HANGZHOU Solution in Bicuspid AS Undergoing TAVR

Second Affiliated Hospital, School of Medicine, Zhejiang University508 enrolled

Overview

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

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

508

Conditions

Aortic Stenosis Aortic Stenosis With Bicuspid Valve

Interventions

TAVR with Venus A plus using supra-annular sizing and THV implantation technique (Hangzhou solution)DEVICE

Transcatheter aortic valve replacement (TAVR) with Venus A plus using supra-annular sizing and THV implantation technique (Hangzhou solution)

TAVR with Venus A plus using annular sizing and THV implantation techniqueDEVICE

Transcatheter aortic valve replacement (TAVR) with Venus A plus using annular sizing and THV implantation technique (Traditional sizing strategy)

Eligibility

Sex: ALLMin age: 60 Years

Medical Language ↔ Plain English

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.

Locations (18)

The First affiliated hospital of bengbu medical college

Bengbu, Anhui, China

Outcomes

Primary Outcomes

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

Composite of all-cause mortality, disabling stroke, new permanent pacemaker implantation and moderate or severe prosthetic valve regurgitation at 1 month (per Valve Academic Research Consortium-2 \[VARC-2\] criteria)

Time frame: 1 month

Secondary Outcomes

Deaths (all-cause mortality) at 1 month

Number of deaths from any cause mortality at 1 month

Time frame: 1 month

Deaths (all-cause mortality) at 1 year

Time frame: 1 year

Deaths (all-cause mortality) at 2 years

Time frame: 2 years

Deaths (all-cause mortality) at 3 years

Time frame: 3 years

Deaths (all-cause mortality) at 4 years

Time frame: 4 years

Deaths (all-cause mortality) at 5 years

Time frame: 5 years

All Stroke (disabling and non-disabling) at 1 month

duration of a focal or global neurological deficit \>24 h; OR \<24 h if available neuroimaging documents a new haemorrhage or infarct; OR the neurological deficit results in death

Time frame: 1 month

All Stroke (disabling and non-disabling) at 1 year

Time frame: 1 year

Central Contacts

Jian'an Wang, PhD, MD

CONTACT

+86057187783777 wja@zju.edu.cn

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

The General Hospital of the People's Liberation Army

Beijing, Beijing Municipality, China

NOT_YET_RECRUITING

Fujian Medical University Union Hospital

Fuzhou, Fujian, China

NOT_YET_RECRUITING

Xiamen University Affiliated Cardiovascular Hospital

Xiamen, Fujian, China

NOT_YET_RECRUITING

Guangdong People's Hospital

Guangzhou, Guangdong, China

NOT_YET_RECRUITING

Zhengzhou Cardiovascular Hospital

Zhengzhou, Henan, China

NOT_YET_RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

NOT_YET_RECRUITING

Hennan Provincial Chest Hospital

Zhengzhou, Hennan, China

NOT_YET_RECRUITING

Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology

Wuhan, Hubei, China

RECRUITING

The Second XIANGYA Hospital Of Central South University

Changsha, Hunan, China

NOT_YET_RECRUITING

...and 8 more locations

All Stroke (disabling and non-disabling) at 2 years

Time frame: 2 years

All Stroke (disabling and non-disabling) at 3 years

Time frame: 3 years

All Stroke (disabling and non-disabling) at 4 years

Time frame: 4 years

All Stroke (disabling and non-disabling) at 5 years

Time frame: 5 years

Rate of New permanent pacemaker implantation at 1 month

Rate of New permanent pacemaker implantation (e.g. defibrillator, single vs. dual chamber, biventricular)

Time frame: 1 month

Rate of New permanent pacemaker implantation at 1 year

Time frame: 1 year

Rate of New permanent pacemaker implantation at 2 years

Time frame: 2 years

Rate of New permanent pacemaker implantation at 3 years

Time frame: 3 years

Rate of New permanent pacemaker implantation at 4 years

Time frame: 4 years

Rate of New permanent pacemaker implantation at 5 years

Time frame: 5 years

Rate of Moderate or severe prosthetic valve regurgitation at 1 month

Moderate or severe prosthetic valve regurgitation by transthoracic echocardiography, VARC-2 definition

Time frame: 1 month

Rate of Moderate or severe prosthetic valve regurgitation at 1 year

Time frame: 1 year

Rate of Moderate or severe prosthetic valve regurgitation at 2 years

Time frame: 2 years

Rate of Moderate or severe prosthetic valve regurgitation at 3 years

Time frame: 3 years

Rate of Moderate or severe prosthetic valve regurgitation at 4 years

Time frame: 4 years

Rate of Moderate or severe prosthetic valve regurgitation at 5 years

Time frame: 5 years

Re-hospitalization for signs and symptoms of aortic valve disease and/or THV related complications at 1 month

Re-hospitalization for signs and symptoms of aortic valve disease and/or THV related complications by VARC-2 definition

Time frame: 1 month

Re-hospitalization for signs and symptoms of aortic valve disease and/or THV related complications at 1 year

Time frame: 1 year

Re-hospitalization for signs and symptoms of aortic valve disease and/or THV related complications at 2 years

Time frame: 2 years

Re-hospitalization for signs and symptoms of aortic valve disease and/or THV related complications at 3 years

Time frame: 3 years

Re-hospitalization for signs and symptoms of aortic valve disease and/or THV related complications at 4 years

Time frame: 4 years

Re-hospitalization for signs and symptoms of aortic valve disease and/or THV related complications at 5 years

Time frame: 5 years

Rate of alternating valve of prosthetic valve size during TAVR

Alternating valve of prosthetic valve size during TAVR (up size or down size)

Time frame: peri-procedural

Rate of valve malposition

Valve malposition (migration, embolization, and ectopic deployment)

Time frame: peri-procedural

Rate of TAV-in-TAV deployment

TAV-in-TAV deployment (An additional valve prosthesis is implanted within a previously implanted prosthesis because of suboptimal device position and/or function, during the index procedure)

Time frame: peri-procedural

Rate of device recapture or retrieval

Device recapture or retrieval peri-procedural

Time frame: peri-procedural

Rate of conversion to open surgery

Conversion to open surgery (Conversion to open sternotomy during the TAVR procedure secondary to any procedure-related complications)

Time frame: peri-procedural

Rate of unplanned use of cardiopulmonary bypass (CPB) for hemodynamic support at any time during the TAVR procedure

Unplanned use of cardiopulmonary bypass (CPB) for hemodynamic support at any time during the TAVR procedure

Time frame: peri-procedural

Rate of coronary obstruction

Coronary obstruction (Angiographic or echocardiographic evidence of a new, partial or complete, obstruction of a coronary ostium, either by the valve prosthesis itself, the native leaflets, calcifications, or dissection, occurring during the TAVR procedure)

Time frame: peri-procedural

Major vascular complications (VARC 2)

Major vascular complications by VARC 2 definition

Time frame: peri-procedural

Rate of annulus rupture

Procedural-related injuries occur in the region of the aortic root and the left ventricular outflow tract during transcatheter aortic valve replacement.

Time frame: peri-procedural

Rate of structural valve deterioration at 1 month

Structural valve deterioration (2017 EAPCI/ESC/EACTS definition)

Time frame: 1 month

Rate of structural valve deterioration at 1 year

Time frame: 1 year

Rate of structural valve deterioration at 2 years

Time frame: 2 years

Rate of structural valve deterioration at 3 years

Time frame: 3 years

Rate of structural valve deterioration at 4 years

Time frame: 4 years

Rate of structural valve deterioration at 5 years

Time frame: 5 years

New onset complete LBBB before discharge

New onset complete LBBB, by 2009 AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part III definition

Time frame: before discharge

New onset complete LBBB at 1 month

Time frame: 1 month

Kansas City Cardiomyopathy Questionnaire (KCCQ) QoL Scores at Baseline

The Kansas City Cardiomyopathy Questionnaire is a 23-item, self administered instrument that quantifies physical function, symptoms, social function, self-efficacy and knowledge, and quality of life. with a range of possible subscale scores from 0 to 100, with 100 representing the least burden of symptoms. The KCCQ tool quantifies the following six (6) distinct domains and two (2) summary scores: KCCQ Symptom Domain, KCCQ Physical Function Domain, KCCQ Quality of Life Domain, KCCQ Social Limitation Domain, KCCQ Self-efficacy Domain, KCCQ Symptom Stability Domain, Clinical Summary Score and Overall Summary Score. Clinical Summary Score includes total symptom and physical function scores to correspond with NYHA Classification. Overall Summary Score includes the total symptom, physical function, social limitations and quality of life scores.

Time frame: Baseline

Kansas City Cardiomyopathy Questionnaire (KCCQ) QoL Scores at 1 month

Time frame: 1 month

Kansas City Cardiomyopathy Questionnaire (KCCQ) QoL Scores at 1 year

Time frame: 1 year

Kansas City Cardiomyopathy Questionnaire (KCCQ) QoL Scores at 2 years

Time frame: 2 years

Kansas City Cardiomyopathy Questionnaire (KCCQ) QoL Scores at 3 years

Time frame: 3 years

Kansas City Cardiomyopathy Questionnaire (KCCQ) QoL Scores at 4 years

Time frame: 4 years

Kansas City Cardiomyopathy Questionnaire (KCCQ) QoL Scores at 5 years

Time frame: 5 years

New York Heart Association (NYHA) Functional Class at baseline

Measure Description: The New York Heart Association (NYHA) Classification provides a simple way of classifying the extent of heart failure. It classifies patients in one of four categories based on their limitations during physical activity:Class I: No symptoms and no limitation in ordinary physical activity Class II: Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity Class III: Marked limitation in activity due to symptoms Class IV: Severe limitations

Time frame: Baseline

New York Heart Association (NYHA) Functional Class at 1 month

Time frame: 1 month

New York Heart Association (NYHA) Functional Class at 1 year

Time frame: 1 year

New York Heart Association (NYHA) Functional Class at 2 years

Time frame: 2 years

New York Heart Association (NYHA) Functional Class at 3 years

Time frame: 3 years

New York Heart Association (NYHA) Functional Class at 4 years

Time frame: 4 years

New York Heart Association (NYHA) Functional Class at 5 years

Time frame: 5 years

Six Minute Walk Test (6MWT Distance or 6MWD) at baseline

Six-Minute Walk Test is a submaximal exercise test that entails measurement of distance walked over a span of 6 minutes. The 6-minute walk test distance (6 MWD) provides a measure for integrated global response of multiple cardiopulmonary and musculoskeletal systems involved in exercise.

Time frame: Baseline

Six Minute Walk Test (6MWT Distance or 6MWD) at 1 month

Time frame: 1 month

Six Minute Walk Test (6MWT Distance or 6MWD) at 1 year

Time frame: 1 year

Six Minute Walk Test (6MWT Distance or 6MWD) at 2 years

Time frame: 2 years

Six Minute Walk Test (6MWT Distance or 6MWD) at 3 years

Time frame: 3 years

Six Minute Walk Test (6MWT Distance or 6MWD) at 4 years

Time frame: 4 years

Six Minute Walk Test (6MWT Distance or 6MWD) at 5 years

Time frame: 5 years

Mini-Mental State Examination score at baseline

The MMSE is scored on a 30-point scale, with items that assess orientation (temporal and spatial; 10 points), memory (registration and recall; 6 points), attention/concentration (5 points), language (verbal and written; 8 points), and visuospatial function (1 point)

Time frame: baseline

Mini-Mental State Examination score at 1 month

Time frame: 1 month

Mini-Mental State Examination score at 1 year

Time frame: 1 year

Mini-Mental State Examination score at 2 years

Time frame: 2 years

Mini-Mental State Examination score at 3 years

Time frame: 3 years

Mini-Mental State Examination score at 4 years

Time frame: 4 years

Mini-Mental State Examination score at 5 years

Time frame: 5 years

Modified Rankin Scale Score at baseline

MODIFIED RANKIN SCALE SCORE DESCRIPTIONS: 0- No symptoms at all; 1- No significant disability despite symptoms; able to carry out all usual duties and activities; 2- Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance; 3- Moderate disability; requiring some help, but able to walk without assistance; 4- Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance; 5- Severe disability; bedridden, incontinent and requiring constant nursing care and attention; 6- Dead

Time frame: baseline

Modified Rankin Scale Score at 1 month

Time frame: 1 month

Modified Rankin Scale Score at 1 year

Time frame: 1 year

Modified Rankin Scale Score at 2 years

Time frame: 2 years

Modified Rankin Scale Score at 3 years

Time frame: 3 years

Modified Rankin Scale Score at 4 years

Time frame: 4 years

Modified Rankin Scale Score at 5 years

Time frame: 5 years