Estimate, Katz activities of Daily Living, major Organ System Dysfunction and Procedure-Specific Impediment;
* Severe, bicuspid aortic stenosis:
* Mean gradient ≥40 mmHg
* Maximal aortic valve velocity ≥4.0 m/sec
* Aortic valve area ≤1.0 cm2 (or aortic valve area index of ≤0.6 cm2/m2)
* NYHA classification ≥ II;
* Type 0, type 1 (Sievers classification) by MDCT
* Perimeter-derived annulus diameter ranges from 20.0 mm to 29.0 mm;
* Transfemoral TAVR
* 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:

* 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).
* Active sepsis, including active bacterial endocarditis with or without treatment;
* Evidence of an acute myocardial infarction ≤ 1 month (30 days) before the intended treatment \[(defined as: Q wave MI, or non-Q wave MI with total CK elevation of CK-MB ≥ twice normal in the presence of MB elevation and/or troponin level elevation (WHO definition)\].
* Stroke or transient ischemic attack (TIA) within 3 months (90 days) of the procedure.
* Estimated life expectancy \< 12 months (365 days) due to carcinomas, chronic liver disease, chronic renal disease or chronic end stage pulmonary disease.
* Any Emergent surgery required before TAVR procedure.
* 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
* Gastrointestinal (GI) bleeding that would preclude anticoagulation.
* Subject refuses a blood transfusion.
* 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).
* 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.
* Currently participating in an investigational drug or another device study (excluding registries).
* Hypertrophic cardiomyopathy (HCM with myocardium more than 1.5cm without an identifiable cause) with obstruction (HOCM).
* Echocardiographic evidence of intracardiac mass, thrombus or vegetation.
* Severe mitral stenosis amenable to surgical replacement or repair.
* Aortic valve type cannot be determined (Sievers classification).
* 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°).
* Ascending aorta diameter \> 50 mm.
* Aortic or iliofemoral vessel characteristics that would preclude safe placement of the introducer sheath.
* Patient is considered high risk for TAVR by CT corelab, including coronary obstruction, annular rupture and other severe TAVR-Related complications.
* Previous pacemaker implantation.

Primary outcomes:
measure: Composite of all-cause mortality rate, disabling stroke rate, new permanent pacemaker implantation rate and moderate or severe prosthetic valve regurgitation rate at 1 month
timeFrame: 1 month
Secondary outcomes:
measure: Deaths (all-cause mortality) at 1 month
timeFrame: 1 month
measure: Deaths (all-cause mortality) at 1 year
timeFrame: 1 year
measure: Deaths (all-cause mortality) at 2 years
timeFrame: 2 years
measure: Deaths (all-cause mortality) at 3 years
timeFrame: 3 years
measure: Deaths (all-cause mortality) at 4 years
timeFrame: 4 years
measure: Deaths (all-cause mortality) at 5 years
timeFrame: 5 years
measure: All Stroke (disabling and non-disabling) at 1 month
timeFrame: 1 month
measure: All Stroke (disabling and non-disabling) at 1 year
timeFrame: 1 year
measure: All Stroke (disabling and non-disabling) at 2 years
timeFrame: 2 years
measure: All Stroke (disabling and non-disabling) at 3 years
timeFrame: 3 years
measure: All Stroke (disabling and non-disabling) at 4 years
timeFrame: 4 years
measure: All Stroke (disabling and non-disabling) at 5 years
timeFrame: 5 years
measure: Rate of New permanent pacemaker implantation at 1 month
timeFrame: 1 month
measure: Rate of New permanent pacemaker implantation at 1 year
timeFrame: 1 year
measure: Rate of New permanent pacemaker implantation at 2 years
timeFrame: 2 years
measure: Rate of New permanent pacemaker implantation at 3 years
timeFrame: 3 years
measure: Rate of New permanent pacemaker implantation at 4 years
timeFrame: 4 years
measure: Rate of New permanent pacemaker implantation at 5 years
timeFrame: 5 years
measure: Rate of Moderate or severe prosthetic valve regurgitation at 1 month
timeFrame: 1 month
measure: Rate of Moderate or severe prosthetic valve regurgitation at 1 year
timeFrame: 1 year
measure: Rate of Moderate or severe prosthetic valve regurgitation at 2 years
timeFrame: 2 years
measure: Rate of Moderate or severe prosthetic valve regurgitation at 3 years
timeFrame: 3 years
measure: Rate of Moderate or severe prosthetic valve regurgitation at 4 years
timeFrame: 4 years
measure: Rate of Moderate or severe prosthetic valve regurgitation at 5 years
timeFrame: 5 years
measure: Re-hospitalization for signs and symptoms of aortic valve disease and/or THV related complications at 1 month
timeFrame: 1 month
measure: Re-hospitalization for signs and symptoms of aortic valve disease and/or THV related complications at 1 year
timeFrame: 1 year
measure: Re-hospitalization for signs and symptoms of aortic valve disease and/or THV related complications at 2 years
timeFrame: 2 years
measure: Re-hospitalization for signs and symptoms of aortic valve disease and/or THV related complications at 3 years
timeFrame: 3 years
measure: Re-hospitalization for signs and symptoms of aortic valve disease and/or THV related complications at 4 years
timeFrame: 4 years
measure: Re-hospitalization for signs and symptoms of aortic valve disease and/or THV related complications at 5 years
timeFrame: 5 years
measure: Rate of alternating valve of prosthetic valve size during TAVR
timeFrame: peri-procedural
measure: Rate of valve malposition
timeFrame: peri-procedural
measure: Rate of TAV-in-TAV deployment
timeFrame: peri-procedural
measure: Rate of device recapture or retrieval
timeFrame: peri-procedural
measure: Rate of conversion to open surgery
timeFrame: peri-procedural
measure: Rate of unplanned use of cardiopulmonary bypass (CPB) for hemodynamic support at any time during the TAVR procedure
timeFrame: peri-procedural
measure: Rate of coronary obstruction
timeFrame: peri-procedural
measure: Major vascular complications (VARC 2)
timeFrame: peri-procedural
measure: Rate of annulus rupture
timeFrame: peri-procedural
measure: Rate of structural valve deterioration at 1 month
timeFrame: 1 month
measure: Rate of structural valve deterioration at 1 year
timeFrame: 1 year
measure: Rate of structural valve deterioration at 2 years
timeFrame: 2 years
measure: Rate of structural valve deterioration at 3 years
timeFrame: 3 years
measure: Rate of structural valve deterioration at 4 years
timeFrame: 4 years
measure: Rate of structural valve deterioration at 5 years
timeFrame: 5 years
measure: New onset complete LBBB before discharge
timeFrame: before discharge
measure: New onset complete LBBB at 1 month
timeFrame: 1 month
measure: Kansas City Cardiomyopathy Questionnaire (KCCQ) QoL Scores at Baseline
timeFrame: Baseline
measure: Kansas City Cardiomyopathy Questionnaire (KCCQ) QoL Scores at 1 month
timeFrame: 1 month
measure: Kansas City Cardiomyopathy Questionnaire (KCCQ) QoL Scores at 1 year
timeFrame: 1 year
measure: Kansas City Cardiomyopathy Questionnaire (KCCQ) QoL Scores at 2 years
timeFrame: 2 years
measure: Kansas City Cardiomyopathy Questionnaire (KCCQ) QoL Scores at 3 years
timeFrame: 3 years
measure: Kansas City Cardiomyopathy Questionnaire (KCCQ) QoL Scores at 4 years
timeFrame: 4 years
measure: Kansas City Cardiomyopathy Questionnaire (KCCQ) QoL Scores at 5 years
timeFrame: 5 years
measure: New York Heart Association (NYHA) Functional Class at baseline
timeFrame: Baseline
measure: New York Heart Association (NYHA) Functional Class at 1 month
timeFrame: 1 month
measure: New York Heart Association (NYHA) Functional Class at 1 year
timeFrame: 1 year
measure: New York Heart Association (NYHA) Functional Class at 2 years
timeFrame: 2 years
measure: New York Heart Association (NYHA) Functional Class at 3 years
timeFrame: 3 years
measure: New York Heart Association (NYHA) Functional Class at 4 years
timeFrame: 4 years
measure: New York Heart Association (NYHA) Functional Class at 5 years
timeFrame: 5 years
measure: Six Minute Walk Test (6MWT Distance or 6MWD) at baseline
timeFrame: Baseline
measure: Six Minute Walk Test (6MWT Distance or 6MWD) at 1 month
timeFrame: 1 month
measure: Six Minute Walk Test (6MWT Distance or 6MWD) at 1 year
timeFrame: 1 year
measure: Six Minute Walk Test (6MWT Distance or 6MWD) at 2 years
timeFrame: 2 years
measure: Six Minute Walk Test (6MWT Distance or 6MWD) at 3 years
timeFrame: 3 years
measure: Six Minute Walk Test (6MWT Distance or 6MWD) at 4 years
timeFrame: 4 years
measure: Six Minute Walk Test (6MWT Distance or 6MWD) at 5 years
timeFrame: 5 years
measure: Mini-Mental State Examination score at baseline
timeFrame: baseline
measure: Mini-Mental State Examination score at 1 month
timeFrame: 1 month
measure: Mini-Mental State Examination score at 1 year
timeFrame: 1 year
measure: Mini-Mental State Examination score at 2 years
timeFrame: 2 years
measure: Mini-Mental State Examination score at 3 years
timeFrame: 3 years
measure: Mini-Mental State Examination score at 4 years
timeFrame: 4 years
measure: Mini-Mental State Examination score at 5 years
timeFrame: 5 years
measure: Modified Rankin Scale Score at baseline
timeFrame: baseline
measure: Modified Rankin Scale Score at 1 month
timeFrame: 1 month
measure: Modified Rankin Scale Score at 1 year
timeFrame: 1 year
measure: Modified Rankin Scale Score at 2 years
timeFrame: 2 years
measure: Modified Rankin Scale Score at 3 years
timeFrame: 3 years
measure: Modified Rankin Scale Score at 4 years
timeFrame: 4 years
measure: Modified Rankin Scale Score at 5 years
timeFrame: 5 years
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The First affiliated hospital of bengbu medical college
state: Anhui
city: Beijing
country: China
facility: The General Hospital of the People's Liberation Army
state: Beijing
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Xiamen
country: China
facility: Xiamen University Affiliated Cardiovascular Hospital
state: Fujian
city: Guangzhou
country: China
facility: Guangdong People's Hospital
state: Guangdong
city: Zhengzhou
country: China
facility: Zhengzhou Cardiovascular Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Zhengzhou
country: China
facility: Hennan Provincial Chest Hospital
state: Hennan
city: Wuhan
country: China
facility: Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
state: Hubei
city: Changsha
country: China
facility: The Second XIANGYA Hospital Of Central South University
state: Hunan
city: Yangzhou
country: China
facility: Northern Jiangsu People's Hospital
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Nanchang
country: China
facility: The Second Affiliated Hospital of Nanchang University
state: Jiangxi
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
state: Shandong
city: Taiyuan
country: China
facility: Shanxi Cardiovascular Hospital
state: Shanxi
city: Tianjing
country: China
facility: tianjin Chest Hospital
state: Tianjing
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: