AVJ-514 Japan Trial

Not Applicable

Completed

Conditions: Mitral Valve Incompetence
Mitral Stenosis With Insufficiency
Functional Mitral Regurgitation
Mitral Valve Regurgitation
Mitral Insufficiency

Interventions: Device: AVJ-514

Registration Number: NCT02520310

Lead Sponsor: Abbott Medical Devices

Brief Summary: The objective of the study is to confirm the reproducibility of the evidence of safety and efficacy of AVJ-514 System technology in Japanese subjects who have been deemed difficult for mitral valve surgery by the local site heart team.

Detailed Description: This study is a prospective, multi-center, single-arm clinical evaluation of the AVJ-514 System for the treatment of symptomatic chronic severe mitral regurgitation (MR) in Japanese subjects deemed difficult for mitral valve surgery by the local site heart team.

Patients will be evaluated at baseline, discharge, 30 days, 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years in Japanese Medical Centers.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 30

Inclusion Criteria

Subjects must meet all of the following inclusion criteria:

Age 20 years or older.
Symptomatic moderate-to-severe (3+) or severe MR (4+) chronic Degenerative Mitral Regurgitation (DMR) or Functional Mitral Regurgitation (FMR) determined by assessment of a qualifying transthoracic echocardiogram (TTE) obtained within 90 days and transesophageal echocardiogram (TEE) obtained within180 days prior to subject registration, with MR severity based principally on the TTE study and confirmed by the Echocardiography Core Laboratory (ECL). The ECL may request a TEE.
Left Ventricular Ejection Fraction (LVEF) is ≥ 30％ within 90 days prior to subject registration, assessed by the site using any one of the following methods: echocardiography, contrast left ventriculography, gated blood pool scan or cardiac magnetic resonance imaging (MRI). Note: The method must provide a quantitative readout (not a visual assessment).
New York Heart Association (NYHA) classification is class II, class III, or ambulatory class IV.
Subject is deemed difficult for mitral valve surgery due to either Society of Thoracic Surgery (STS) surgical mortality risk for mitral valve replacement of ≥ 8% OR due to the presence of one of the following risk factors:
- Porcelain aorta or mobile ascending aortic atheroma
- Post-radiation mediastinum
- Previous mediastinitis
- Functional MR with LVEF < 40%
- Over 75 years old with LVEF < 40%
- Re-operation with patent grafts
- Two or more prior cardiothoracic surgeries
- Hepatic cirrhosis
- Other surgical risk factor(s)
Mitral valve area ≥ 4.0 cm2 assessed by ECL based TTE within 90 days prior to subject registration. The ECL may request a TEE.
Left Ventricular End Systolic Dimension (LVESD) is ≤ 60mm assessed by site based on the TTE obtained within 90 days prior to subject registration.
The primary regurgitant jet is non-commissural based on TEE, and in the opinion of the AVJ-514 implanting investigator can successfully be treated by the AVJ-514. If a secondary jet exists, it must be considered clinically insignificant.
Transseptal catheterization and femoral vein access is determined to be feasible by the treating physician.
The subject or the subject's legal representative has been informed of the nature of the study and agrees to its provisions and has provided written informed consent as approved by the Institutional Review Board of the respective clinical site.

Exclusion Criteria

Subjects must not meet any of the following exclusion criteria:

LVEF is < 30%
Leaflet anatomy which may preclude AVJ-514 implantation, proper positioning on the leaflets or sufficient reduction in MR by the AVJ-514 based. This evaluation is based on TEE evaluation of the mitral valve within 180 days prior to subject registration and includes:
- Insufficient mobile leaflet available for grasping with the AVJ-514 device
- Lack of both primary and secondary chordal support in the grasping area
- Evidence of significant calcification in the grasping area
- Presence of a significant cleft in the grasping area
Life expectancy < 1 year due to associated non-cardiac co-morbid conditions
Need for emergent or urgent surgery for any reason
Prior open heart mitral valve leaflet surgery or any currently implanted prosthetic mitral valve or any prior transcatheter mitral valve procedure.
Echocardiographic evidence of intracardiac mass, thrombus or vegetation.
Active endocarditis or active rheumatic heart disease or leaflets degenerated from rheumatic disease (i.e. noncompliant, perforated).
Untreated clinically significant coronary artery disease requiring revascularization or significant myocardial ischemia or evidence of an acute myocardial infarction in the prior 90 days of registration.
Cerebrovascular accident within 180 days prior to registration
Severe symptomatic carotid stenosis (> 70% by ultrasound)
Any cardiac surgery within 180 days prior to registration
Percutaneous coronary intervention (PCI) within the last 30 days prior to registration
Implant of Cardiac Resynchronization Therapy (CRT), Cardiac Resynchronization Therapy with Cardioverter Defibrillator (CRT-D) pacemaker or Implantable Cardioverter Defibrillator (ICD)within the last 30 days prior to registration.
Transcatheter aortic valve replacement (TAVR) within the last 30 days prior to registration.
Severe tricuspid regurgitation or aortic valve disease requiring surgical treatment.
In the judgment of the Investigator, the femoral vein cannot accommodate a 24 F catheter or presence of ipsilateral deep vein thrombosis (DVT).
Hemodynamic instability defined as systolic pressure < 90 mmHg without afterload reduction drug or cardiogenic shock or intra-aortic balloon pump.
History of bleeding diathesis or coagulopathy or subject will refuse blood transfusions.
Active infections requiring current antibiotic therapy (if temporary illness, patients may enroll at least 14 days after discontinuation of antibiotics). Patients must be free from infection prior to treatment. Any required dental work should be completed a minimum of 21 days prior to treatment.
Intravenous drug abuse or suspected inability to adhere to follow-up.
Patients in whom TEE is contraindicated.
A known hypersensitivity or contraindication to study or procedure medications which cannot be adequately managed medically.
In the judgment of the Investigator, subjects in whom the presence of a permanent pacemaker or pacing leads would interfere with placement of the test device or the placement of the test device would disrupt the leads.
Subject intends to participate in any other investigational or invasive clinical study within a period of 1 year following the AVJ-514 procedure.
Currently participating in an investigational drug or another device study that has not completed the primary endpoint or that clinically interferes with the current study endpoints. (Note: Trials requiring extended follow-up for products that were investigational, but have since become commercially available, are not considered investigational trials).
In the opinion of the investigator or designee, subject is unable to comply with the requirements of the study protocol or is unsuitable for the study for any reason.
In the opinion of the anesthesiologist, general anesthesia is contraindicated.
Pregnant or planning pregnancy within next 1 year.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
AVJ-514	AVJ-514	The AVJ-514 system

Primary Outcome Measures

Name	Time	Method
Number of Participants With Acute Procedure Success (APS)	On day 0 (the day of procedure)	APS is defined as successful implantation of the AVJ-514 device(s) with resulting MR severity of 2+ or less as determined by the Echocardiographic Core Laboratory (ECL) assessment of a discharge echocardiogram. Subjects who die or who undergo mitral valve surgery before discharge are an APS failure.

Secondary Outcome Measures

Name	Time	Method
All-cause Mortality	5 years
MR Severity Grade	5 years
Cardiac Index (CI)	5 years
Percentage of Participants With Major Adverse Events (MAE) at 30 Days	30 days	MAE is a composite of death, stroke, myocardial infarction (MI), renal failure, and non-elective cardiovascular surgery for device or procedure related adverse events occurring after the femoral vein puncture for transseptal access. This outcome measure calculates the percentage of participants with MAE at 30 days (= total subjects with MAE/total subjects enrolled).
Percentage of Participants With MAE at 1 Year	1 year	MAE is a composite of death, stroke, myocardial infarction (MI), renal failure, and non-elective cardiovascular surgery for device or procedure related adverse events occurring after the femoral vein puncture for transseptal access. This outcome measure calculates the percentage of participants with MAE at 30 days (= total subjects with MAE/total subjects enrolled).
Number of Participants With MAE Occurring After the Femoral Vein Puncture for Transseptal Access	30 days	MAE listed below will be adjudicated by the Clinical Events Committee at 30 days: * Death * Stroke * Myocardial infarction * Renal failure * Non-elective cardiovascular surgery for device or procedure related adverse events
Number of Participants With Mitral Valve Stenosis Requiring Surgery	1 year	Defined as a mitral valve orifice of less than 1.5 cm\^2 as measured by the Echocardiography Core Laboratory.
Number of Participants With Mitral Valve Stenosis Not Requiring Surgery	1 year	Defined as a mitral valve orifice of less than 1.5 cm\^2 as measured by the Echocardiography Core Laboratory.
Number of Participants With Single Leaflet Device Attachment (SLDA) Requiring Surgery	1 year	SLDA is defined as attachment of one mitral valve leaflet to the AVJ-514 device.
Number of Participants With Single Leaflet Device Attachment (SLDA) Not Requiring Surgery	1 year	SLDA is defined as attachment of one mitral valve leaflet to the AVJ-514 device.
Number of Participants With Iatrogenic Atrial Septal Defect	30 days	Defined as defect ('hole') in the septum between the left and right atria; considered clinically significant if it requires percutaneous or surgical intervention.
Percentage of Participants With Device Implant Rate	On the day of procedure	Defined as the rate of successful delivery and deployment of one or more AVJ-514 device with echocardiographic evidence of leaflet approximation and retrieval of the delivery catheter.
Device Procedure Time	On the day of procedure	Defined as the time elapsed from the start of the transseptal procedure to the time the Steerable Guide Catheter is removed.
Total Procedure Time	On the day of procedure	Defined as the time elapsed from the first of any of the following: intravascular catheter placement, anesthesia or sedation, or transesophageal echocardiogram (TEE), to the removal of the last catheter and TEE.
Device Time	On the day of procedure	Defined as the time the Steerable Guide Catheter is placed in the intra-atrial septum until the time the AVJ-514 Delivery System (CDS) is retracted into the Steerable Guide Catheter.
Fluoroscopy Duration	On the day of procedure	Defined as the duration of exposure to fluoroscopy during the AVJ-514 procedure.
Length of Stay in Intensive Care Unit (ICU)/Critical Care Unit (CCU)/Post-Anesthesia Care Unit (PACU) (ICU/CCU/PACU)	At Discharge (≤ 14.4 ± 8.5 days post index procedure)	Length of stay in ICU/CCU/PACU is cumulative hours of Hospital stay in (PACU/CCU/ICU)
Length of Hospital Stay Excluding Rehabilitation Stay	At Discharge (≤ 14.4 ± 8.5 days post index procedure)	Length of hospital stay excluding rehabilitation stay = Length of hospital stay (Date of Discharge - Date of Admission)
Length of Rehabilitation Stay	At Discharge (≤ 14.4 ± 8.5 days post index procedure)	Cumulative days of rehabilitation stay during hospitalization.
Number of Participants With MR Severity Grade	1 year	Mitral regurgitation severity is determined based on the American Society of Echocardiography (ASE) Recommendations for Evaluation of The Severity of Native Valvular Regurgitation with Two-Dimensional and Doppler Echocardiography. MR severity grade was assessed by the core lab using the transthoracic echocardiogram (TTE) at baseline, discharge and subsequent follow-up visits. The severity of MR is determined by the amount of blood being pushed back into the left atrium when it should be circulating through the left ventricle with each heart beat. MR severity is typically classified as mild (grade 1+), moderate (grade 2+), moderate to severe (grade 3+) or severe (grade 4+).
Regurgitant Volume (RV)	5 years
Percentage of Participants With Discharge Status	At Discharge (≤ 14.4 ± 8.5 days post index procedure)	Location to which subject was discharged (home or another facility).
Length of Stay (Not at Baseline Facility)	At Discharge (≤ 14.4 ± 8.5 days post index procedure)	If subject discharged to another facility (different from baseline facility), length of stay at facility to which subject was discharged. Length of Stay (not at baseline facility) = Sum for all eligible log lines which had been entered in Electronic Data Capture (EDC) for ICU/CCU/PACU and rehabilitation.
Number of Participants With Mitral Regurgitation (MR) Severity Grade	At baseline (Within 14 days prior to the AVJ-514 procedure)	Mitral regurgitation severity is determined based on the American Society of Echocardiography (ASE) Recommendations for Evaluation of The Severity of Native Valvular Regurgitation with Two-Dimensional and Doppler Echocardiography. MR severity grade was assessed by the core lab using the transthoracic echocardiogram (TTE) at baseline, discharge and subsequent follow-up visits. The severity of MR is determined by the amount of blood being pushed back into the left atrium when it should be circulating through the left ventricle with each heart beat. MR severity is typically classified as mild (grade 1+), moderate (grade 2+), moderate to severe (grade 3+) or severe (grade 4+).
Regurgitant Fraction (RF)	4 year	Regurgitant fraction as determined by the site. Regurgitant fraction is defined as the regurgitant volume divided by the forward stroke volume through the regurgitant valve.
Left Ventricular End Diastolic Volume (LVEDV)	5 years
Left Ventricular End Systolic Volume (LVESV)	5 years
Left Ventricular End Diastolic Dimension (LVEDD)	5 years
Left Ventricular End Systolic Dimension (LVESD)	5 years
Left Ventricular Ejection Fraction (LVEF)	5 years
Pulmonary Artery Systolic Pressure (PASP)	5 years	Pulmonary Artery Systolic Pressure (PASP) is presented in place of Right Ventricular Systolic Pressure (RVSP). PASP is equal to RVSP in the absence of pulmonic stenosis.
Mitral Valve Area (MVA)	5 years
Mitral Valve Area(MVA)	1 year	It is the orifice area of the mitral valve.
Mean Mitral Valve Pressure Gradient (MVG)	5 years
Number of Participants With Systolic Anterior Motion of the Mitral Valve (Present or Absent)	1 year	Systolic Anterior Motion (SAM) of the mitral valve is measured by the ECL
Systolic Anterior Motion of the Mitral Valve (Present or Absent)	5 years
Forward Stroke Volume (FSV)	5 years
Cardiac Output (CO)	5 years
Number of Participants With All-cause Mortality	1 year
Number of Participants With the Primary Safety Composite of MAE at 1 Year	12 months	MAE is a composite of death, stroke, MI, renal failure, and non-elective cardiovascular surgery for device or procedure related adverse events occurring after the femoral vein puncture for transseptal access. No of Participants with the MAEs at 12 months. One death and One Renal Failure was reported in two subjects.
Freedom From the Components of the Primary Safety Composite of MAE	5 years	MAE is a composite of death, stroke, MI, renal failure, and non-elective cardiovascular surgery for device or procedure related adverse events occurring after the femoral vein puncture for transseptal access.
Number of Patients With New York Heart Association (NYHA) Functional Class	At baseline (Within 14 days prior to the AVJ-514 procedure)	Class I: Patients with cardiac disease but without resulting limitations of physical activity. Class II: Patients with cardiac disease resulting in slight limitation of physical activity. Patients are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain. Class III: Patients with cardiac disease resulting in marked limitation of physical activity. Patients are comfortable at rest. Less than ordinary physical activity causes fatigue, palpitation dyspnea, or anginal pain. Class IV: Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.
Number of Participants With NYHA Functional Class	1 year	Class I: Patients with cardiac disease but without resulting limitations of physical activity. Class II: Patients with cardiac disease resulting in slight limitation of physical activity. Patients are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain. Class III: Patients with cardiac disease resulting in marked limitation of physical activity. Patients are comfortable at rest. Less than ordinary physical activity causes fatigue, palpitation dyspnea, or anginal pain. Class IV: Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.
NYHA Functional Class	5 years	Class I: Patients with cardiac disease but without resulting limitations of physical activity. Class II: Patients with cardiac disease resulting in slight limitation of physical activity. Patients are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain. Class III: Patients with cardiac disease resulting in marked limitation of physical activity. Patients are comfortable at rest. Less than ordinary physical activity causes fatigue, palpitation dyspnea, or anginal pain. Class IV: Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.
Kansas City Cardiomyopathy Questionnaire Quality of Life (KCCQ QoL) Scores	At baseline (Within 14 days prior to the AVJ-514 procedure)	KCCQ is a self-administered questionnaire that quantifies physical limitations, symptoms, self-efficacy, social interference and quality of life. This questionnaire is a reliable and responsive health status measure used in various cardiovascular research studies. A minimum mean group difference in KCCQ score of ≥5 is considered to be clinically significant. Each question responses are coded sequentially (1, 2, 3, 4, 5 and 6) from worst to best status. Scores are generated by adding points for all questions and scaled from 0 to 100, with 0 denoting the worst and 100 the best possible status.
KCCQ QoL Scores	5 years	The Kansas City Cardiomyopathy Questionnaire is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life.
Change in KCCQ QoL Scores From Baseline to 1 Year	Baseline to 1 Year	KCCQ is a self-administered questionnaire that quantifies physical limitations, symptoms, self-efficacy, social interference and quality of life. This questionnaire is a reliable and responsive health status measure used in various cardiovascular research studies. A minimum mean group difference in KCCQ score of ≥5 is considered to be clinically significant. Each question responses are coded sequentially (1, 2, 3, 4, 5 and 6) from worst to best status. Scores are generated by adding points for all questions and scaled from 0 to 100, with 0 denoting the worst and 100 the best possible status.
SF-36 QoL Scores	24 months	The Short Form (36) Health Survey is a 36-item, patient-reported survey of patient health. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Change in SF-36 QoL Scores From Baseline to 1 Year	From baseline to 1 year
Change in SF-36 QoL Scores From Baseline	At 24 months
Number of Participants Undergoing Mitral Valve Surgery	Through 5 years
Number of Participants With Additional Mitra Clip Device Intervention	Through 5 years
Six Minute Walk Test (6MWT) Distance	5 years	The 6MWT is a practical simple test that requires a 100-ft hallway but no exercise equipment or advanced training for technicians. This test measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes (the 6MWD). It evaluates the global and integrated responses of all the systems involved during exercise, including the pulmonary and cardiovascular systems, systemic circulation, peripheral circulation, blood, neuromuscular units, and muscle metabolism. It does not provide specific information on the function of each of the different organs and systems involved in exercise or the mechanism of exercise limitation, as is possible with maximal cardiopulmonary exercise testing. The self-paced 6MWT assesses the submaximal level of functional capacity.
Changes in Six Minute Walk Test (6MWT) Distance From Baseline to 1 Year	Baseline to 1 year
Changes in Six Minute Walk Test (6MWT) Distance From Baseline	At 24 months
Number of Participants With Mitral Valve Surgery	1 year	Surgical access to repair or replace the mitral valve. Measured per occurrence.
Number of Participants With Additional AVJ-514 Device Intervention	1 year	Number of participants with any additional AVJ-514 procedure after the index procedure. Measured per occurrence.
Mitral Stenosis	5 years	Defined as a mitral valve orifice of less than 1.5 cm2 as measured by the Echocardiography Core Laboratory.
Number of Hospitalizations and Reason for Hospitalization	1 year post index procedure
Number of Hospitalizations	5 years
Number of Participants With Mitral Stenosis	1 year	Defined as a mitral valve orifice of less than 1.5 cm2 as measured by the Echocardiography Core Laboratory.
Number of Participants With Clinically Significant Atrial Septal Defect (ASD) That Requires Intervention	12 months	Defect ('hole') in the septum between the left and right atria; considered clinically significant if it requires percutaneous or surgical intervention (repair of ASD completed at the time of surgery for other reasons, but not as the primary reason for surgery, is not counted as ASD.)
Number of Participants With Clinically Significant ASD That Requires Intervention	5 years	Defect ('hole') in the septum between the left and right atria; considered clinically significant if it requires percutaneous or surgical intervention (repair of ASD completed at the time of surgery for other reasons, but not as the primary reason for surgery, is not counted as ASD.)
Number of Participants With Major Bleeding	1 year	Major bleeding is defined as bleeding ≥ Type 3 based on a modified Bleeding Academic Research Consortium (BARC) definition. Type 3: * Type 3a (i) Overt bleeding plus hemoglobin drop of 3 to \<5 g/dL\* (provided hemoglobin drop is related to bleed) (ii) Any transfusion with overt bleeding * Type 3b (i) Overt bleeding plus hemoglobin drop ≥5 g/dL\* (provided hemoglobin drop is related to bleed) (ii) Cardiac tamponade (iii) Bleeding requiring surgical intervention for control (excluding dental/nasal/skin/hemorrhoid) (iv) Bleeding requiring intravenous vasoactive agents * Type 3c (i) Intracranial hemorrhage (does not include microbleeds or hemorrhagic transformation, does include intraspinal) (ii) Subcategories confirmed by autopsy or imaging or lumbar puncture (iii) Intraocular bleed compromising vision
Number of Participants With Usage of Concomitant Cardiac Medications	1 year	Number of participants with any change in type of medication from baseline to follow-up. Measured in overall counts.
Rate of Heart Failure Hospitalizations in the 1 Year Post-AVJ-514 Procedure Compared to the 1 Year Prior	1 Year Pre and Post Index Procedure
Number of Participants With Device Embolization Requiring Surgery	1 year	Device embolization is defined as detachment of the deployed AVJ-514 device from both mitral leaflets.
Number of Participants With Device Embolization Not Requiring Surgery	1 year	Device embolization is defined as detachment of the deployed AVJ-514 device from both mitral leaflets.

Trial Locations

Locations (6): Tokyo Women's Medical University Hospital
🇯🇵
Tokyo, Japan
Sakakibara Heart Institute
🇯🇵
Tokyo, Japan
Shonan Kamakura General Hospital
🇯🇵
Kanagawa, Japan
Sendai Kosei Hospital
🇯🇵
Miyagi, Japan
National Cerebral and Cardiovascular Center
🇯🇵
Osaka, Japan
Keio University Hospital
🇯🇵
Tokyo, Japan